HYDROXAMIC ACID DERIVATIVES FOR USE WITH THE TREATMENT OF DISEASES RELATED TO CONNECTIVE TISSUE DEGRADATION

Abstract: The present invention provides novel hydroxamic acid derivatives represented by the compound of formula (I), or pharmaceutical acceptable salts thereof, wherein the compounds of the present invention inhibit various enzymes from the matrix metalloproteinase family, including collagenase, stromelysin, and gelatinase, and hence are useful for the treatment of matrix metallo endoproteinase diseases such as osteoarthrits, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, and other diseases related to connective tissue degradation.

Description: HYDROXAMIC ACID DERIVATIVES FOR USE WITH THE TREATMENT OF DISEASES RELATED TO CONNECTIVE TISSUE DEGRADATION FIELD OF THE INVENTION 5 The present invention relates to novel hydroxamic acid derivatives or pharmaceutically acceptable salts thereof, their preparation, and pharmaceutical compositions containing them. Particularly, the present invention relates to hydroxamic acid derivatives substituted by a series of 2-pyrrolidinones, hydantions, and pyrazolidinones, which are useful in the treatment of diseases related to connective tissue degradation. BACKGROUND OF THE INVENTION Loss of connective tissue integrity occurs in many disease processes, including osteoarthritis, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth) periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, and other diseases related to connective tissue degradation. Although there is a high incidence of these diseases in the developed world, there is no treatment that prevents the tissue damage that occurs. Considerable lines of scientific evidence indicate that uncontrolled connective matrix metalloproteinase (MMPs) activity is responsible for the damage, and as a consequence the inhibition of these enzymes has become the target for therapeutic intervention (see Matrisian, L. M., Bases, Vol. 14, pp 445-463, (1992); Emonard, H. et al., Cellular and molecular Biology, Vol. 36, pp 131-153, (1990); Docherty, A. J. P. et al., Annals of the Rheumatic, Vol. 49, pp 469-479, (1990)). The compounds of the present invention inhibit various enzymes from the matrix metalloproteinase family, including coUagenase, stromelysin, and gelatinase, and hence are useful for the treatment of matrix metallo endoproteinase diseases such as osteoarthritis, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, and other diseases related to connective tissue degradation. These compounds may also inhibit the release of cytokines including tumor necrosis factor (TNFα) and hence may also be useful in the treatment of inflammation, fever, acute infections and shock. INFORMATION DISCLOSURE International PubUcation No. WO95/09841 discloses new hydroxamic acid derivatives of amino acid amide compounds useful as TNF release and matrix metalloprotease inhibitors, e.g., for treating inflammation, fever or arthritis. International PubUcation No. O95/04033-A1 discloses new succinimide derivatives useful as gelatinase and coUagenase inhibitors. International PubUcation No. W093/21942 discloses matrix metaUo protease inhibitors for promoting tumour regression by inhibiting cancer ceU proUferation and angiogenesis, atherosclerosis, ovarian carcinoma, melanoma and sarcoma. European Patent Publication 0,574,758A discloses new hydroxamic acid derivatives useful as coUagenase inhibitors for the treatment of arthritis, tumours, atherosclerosis, etc. UK Patent AppUcation GB2,282,598A discloses hydroxysuccinyl hydroxyamines useful in the prophylaxis or treatment of diseases or conditions mediated by metaUoproteinases and/or tumour necrosis factor. SUMMARY OF THE INVENTION The present invention provides novel hydroxamic acid derivatives represented by the formula I: with the proviso that when X is -NR 5 - then Y is -(CH 2 )-; d) -C(=0)NH(CH 2 ) k NR 6 R 7 , e) -C(=0)NH(CH 2 ) j -Aryl, f) -C(=0)NH(CH 2 ) k -O-(CH 2 ) k NR 6 R 7 , g) -C(=0)NH(CH 2 ) k -S-(CH 2 ) j NRgR 7 , h) -C(=0)NH(CH 2 ) k -NHS0 2 -Aryl, i) C(=O)NH(CH 2 ) k -NHSO 2 -NR 6 R 7 , or R κ is a) H, b) C^g alkyl, c) -(CH 2 ) j -Aryl, d) -(CH 2 ) j -Aryl - Aryl, e) -(CH 2 )j -Aryl -(CH^j -Aryl, f) (CH 2 )j -Het, or g) -(CH 2 ) j -cycloalkyl Rg and R 7 may be the same or differently a) H, b) C^g alkyl, c) -(CH 2 )j -Aryl, d) Q, or e) Rg and R 7 taken together with the Unking N-atom form azetidinyl, pyrroUdinyl, piperazinyl, piperidinyl, or morphoUnyl, optionaUy substituted with one or more C-^ alkyl; g) Aryl is phenyl, optionaUy substituted with one or more of the foUowing: a) halogen, k is 2, 3, or 4; n is 0, 1, 2, 3, or 4; C^ alkyl, C^galkyl, or C j ^r j lkyl in each of the above definitions, may be each and independently substituted with one to three halogen, hydroxy, or cyano; and with the proviso that when R is methylbutyl R 4 is other than H. The present invention provides novel hydroxamic acid derivatives useful as preventatives and therapeutics for diseases related to connective tissue degradation. DETAILED DESCRIPTION OF THE INVENTION For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C j ; defines the number of carbon atoms present from the integer "i" to the integer "j" inclusive. Thus, C j _4 alkyl refers to alkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyl and isomeric forms thereof. The terms "C^g alkyl", "C 1 . 10 alkyl" or "C 1 . 20 alkyl", refers to methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, etc. and isomeric forms thereof, and preferably an alkyl group having 1 to 6 carbon atoms. The C j . alkyl group may optionaUy be substituted by one or more substituents selected from the group consisting of a halogen atom, a hydroxy group, or -CN group such as, for example, fluoromethyl, difiuoromethyl, fluoroethyl, cyanomethyl and the like. The term "Cg_g cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and isomeric forms thereof, and preferably an cycloalkyl group having 4 to 6 carbon atoms. The term "halogen" refers to fluoro, chloro, bromo, or iodo, preferably fluoro and chloro. The term "Q" refers to a saturated 5-, or 6-membered heterocycUc moiety having 1-2 atoms selected from the group consisting of nitrogen, oxygen, and sulfur forming such groups as, for example, dioxolane, imidazoUdine, dithiolane, oxathiolane, oxazoUdine, piperidinyl, piperazinyl, morphoUno and thiomorpholino. The term "Het" refers to a 5-, 6-membered heteroaromatic moiety having one or more atoms selected form the group consisting of nitrogen, oxygen, and sulfur forming such groups as, for example, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 3- pyrazinyl, 2-furanyl, 3-furanyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-pyrazolyl. A preferred heteroaromatic ring within the definition is 2-thienyl and pyridyl. Within the definition of the terms "Het", and "Q", the nitrogen atom forming the hetero rings may have a protective group such as an acetyl or hydroxyacetyl group. The compounds of the present invention can be converted to their salts according to conventional methods. The term "pharmaceutically acceptable salts" refers to salts useful for administering the compounds of this invention and these include hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesylate, maleate, malate, succinate, tartrate, citrate, 2-hydroxyethyl sulfonate, fumarate and the like. These salts may be in hydrated form. Some of the compounds of this invention may form metal salts such as sodium, potassium, calcium and magnesium salts and these are embraced by the term "pharmaceuticaUy acceptable salts". Certain of the hydroxamic acid derivatives of the present invention are preferred. The preferred R j substituent is methylpropyl. The preferred R 2 substituent is H, methyl, 2-(l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl, 2-( l,3-d ιydro-l,3-dioxo-2H-naphthoisoindol-2-yl)ethyl, 2-(4,5,6,7,- tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(5,6,-dichloro-l,3-dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(5-amino-l,3-dihydro-l,3-dioxo-2H-isoindol-2- yDethyl, 2-(4-nitro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(5-nitro-l,3- dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(4-fluoro- l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl, 2-(4,7-difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(5- fluoro- 1,3-dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-( 1,3-dihydro- l,3-dioxo-2H- isoindol-2-yl)propyl, 2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)methyl, 2-(2- thienylthio)propyl, or 2-(2-thienylthio)methyl. The preferred R 3 substituent is H, 2-methylpropyl, cyclohexylmethyl, benzyl, or phenyl. The preferred R 4 substituent is H or acetamide. The preferred absolute configurations of the compounds claimed in the present invention are as represented in the structures II - VII. The absolute configurations are determined under the Cahn-Ingold-Prelog nomenclature system. The compounds depicted in the Examples are racemic unless indicated otherwise by R or S to refer their optical activity. The pure enantiomers possess higher inhibitory activities. The racemic mixtures are useful in the same way and for the same purpose as the pure enantiomer; the difference is that more racemic material may be used to produce the same inhibitory effect. OpticaUy pure material can be obtained by using chiral HPLC methods to provide the corresponding enantiomers as iUustrated in Examples 2, 5, and 28. OptionaUy, opticaUy pure materials can be obtained chemically to provide the desired enantiomer as illustrated in Examples 29- 34. Depending on substituents, the compounds of this invention may exist in geometric, optical and other isomeric forms and this invention embraces any of these isomers or enantiomers. Particularly preferred compounds of this invention are as follows: la) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3- pyrroUdineacetamide, lb) (3S)-N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide, lc) N-Hydroxy-α-methyl-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide, Id) α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, le) (3S)-α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, If) α-[2-( 1,3-Dihydro- l,3-dioxo-2H-naphthoisoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lg) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(4,5,6,7- tetrafluoro-l,3-d ydro-l,3-dioxo-2H-isomdol-2-yl)ethyl]-3-pyrroUd eacetamide, lh) α-[2-(5,6-Dichloro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylprOpyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdmeacetamide, li) α-[2-(5-Amino-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lj ) N-Hydroxy-3-(2-methylpropyl)-α-[2-(4-nitro- 1,3-dihydro- 1 ,3-dioxo-2H- isoindol-2-yl)ethyl]-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, Ik) N-Hydroxy-3-(2-methylpropyl)-α-[2-(5-nitro-l,3-dihydro-l,3-dioxo-2H- isomdol-2-yl)ethyl]-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 11) α-[2-(4-Fluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3- ( 2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lm) α-[2-(4,7-Difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, In) α-[2-(5-Fluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lo) α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)propyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lp) α-[2-( l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)methyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lq) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(2- thienylthio)ethyl]-3-pyrroUdineacetamide, lr) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(2- thienylthio)propyl]-3-pyrroUdineacetamide, Is) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(2- t-bJenylthio)methyl]-3-pyrroUdineacetamide, It) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-l,3- pyrroUdinediacetamide , lu) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- 1,3-pyrroUdinediacetamide, lv) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-3- pyrroUdineacetamide, lw) α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo- l-(phenylmethyl)-3-pyrroUdineacetamide, lx) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-α-[2-(4,5,6,7- tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, ly) l-(3-Fluorophenyl)methyl)-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, lz) α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N 3 -hydroxy-N 1 - methyl-3-(2-methylpropyl)-2-oxo-l,3-pyπOUdinediacetamide, 2a) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 3 -t2-(4,5,6,7- tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-l,3-pyrroUdinediacetamide, 2b) [S-(R* , R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetaπ-ide, 2c) [S,R-(R*, R*)]-α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N 3 - hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide , 2d) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)- 1,3-pyττoUdinediacetamide , 2e) [S-(R*, R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -(2-phenethyl)-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2f) [S-(R*. R*)]-N 3 -Hydroxy-N 1 -methyl-α 1 ,3-bis (2-methylpropyl)-2-oxo- 1,3-pyrroUdinediacetamide, 2g) [S-(R*, R*)]-α 1 -(Cyclohexylmethyl)-N 3 -hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 2h) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(3-methylbutyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2i) N-Hydroxy-3-(2-methylpropyl)-2,5-dioxo- l-(2-phenylethyl)-3- pyrroUdineacetamide, 2j) N-Hydroxy-3-methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazolidineacetamide, 2k) N-Hydroxy-4-(2-methylpropyl)-2 ,5-dioxo- l-(2-phenylethyl)-4- imidazoUdineacetamide, 21) N-Hydroxyl-4-(2-methylpropyl)-5-oxo-l-(2-phenylethyl)-4- pyrazoUdineacetamide monohydrochloride, 2m) [S-(Λ*Ji*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -phenyl-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2n) [S-(i?* t K*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- Λ^ 1 -(2-p3π^dmylmethyl)-l,3-pyrroUdinediacetamide, 2o) [S-(β* r β*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 2p) [S-(Λ* β *)]-N 1 -(4-Fluorophenyl)-iV 3 -hydroxy-3-(2-methylpropyl)-2-oxo- α -(phenylmethyl)-l,3-pyrrolidinediacetamide, 2q) [S-(Λ* fl*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -[ l-(phenylmethyl)-4-piperdinyl]- 1,3-pyrroUdinediacetamide, 2r) [S-(Λ* τ fi*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N - 4-piperdinyl)-l,3-pyrroUdinediacetamide, 2s) /S-( β *-R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(4-pyridinylmethyl)- 1,3-pyrroUdinediacetamide, 2t ) [S-(Λ* fl*)]-N 1 -(4-Fluorophenylmethyl)-N 3 -hydroxy-3-(2-methylpropyl)- 2-oxo-α -(phenyJmethyl)-l,3-pyrroUdinediacetamide, 2u) [S-(i?*- β *)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(2- phenylethy 1)- 1 ,3-p yrroUdinediacetamide, 2v ) [S-(i2*J?*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-a 1 -(2-phenylethyl)- N -(phenylmethyl)-l,3-pyrroUdinediacetamide, 2w ) [S- ( 2?*J?*)]-N 3 -Hydroxy-a 1 ,3-bis ( 2-methylpropyl)-2-oxo-N 1 -2-pyridinyl- 1,3-pyrτoUdinediacetamide, 2x) tS-(B* r R*)]-α 1 -Cyclohexyl-N 3 -hydroxy-iV 1 -methyl-3-(2-methylpropyl)-2- oxo- 1,3-pyrroUdinediacetamide, 2y) [S-(β* r R*)]-α 1 -Cyclohexyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-iV 1 -2- pvridinyl-l,3-pyrroUdinediacetamide, 2z) [S-(i2*-R*)]-3-(Cyclopentylmethyl)-iV 3 -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 3a) [S-(ie*J?*)]-3-(Cyclopentylmethyl)-iV 3 -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 3b) [3S-[l(β*),3 J R*(β*)]]-α 3 -[2-(Benzoylamino)ethyl]-iV 3 -hydroxy-iV 1 - methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenyl.methyl)-l,3-pvrroUdinediacetamide, 3c) [S-(β*JΪ*)]-N 3 -Hydroxy-3-(2-methylpropyl)-N 1 -[2-(4- morpholinyl)ethyl]-2-oxo-α -(phenylmethyl)-l,3-pyrroUdinediacetamide, 3d) [S-(i?* r R*)]-N-Hydroxy-3-(2-methylpropyl)-l-[2-(4-morphoUnyl)-2-oxo-l- (phenylmethyl)ethyl]-2-oxo-3-pyrroUdineacetamide, 3e) [l( S)-[l[Λ*(β*)], 3α,5α]]-l-[2-(3,5-Dimethyl-l-piperazinyl)-2-oxo-l- (phenylmethyl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 3f) [S-(R* -R* )]-N 3 -Hydroxy-3-(2-methylproρyl)-2-oxo-α 1 -(phenylmethyl)- N 1 -2-pyridinyl-l,3-pyrroUdinediacetamide, 3g) [3S-[l(i?*),3Λ*(β*)]]-α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide, 3h) [S-(i2*JΪ*)3-α 1 -Cyclohexyl-N 1 -cyclopropylmethyl-iV 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 3i) [S-(β* > R*)]-α 1 -Cyclohexyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo- 1, 3-pyrroUdinediacetamide , 3j) [S-(B*,R*)]-a 1 -tert-Butyl-iv '3 -hydroxy-iV 1 -methyl-3-(2-methylpropyl)-2- oxo-l,3-pyrroUdinediacetamide, 3k) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(5- propyloxy-l,3-d ydro-l,3-ό oxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, 31) [R-(R*,S*)]-5-Fluoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrrolidinyl]-l,3-dioxo-2H-isoindole-2-butanamide, 3m) α-[2-(5,6-Difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-iV- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3n) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(5- trifluoromethyl-l,3-dmydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrrolidineacetamide, 3o) α-^-d.S^.δ^ -Hexahydro-l.S-dioxo^H-isoindol^-yDethylJ-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3p) α-[2-(l,3-Dilιydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(3-phenylpropyl)-3-pvrroUdineacetamide, 3q) l-[2-(4-Fluorophenyl)ethyl]-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-iV " -hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 3r) α-[2-(o-benzoic suMr-ude)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetamide, 3s) Ethyl Phenylmethyl [4-(hydroxyamino)-3-[3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdinyl]-4-oxobutyl]imidodicarbonate, 3t) S-(i2* r β*)]-l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyττoUdinyl]-l,3-dioxo-2H-isoindole-2-butanamide, 3u) l,3-D ydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo- 1-[2-(4- fluorophenyl)ethyl]-3-pyrroUdinyl]-l,3-dioxo-2ff-isoindole-2-butanamide, 3v) a-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3w) [R-(R* ,S*)-a-[2-[(3-Fluorobera-zoyl)aniino]ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3x) α-[2-[(4-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3y) N-Hydroxy-3-(2-methylpropyl)-α-[2-[(3-nitrobenzoyl)amino]ethyl]-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, 3z) α-[2-[(3-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pvrroUdineacetamide, 4a) α-[2-[(3-Fluorobenzoyl)amino]ethyl]-l-[2-(4-fluorophenyl)ethyl]--V- hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 4b) α-[2-[(4-Biphenylcarbonyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4c) N-Hydroxy-α-[2-[[(4-methylphenyl)sulfonyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4d) α-[2-[[(4-Fluorophenyl)sulfonyl]amino]ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4e) N-Hydroxy-α-[2-[[(4-methoxyphenyl)sulfonyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4f) N-Hydroxy-3-(2-methylpπ>pyl)-2-oxo- l-(2-phenylethyl)-α-[2- t(phenylsulfonyl)aπuno]ethyl]-3-pyrroUdineacetamide, 4g) [ β -( β *,S*)]-α-[2-[t(4-Fluorophenyl)sulfonyl]amino]ethyl]-N-hydroxy-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pvrroUdineacetamide, 4h) 5,6-Difluoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 4i) l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl ) -2-oxo-l-(2-phenylethyl)-3- pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 4j) [S-(i?*,S*)3-6-Fluoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 4k) [β-(β*,S*)]-5-Fluoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 41) [Λ-(Λ*,S*)]-5,6-Difluoro-l,3-dihydro-iv ' -hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUόinyl]-l-oxo-2H-isoindole-2-butanaπ-ide, 4m) iV-Hydroxy-α-[[[(4-methoxyphenyl)sulfonyl]amino]-methyl]-3-(2- methylpropy l)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide (αR-diastereomer ) , 4n) N-Hydroxy-a-[[[(4-methoxyphenyl)sulfonyl]amino]-methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αS-diastereomer), 4o) α-[[(4-Fluorophenyl)suUonyl]amino]-iV ' -hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (R-diastereomer), 4p) α-[[(4-Fluorophenyl)sulfonyl]amino]-iv ' -hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineaceta ide (αS-diastereomer), 4q) α-[2-[(3,4-Difiuorobenzoyl)amino]ethyl]-iV-hydroxy-3-(3-hydroxypropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4r) α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-hydroxyethyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4s) [R-(R*,S*)]-α-[2-[(3-Fluorobenzoyl)amino3ethyl]-N-hydroxy-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4t) S-(β*Jϊ*)]-N 3 -hydroxy-N 1 -methyl-α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 4u) [S-(β* r R*)]-N 1 -cyclopropyl-N 3 -hydroxy-α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide., 4v) [S-(i?*J2*)]-N 3 -hydroxy-α 1 -(l-methylethyl)-3-(2-methylpropyl)-2-oxo- N -phenyl- 1 ,3-pyrroUdinediacetamide, 4w) [S-(β*J?*)]-N 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrrolidinediacetamide, 4x) [S-(R* * )]-N 3 -hydroxy-α *-( l-methylethyl)-3-(2-methylpropyl)-2-oxo- N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 4y) [S-(-e*J^*)]-α 1 -tert-butyl-N 1 -cyclopropyl-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 4z) [S-(Λ*J2*)]-α 1 -tert-butyl-Λ^-hydroxy-3-(2-methylpropyl)-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 5a) [S-(JFe*J2*)]-α 1 -te^-butyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 5b) [S-(Λ* ff*)]-α 1 -terf-butyl-iV 3 -hydroxy-3-(2-methylpropyl)-2-oxo-iV 1 -(4- pyridinyl)-l,3-pyrroUdinediacetamide, 5c) [S-(R* J2*)]-α 1 -cyclohexyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-N 1 - phenyl- 1,3-pyrroUdinediacetamide, 5d) [S-( β * r R*)]-α 1 -cyclohexyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -(4- pyridinyl)- 1,3-pyrroUdinediacetamide, 5e) [S-(i?* R*)]-3-(cyclopentylmethyl)-N 3 -hydroxy-iV 1 -methyl-α 1 -( 1- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 5f) [-?-(β* τ β*)]-3-(cyclopentylmethyl)-iV 1 -cyclopropyl-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroHdinediacetamide, 5g) [S-(R* J?*)]-3-(cyclopentylmethyl)-iV 3 -hydiOxy-α 1 -( l-methylethyl)-2-oxo- N -phenyl- 1,3-pyrroUdinediacetamide, 5h) [S-(-R*Ji*)]-3-(cyclopentylmethyl)-N 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 5i) [S-(Λ*J?*)]-3-(cyclopentylmethyl)-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo- N -(4-pyridinyl)-l,3-pyrrohdinediacetamide, 5j) [S-( β *J2*)]-α 1 -tert-butyl-3-(cyclopentylmethyl)-N 3 -hydroxy-iV 1 -methyl- 2-oxo- 1,3-pyrroUdinediacetanιide, 5k) [S-(β*^*)]-α 1 -tert-butyl-3-((^clopentylmethyl)-N 1 -cyclopropyl-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 51) [S-(R* J?* )]-α 1 -tert-butyl-3-(cyclopentylmethyl)-N 3 -hydroxy-2-oxo-iv '1 - phenyl- 1,3-pyrroUdinediacetamide, 5m) [S-(i?* β *)]-α 1 -tert-butyl-3-(cyclopentymιethyl)-N 1 -(4-fluorophenyl)-iV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5n) [5-(.f?*Jϊ*)]-α 1 -terf-butyl-3-(cyclopentylmethyl)-iV 3 -hydroxy-2-oxo--V 1 -(4- pyridinyl)- 1, 3-pyrrolidinediacetamide, 5o ) [S-(B*J?*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-JV 3 -hydroxy-N 1 -methyl- 2-oxo-l, 3-pyrroUdinediacetamide, 5p) [S-(R* r R* )]-α 1 -cyclohexyl-3-(cyclopentylmethyl)- l -cyclopropyl-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5q) [S-(Λ*-ff*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl ) -N 3 -hydroxy-2-oxo-N 1 - phenyl- 1,3-pyrroUdinediacetamide, 5r) [S-(i2* r R*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-N 1 -(4-fluorophenyl)-JV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5s) [S-(-R* r β*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-N 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)-l,3-pyrroUdinediacetamide, 5t) [S-(Λ*J?*)]-iV 3 -hydroxy-N '1 -methyl-α 1 -(l-methylethyl)-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 5u) [S-(Λ*J?*)]-N 1 -cyclopropyl-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 5v) [S-(ie*J2*)]-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-N 1 -phenyl-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 5w) [S-(B*Je*)]-iV 1 -(4-fluorophenyl)-N 3 -hydroxy-a 1 -(l-methylethyl)-2-oxo-3- (3-phenylpropyl)-l,3-pyrroUdinediacetamide, 5x) [S-(β* J2*)]-iV 3 -hydroxy-a 1 -( l-methylethyl)-2-oxo-3-(3-phenylpropyl)- N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 5y) [S-(B* r R*)]-α 1 -ieτ -butyl-iV 3 -hydroxy-N 1 -methyl-2-oxo-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetamide, 5z) [S-(i2* R*)]-α 1 -tert-butyl-iV 1 -cyclopropyl-iV 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6a) [S-(Λ*J2*)]-α 1 -tert-butyl-iV 3 -hydroxy-2-oxo-N 1 -phenyl-3-(3- phenylpropyl)- 1 ,3-pyτroUdinediacetamide, 6b) [S-(i?*J2*)]-α 1 -tert-butyl-N 1 -(4-fluorophenyl)- 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6c) [S-(i?* fi*)]-α 1 -tert-butyl-N 3 -hydroxy-2-oxo-3-(3-phenylpropyl)-iV 1 -(4- pyridinyl)- 1,3-pyrroUdinediacetamid, 6d) [S-(_R*-R*)]-α 1 -cyclohexyl-iv '3 -hydroxy-iV 1 -methyl-2-oxo-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetamide, 6e) [S-(B* β*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-iV 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyττoUdinediacetamide, 6f) [S-(H* r R*)]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo-iV 1 -phenyl-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6g) [S-(β*J2*)]-α 1 -cyclohexyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrrolidinediacetamide, 6h) [S-(i?* r R*)]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo-3-(3-phenylpropyl)-iV 1 -(4- pyridinyl)- 1,3-pyrroUdinediacetamide, 6i) [S-(β* R*)]-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-N 1 -methyl-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6j ) [S-(R* r R*)]-N 1 -cyclopropyl-3-[3-(4-fluorophenyl)propyl]-iV 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6k) [S-(i?*J?*)]-3-t3-(4-fluorophenyl)propyl]-N 3 -hydroxy-α 1 -(l-methylethyl)- 2-oxo-N -phenyl- 1,3-pyrroUdinediacetamide, 61) tS-(i2*J2*)3-N 1 -(4-fluorophenyl)-3-[3-(4-fluorophenyl)propyl]-iV 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6m) [S-(fi* r β *)]-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-α 1 -(l-methylethyl)- 2-oxo-iV -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, 6n) [5-(i2*Je*)]-α 1 -tert-butyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-iV 1 - methyl-2-oxo- 1,3-pyrroUdinediacetamide, 6o) [S-(i2* r R*)]-α 1 -tert-butyl-N 1 -cyclopropyl-3-[3-(4-fluorophenyl)propyl]- Λ^-hydroxy--2-oxo-l,3-pyrroUdinediacetamide, 6p) [S-(iJ*-R*)]-α 1 -tert-butyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-2-oxo- N -phenyl-l,3-pyrroUdinediacetamide, 6q) [S-(Λ*-β*)]-α 1 -tert-butyl-V 1 -(4-fluorophenyl)-3-[3-(4-fluorophenyl)- propyl]- J V 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 6r) [S-( β *J?*)]-α 1 -tert-butyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-2-oxo- N -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, 6s) [S-(Λ* r R*)]-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-N 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 6t) [S-(R* J2* )]-α 1 -cyclohexyl-iv '1 -cyclopropyl-3-[3-(4-fluorophenyl)propyl]- Ar-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 6u) [5-( β *-R*)]-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyl]-iV 3 -hydroxy-2- oxo-N -phenyl- 1,3-pyrroUdinediacetamide, 6v) r5-(β*J2*)]-α 1 -cyclohexyl-N 1 -(4-fluorophenyl)-3-[3-(4- fluorophenyl)propyl]-_V -hydroxy-2-oxo- 1,3-pyrroUdinediacetamide, 6w) [5-(ie* f ff*)]-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-2- oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 6x) [S-(i2*J?*)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy-N 1 -methyl-α 1 -(l- methyleth3'l)-2-oxo-l,3-pyrroUdinediacetamide, 6y) [S-(i?* r R*)]-3-[3-(biphen-4-yl)propyl]-iV :l -cyclopropyl-iV 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6z) [S-(fi* r R*)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide, 7a) tS-(J?*J?*)]-3-[3-(biphen-4-yl)propyl]-N 1 -(4-fluorophenyl)-iV 3 -hydroxy- α 1 ^ l-methylethyl)-2-oxo- 1,3-pyrroUdinediacetamide, 7b) tS-(i?*J?*)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 7c) [S-(i2* R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -ϊert-butyl-N 3 -hydroxy-iV 1 - methyl-2-oxo- 1 ,3-pyrroHdinediacetamide, 7d) [S-(β*J2*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-N 1 -cyclopropyl-N 3 - hydroxy-2-oxo-l,3-pvrroUdinediacetaπύde, 7e) [S-(i?*J2*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-iV 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 7f) [S-(J?* R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-N 1 -(4-fluorophenyl)- N^-hy droxy-2 -oxo- 1 ,3-pyrroUdinediacetamide , 7g) [S-(fl* R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -ϊert-butyl-N 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)- 1,3-pyrroUdinediacetamide, 7h) [S-(Λ*J2*)]-3-[3-(biphen-4-yl)propyl]-α 1 -cyclohexyl-iV 3 -hydroxy-N 1 - methyl-2-oxo- 1,3-pyrroUdinediacetamide, 7i) [S-(i2*J?*)3-3-[3-(biphen-4-yl)propyl]-a 1 -cyclohexyl-A/ '1 -cyclopropyl-iV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7j) [S-(i?* f R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo- iV -phenyl- 1 ,3-pyrτoUdinediacetamide , 7k) [S-(β*J?*)]-3-[3-(biphen-4-yl)propyl]-α 1 -cyclohexyl-Λ rl -(4-fluorophenyl)- N -hydroxy-2-oxo- 1,3-pyrroUdinediacetamide, 71) [S-(R* r R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo- V -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, 7m) [S-(β* r R*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy-iV 1 -methyl-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 7n) [S-(R* J?* )]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 -cyclopropyl-N 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pvrroUdinediacetamide, 7o) [S-(β* r R*)]-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide, 7p) [S-(i?*-R*)]-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 1 -(4-fluorophenyl)-iV 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pvrroUdinediacetamide, 7q) [S-(β*-R*)]-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-N 1 -(4-pyridmyl)-l,3-pyrroUdinediacetamide, 7r) [S-(Λ*J?*)]-α 1 -tert-butyl-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 3 -hydroxy- N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide, 7s) [S-(Λ*J?*)]-α 1 -tert-butyl-iV 1 -cyclopropyl-3-[3-(4 , -fluorobiphen-4- yl)propyl]-N 3 -hydroxy-2-oxo-l,3-pvrroUdinediacetamide, 7t) [S-(i?*J?*)]-α 1 -tert-butyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo--V 1 -phenyl-l,3-pyrroUdinediacetamide, 7u) [S-(i?* r β*)]-α 1 -terr-butyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 -(4- fluorophenyl)-Λ^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7v) [S-(i?* R*)]-α 1 -tβrt-butyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-iV 3 -hydroxy- 2-oxo-N -(4-p yridinyl)- 1 , 3-pyrroUdinediacetamide, 7w) [S-(Λ* fl*)]-α 1 -cyclohexyl-3-[3-(4'-fluorobiphen-4-yl)propyl]-iV 3 -hydroxy- N -methyl-2-oxo- 1,3-pyrroUdinediacetamide, 7x) [S-(ie*J?*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-3-[3-(4'-fluorobiphen-4- yl)propyl]-N -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7y) [S-(i?*J2*)]-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo-iV 1 -phenyl-l,3-pyrroUdinediacetamide, 7z) [5-(i?* r β*)]-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 -(4- fluorophenyl)-Λ^-hydroxy-2-oxo-l,3-pvrroUdinediacetamide, 8a) [S-(β*J2*)]-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo-iV -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 8b) Preparation of [S-(i2* r R*)]-3-heptyl-N 3 -hydroxy-N 1 -methyl-α 1 -( 1- methylethyl)-2-oxo-l,3-pyrτoUdinediacetamide, 8c) Preparation of [S-(R* Je*)]-7v rl -cyclopropyl-3-heptyl-N 3 -hydroxy-α *-( 1- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 8d) Preparation of [S-(β*J?*)]-3-heptyl-N 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-N -phenyl-l,3-pyrroUdinediacetamide, 8e) Preparation of [S-(β*Jϊ*)]-3-heptyl-N 1 -(4-fluorophenyl)-iV 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 8f) Preparation of [S-(-R*J?*)]-3-heptyl-iV 3 -hydroxy-a 1 -(l-methylethyl)-2- oxo-iV 1 -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, 8g) Preparation of [S-(i?* β*)]-α 1 -tert-butyl-3-heptyl-N 3 -hydroxy-N 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 8h) Preparation of [S-(β*J2*)]-α 1 -tert-butyl-N 1 -cyclopropyl-3-heptyl-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8i ) Preparation of [S-( β * r R*)]-α 1 -tert-butyl-3-heptyl-iV 3 -hydroxy-2-oxo-iv "1 - phenyl- 1 , 3-pyrrolidinediacetamide, 8j) Preparation of [S-( β *J?*)]-α 1 -tert-butyl-N 1 -(4-fluorophenyl)-3-heptyl- N 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8k) Preparation of [S-(Λ* r fl*)]-α 1 -tert-butyl-3-heptyl-N 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)-l,3-pyrroUdinediacetamide, 81) Preparation of [S-(i?* ff*)]-α 1 -cyclohexyl-3-heptyl-N 3 -hydroxy-N 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 8m) Preparation of [S-(i?*J?*)]-a 1 -cyclohexyl-iV 1 -cyclopropyl-3-heptyl-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8n) Preparation of [S-(J?*J2*)]-a 1 -cyclohexyl-3-heptyl-N 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 8o) Preparation of [S-(i?* r R*)]-α 1 -cyclohexyl-3-heptyl-N 1 -(4-fluorophenyl)- N 3 -hydroxy-2-oxo-l,3-pvrroUdinediacetamide, and 8p) Preparation of [S-(i2*J?*)]-α 1 -cyclohexyl-3-heptyl-N 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)- 1,3-pyrroUdinediacetamide. The compounds represented by the general formula I can be prepared by the methods of reaction in Schemes A-D. As shown in Scheme A-l, structure 2 is readily prepared from structure 1 (commerciaUy available) according to the procedures described in J. Am. Chem. Soc. Vol. 75, 3679 (1953). Alkylation of structure 2 requires an alkyl group (R χ ) attached to an appropriate leaving group. The alkylation occurs in the presence of a suitable base such as Uthium diisopropylamide (LDA) at a suitable temperature in the range -78 °C to 5 °C to provide structure 3. The ester side chain of structure 4 is introduced by alkylation of 3 with an alkyl (R' = C^g alkyl) bromoacetate in the presence of a suitable base such as LDA in a suitable solvent such as tetrahydrofuran (THF), at a suitable temperature in the range -78 °C to 0 °C. Hydrolysis of structure 4 by the procedures weU known to one of ordinary skiU in the art affords structure 5, which is then converted to the hydroxamate 6 by reaction of structure 5 with hydroxylamine hydrochloride and l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDO as an acid activating agent at a suitable temperature in the range -20 °C to 20 °C. The reaction occurs in the presence of a catalyst such as 1-hydroxybenzotriazole hydrate (HOBT) and an appropriate acid scavenger such as N-methylmorpholine in a suitable solvent such as DMF, CH 2 C1 2 or a mixture thereof . Alternatively, alkylation of structure 4 with a haUde compound I-R 2 (I is halogen, R<2 is defined as above) by procedures weU known to one of ordinary skill in the art affords structure 7. For example, alkylation of 4 with aUyl bromide introduces an aUyl group on the α-position of side chain using a suitable base such as LDA in a suitable solvent such as THF at a suitable temperature in the range -78 °C to 25 °C. The resultant allyl intermediate is then converted to the corresponding alcohol by ozonelysis and reduction NaBH 4 or by hydroboration with 9-BBN. In many cases the alcohols are converted to a phthaUmide via the Mitsunobu protocol. Alternatively, the alcohol can be converted to a leaving group (such as Ms, Ts) which is subsequently displaced with the desired nucleophile such as SR, NR2, OR, etc. The remaining synthetic steps which leads structure 7 to structure 9 is similar to that described above. A sUghtly different approach is employed to prepare 16 as shown in Scheme A-2, which incorporates a terminal amide R 4 (R 4 is as defined above, except R 4 is not hydrogen). Alkylation of commercially avaUable 10 affords lactam 11 according to the procedures described in Fisher, M. J. and Overman, L. E., J. Org. Chem., Vol. 55, pp 1447-1459 (1990). Lactam 11 is reacted with aUyl bromide to provide 12. The yields for this reaction are generaUy quite high. Alkylation of 12 with ethyl bromoacetate provides ester 13. Structure 13 is then converted to the corresponding amide 14, which foUowed by oxidation with ruthenium tetroxide in a solvent mixture such as carbontetrachloride, water, and acetonitrile at room temperature affords pyrroUdineacetic acid 15. The step which leads from structure 15 to structure 16 is similar to that described above in Scheme A-l. Scheme A-3 iUustrates another method for preparing the compounds of formula I. As shown in Scheme A-3, reaction of structure 10 with di-tert-butyl dicarbonante in the presence of DMAP provided protected lactam 17. Alkylation of 17 with alkyl or alkenyl haUdes in the presence of HMPA provides lactam 18. The ester side chain of structure 19 is introduced by alkylation of 18 with alkyl bromoacetate as described in Scheme A-l. Structure 19 can then be deprotected using magnesium methoxide in a suitable solvent according the procedure described in Tetrahedron Lett. Vol. 35, p 847 (1994) to provide structure 20. Alteratively, alkylation of 19 with a haUde compound I-P^ by procedures weU known to one of ordinary skill in the art affords structure 21. Deprotection of structure 21 affords structure 22. The R substituent can be introduced directly by N-alkylation of 20 or 22 with a desired haUde compound using a suitable base such as sodium hydride in a suitable solvent such as THF or DMF to provide structures 4 or 7, respectively. If desired, lactam 20 and 22 can be resolved using chiral HPLC or chemical methods to provide the corresponding enantiomers as illustrated in Examples 2 and 28. Each antipode can be converted to the appropriate chiral analogs 20a and 22a as shown in Scheme A-4. Lactam 20 and 22, either as the racemate or a single enantiomer, are used in the alkylation steps as described in Schemes A-3 and A-4. As shown in scheme A-4, the alkylation of lactam 20a or 22a with the trifiate 23 affords 24 and 28, respectively. For simpUcity, only a single antipode of 20a or 22a and trifiate 23 are presented. This chemistry can be carried out for both the racemate or a single enantiomer. Trifiate 23 can be prepared foUowing the procedure described in J. Org. Chem. Vol. 58, pp 2725-2737 (1993). A preferred approach to provide 24 involves deprotonation of 20a with a suitable base such as sodium hydride in a suitable solvent such as THF at a temperature in the range - 20°C to 15 °C, foUowed by the addition of trifiate 25. Warming to ambient temperature affords desired structure 24. If racemate 20 is utilized the diastereomers can be separated at this stage by siUca gel chromatography or HPLC. Hydrolysis of the methyl ester 24 with aqueous NaOH provide 25, which foUowing the formation of an amide by the procedure outlined in Scheme A-3, affords 26. The remaining synthetic steps which lead from structure 26 to structure 27 are siπύlar to that described in Scheme A-l. In a similar fashion, the compounds represented by structure 31 are prepared. Alternatively, an enantiospecific method can by employed to prepare a single antipode as shown in Scheme A-5. Alkylation of commerciaUy avaUable compound 32 requires an alkyl or aUyl (R-^) attached to a leaving group in the presence of a suitable base such as lithium diisopropylamide (LDA) provides structure 33 as a mixture of diastereoisomers at the C-3 position of the ring. The mixture is alkylated with allyl bromide to provide 34 in opticaUy pure form as shown in A-5. The trityl group is removed with TFA to provide 35, which is converted to lactol 36 following the protocol described in J. Chem. Soc. C.C. pp 1119-1122 (1989). The key cycUzation step is effected quite simply by reaction of the lactol 36 with an amine 37 in the presence of sodium cyanoborohydride foUowed by heating the crude uncycUzed intermediate at reflux in toluene to provide 38 as a single isomer. Amine 37 can be prepared through the conversion of a commercial available L-, or D-amino acid to the corresponding amine by procedures weU known to one of ordinary skiU in the art. FoUowing the chemistry outlined in Schemes A-2, the olefin is oxidized with ruthenium tetroxide to provide 39, which is coupled with 0-benzylhydroxylamine hydrochloride (CDI, THF) and then deprotected by hydrogenation with palladium on carbon to provide 41. A series of other ring system are synthesized as shown in Schemes B-E. Scheme B illustrates a method for preparing 2,5-dioxo pyrrolidines. Exhaustive ruthenium tetroxide oxydation of 4 in the presence of sodium periodate in the suitable solvent such as water/acetonitrile/carbontetrachloride at an ambient temperature provides 42. In a similar fashion as described in Scheme A-l, hydroxamate 43 is prepared. Two different synthetic routes are developed for the synthesis of the hydantoin analogs as shown in Schemes C-l and C-2. In Scheme C-l, N-alkylation of 1-methylhydantoin 44 with 2-bromoethylbenzene occurs in the presence of a suitable base such as sodium hydride, in a suitable solvent such as DMF, at the temperature in the range -20°C to 15 °C. FoUowing C-alkylation with a haUde compound in the presence of a suitable base such as LDA at the temperature in the range -78°C to 15 °C affords 46. Formation of the quaternary center through C- alkylation with an alkyl bromoacetate in the presence of a suitable base such as LDA at the temperature in the range -78°C to 15 °C affords 47. Conversion of 47 to the hydroxamate 48 is conducted following the previously outlined procedures. An alternative approach is developed for the synthesis of the unsubstituted (1-H) hydantoin analog of 48. Amino acid 49 can be prepared according to the procedures described in DeUaria, J. F., J. ORG. Chem. Vol. 53, p 5607 (1988). FoUowing the general procedure of Van der Veen, J.M. at el. J. C. S. Perkin II pp 653-658 (1979), amino acid 49 is reacted with an appropriate substituted isocyanate foUowed by cycUzation under acidic conditions to provide hydantoin 50. The remaining synthetic steps which lead to structure 52 are similar to that described previously. Scheme D iUustrates an approach into a pyrazoUdinone ring system. Protection of pyrrazoUdinone 53 by the procedures described in Perri, S. T. at el., J. Org. Chem., Vol. 55, pp 6037-6047 (1990) provides 54. FoUowing N-alkylation and C-alkylations as outlined previously, lead to structure 57. An atmosphere of hydrogen is placed over a mixture of 57 and Pearlman's catalyst in a suitable solvent such as MeOH at ambient temperature to afford the desired compound 58. The pharmaceutical compositions of this invention may be prepared by combining the compounds of formula I of this invention with a soUd or liquid pharmaceutically acceptable carrier, and optionaUy, with pharmaceuticaUy acceptable adjuvants and excipients employing standard and conventional techniques. SoUd form compositions include powders, tablets, dispersible granules, capsules and suppositories. A solid carrier can be at least one substance which may also function as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, tablet disintegrating agent, and encapsulating agent. Inert soUd carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, ceUulosic materials, low melting wax, cocoa butter, and the like. Liquid form compositions include solutions, suspensions and emulsions. For example, there may be provided solutions of the compounds of this invention dissolved in water, water-propylene glycol, and water-polyethylene glycol systems, optionally containing conventional coloring agents, flavoring agents, stabilizers and thickening agents. The pharmaceutical composition is provided by employing conventional techniques. Preferably the composition is in unit dosage form containing an effective amount of the active component, that is, the compounds of formula I according to this invention. The quantity of active component, that is the compounds of formula I according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular appUcation method, the potency of the particular compound and the desired concentration. GeneraUy, the quantity of active component will range between 0.5% to 90% by weight of the composition. In therapeutic use for treating a patient, suffering from or susceptible to a diseases involving connective tissue degradation, or inhibiting various enzymes from the matrix metaUoproteinase family, including coUagenase, stromelysin, and gelatinase, the compounds or pharmaceutical compositions thereof wiU be administered oraUy, parenteraUy and/or topicaUy at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level of active component in the patient undergoing treatment which wiU be effective to inhibit such enzymes. GeneraUy, an effective amount of the active compound will be in the range of about 0.1 to about 100 mg/kg. It is to be understood that the dosages may vary depending upon the requirements of the patient, the severity of connective tissue degradation being treated, and the particular compounds being used. Also, it is to be understood that the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or the initial dosage may be smaUer than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, e.g., two to four times per day. The compounds of the present invention inhibit various enzymes from the matrix metaUoproteinase family, including coUagenase, stromelysin, and gelatinase, and hence are useful for the treatment of matrix metaUo endoproteinase diseases such as osteoarthritis, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, and other diseases related to connective tissue degradation. Such diseases and conditions are weU known and readUy diagnosed by physician of ordinary skiU. These compounds may also inhibit the release of cytokines including tumor necrosis factor (TNFa) and hence may also be useful in inflammation, fever, acute infections and shock. In general, the preferred form of administration is oraUy. Pharmaceutical compositions for parenteral administration will generaUy contain a pharmaceuticaUy acceptable amount of the compounds according to formula I as a soluble salt (acid addition salt or base salt) dissolved in a pharmaceuticaUy acceptable Uquid carrier such as, for example, water-for-injection and a suitably buffered isotonic solution having a pH of about 3.5-6. Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N-methylglucamine, L(+)-lysine and L(+)-arginine, to name a few. The compounds according to formula I generaUy will be dissolved in the carrier in an amount sufficient to provide a pharmaceuticaUy acceptable injectable concentration in the range of about 1 mg/ml to about 400 mg/ml. The resulting Uquid pharmaceutical composition will be administered so as to obtain the above-mentioned inhibitory effective amount of dosage. The compounds of formula I according to this invention are advantageously administered orally in soUd and liquid dosage forms. Inhibitory activity is evaluated in one or more of the MMP enzymes (stromelysin, gelatinase, and coUagenase) in vitro using a particle concentration fluorescence techniques. An inhibitor binds to MMP enzymes prevents the degradation of a substrate of stromelysin, gelatinase, or coUagenase. The substrate is attached with a fluorescein and a biotin. The intact substrate then binds to an avidin-coated particle via the biotin moiety. Once the particle is washed and dried, a fluorescent signal is generated since the fluorescent group is attached to the particle. Without an inhibitor present, the substrate is degraded by MMP enzymes and the fluorescein group is removed, therefore, no fluorescent signal can be detected. Testing compounds are dissolved in DMSO to the desired concentration, then the solutions are diluted to 1:5 with MMP buffer (50 roM Tris-HCl, pH 7.5; 150 mM NaCl; 0.02% NaN 3 ). Serial two-fold dUutions of each compound are prepared. A concentrated, activated enzyme solution is transferred into each plate of the testing compounds, and the mixture is incubated at room temperature for 15 minutes. Thawed MMP substrate is then added into aU plates, and the plates are incubate in the dark for 1-3 hours at room temperature. At this point, the substrate mixture is reacted with 0.1% avidin-coated polystyrene particles. After 15 minutes, the inhibitory activities are evaluated by Ki assay. Inhibitory data for the compounds of this invention are shown in TABLE 1. Compounds with lower Ki value are expected to be more effective as MMP inhibitors. It is expected that a compound with a Ki less than 15 μM against any one of the MMP's will display therapeutic effects in connective tissue disorders. TABLE 1 MMP Inhibition Constants (K/, μM) for Hydroxamic Acid Derivatives In order to more fully illustrate the nature of the invention and the manner of practicing the same, the following experimental examples are presented, but they should not be taken as limiting. Example 1 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrroUdineacetamide . Step 1. Preparation of l-(2-Phenylethyl)-2-pyrroUdinone. FoUowing the procedure of Boekelheide and Godfrey (J. Am. Chem. Soc. 1953, 75, 3679), γ-butyrolactone (50.0 mL, 650 mmol) and phenethylamine (85.0 mL, 677 mmol) are heated in a sealed reaction vessel from room temperature to 200 °C over 2.5 hours, at 280-300 °C for 2 hours, and is allowed to cool to room temperature. The reaction mixture is distilled (1.5 mm, 130-144 °C) to yield 107 g of the title compound which solidified upon standing (mp 50.5-52.5 C C). IR (mineral oil) 3334, 3079, 3022, 1671, 1634, 1498, 1493, 1433, 1425, 1328, 1280, 1248, 1156, 759, 707 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.10-7.35, 3.53, 3.25, 2.84, 2.35, 1.8-2.0; MS (El) mlz 189, 104, 98, 70. Step 2. Preparation of 3-(2-Methylpropyl)-l-(2-phenylethyl)-2-pyrrolidinone. A solution of l-(2-phenylethyl)-2-pyrroUdinone (500 mg, 2.64 mmol) and THF (6 mL) is cooled to -78 °C. Some precipitation occurred and 2 mL of THF is added. A solution of Uthiu diisopropylamide (LDA, 1.4 mL, 2.8 mmol, 2.0 M in heptane/THF/ethylbenzene) is added and the mixture stirred at -78° C for 40 minutes, giving a dark brown solution. To this solution is added l-iodo-2- methylpropane (0.37 mL, 3.2 mmol). The solution is aUowed to warm from -78 °C to 5 °C over 2.5 hours. After quenching with saturated aqueous ammonium chloride, aqueous workup (EtOAc, MgS0 4 ) and purification by column chromatography (20% EtOAc/hexane) to give 642 mg (99%) of the title compound as a white soUd (mp 69- 71 °C). IR (mineral oU) 3032, 3002, 1665, 1632, 1499, 1441, 1425, 1303, 1271, 1168, 772, 745, 704, 619 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.15-7.40, 3.40-3.65, 3.10-3.20, 2.84, 2.35-2.45, 2.05-2.2, 1.45-1.80, 1.10-1.25, 0.93, 0.89; MS (El) mlz 245, 189, 154, 126, 98, 54. Step 3. Preparation of tert-Butyl 3-(2-Methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate. LDA (2.0 M, 11.5 mL, 23.0 mmol) is added to a solution of 3-(2-methylpropyl)- l-(2-phenylethyl)-2-pyrroUdinone (4.70 g, 19.2 mmol) and THF (80 mL) at -78 °C. The solution is stirred at -78 °C for 45 minutes, and tert-butyl bromoacetate (3.4 mL, 23 mmol) is added. The solution is aUowed to warm to 0 °C over 2 hours and is allowed to stir overnight at room temperature. After quenching with saturated aqueous ammonium chloride, aqueous workup (EtOAc, MgS0 4 ) and purification by column chromatography (10% EtOAc/5% CH^ ^hexane) to give 4.67 g (68%) of the title compound as a colorless oil. An analytical sample is crystallized from hexane (mp 50 °C). IR (liq.) 2957, 2930, 2870, 1728, 1688, 1497, 1455, 1444, 1429, 1367, 1347, 1278, 1258, 1156, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.6-3.75, 3.35-3.5, 3.15-3.25, 2.85, 2.43, 2.05-2.2, 1.9-2.0, 1.55-1.7, 1.35-1.5, 1.42, 0.88, 0.86; MS (El) mlz 359, 303, 286, 268, 247, 212, 184, 166, 156, 138, 105. Step 4. Preparation of 3-(2-Methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetic Acid. A solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (659 mg, 1.83 mmol), trifluoroacetic acid (6.5 mL) and CH 2 C1 2 (6.5 mL) is stirred at room temperature for 1 hour. The solution is concentrated from CH 2 C1 2 (3 x 50 mL), dissolved in 1 N NaOH (10 mL), and the basic layer is extracted with Et2θ (2 x 25 mL). The pH of the basic layer is adjusted to pH 1 with 6 N HC1. The acidic layer is extracted with CH 2 C1 2 (2 x 25 mL), the combined CH^J^ layers dried (MgS0 4 ), filtered and concentrated to give 511 mg (92%) of the title compound as a colorless oil. IR (mineral oil) 3065, 3029, 1738, 1647, 1497, 1440, 1304, 1213, 1183, 1171, 1152, 1112, 756, 733, 701 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.10-7.35, 3.50-3.70, 3.15-3.35, 2.89, 2.55, 2.05- 2.15, 1.60-1.85, 1.57, 1.36, 0.91, 0.87; MS (El) mlz 303, 247, 213, 212, 184, 166, 156, 138, 105, 104. Step 5. Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrroUdineacetamide. SoUd l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 451 mg, 2.35 mmol) is added to a solution of 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrrolidineacetic acid (595 mg, 1.96 mmol), 1-hydroxybenzotriazole hydrate (HOBT, 281 mg, 2.08 mmol) and 4-methylmorpholine (0.26 mL, 2.4 mmol) in CH 2 C1 2 (19 mL) and DMF (4 mL) at 0 °C. The solution is stirred at 0 °C for 1 hour, and then a near solution of hydroxylamine hydrochloride (204 mg, 2.94 mmol) and 4- methylmorpholine (0.32 mL, 2.9 mmol) in DMF (2.7 mL) is added. After stirring at room temperature overnight, the mixture is concentrated under high vacuum, and purified by column chromatography (3% MeOH/CH 2 Cl 2 ). Crystallization from Et 2 O/hexane provided 193 mg (31%) of the title compound as a white solid (mp 123- 124 °C). IR (mineral oU) 3205, 3071, 3026, 1664, 1638, 1496, 1353, 1316, 1296, 1283, 1271, 1078, 982, 751, 705 cm ; 1H NMR (300 MHz, CDC1 3 ) δ 7.15-7.35, 3.55, 3.10-3.30, 2.84, 2.39, 1.85-2.20, 1.55-1.75, 1.50, 1.32, 0.88, 0.85; MS (El) mlz 318, 227, 211, 193, 182, 166, 154, 138, 110, 105. EXAMPLE 2 Preparation of (3S)-N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. Resolution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate. A solution of 50 mg/mL of racemic tert-butyl 3-(2-methylpropyl)- 2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 1, step 3) is made in the mobUe phase that consisted of 10% isopropanol in hexane (V/V). AUquots of 3.5 mL (175 mg) are injected onto a 2.1x25 cm Chiralpak AD column (Chiral technologies, Inc.). The column is eluted at 10 mL min and monitored at 220 nm. The two enantiomers are collected using a peak recognition program and fractions are pooled appropriately. Each enantiomer is obtained at >99% ee. Enantiomeric excess is determined on a 0.46x25 cm Chiralpak AD column (Chiral Technologies, Inc.), developed with the same solvent at 0.5 mL/min and the monitor set at 220 nm. The retention times here are 12.2 and 23.0 minutes (α = 2.61). Following the general procedure outlined in EXAMPLE 1 (steps 4-5), and making non-critical variations but starting with (S)-tert-butyl 3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrrolidineacetate (the faster eluting enantiomer described above), the title compound is obtained. 1H NMR (300 MHz, CDClg) δ 7.10-7.35, 3.40-3.70, 3.10-3.30, 2.75-2.95, 2.38, 1.15-2.20, 0.75-1.00. EXAMPLE 3 Preparation of N-Hydroxy-α-methyl-3-(2-methylpropyI)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide . Step 1. Preparation of tert-Butyl α-Methyl-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate. LDA (1.5 mL, 3.0 mmol, 2.0 M in heptane/THF/ethylbenzene) is added to a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (967 mg, 2.69 mmol) and THF (11.0 mL) at -78 °C. The solution is stirred at -78 °C for 30 minutes and then iodomethane (0.19 mL, 3.1 mmol) is added. The solution is stirred at -78 °C for 2 hours and then aUowed to slowly warm to room temperature overnight. Aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (1:1 hexane:EtOAc) gives 791 mg (79%) of the title compound as an oU. IR (Uq.) 2975, 2956, 2931, 2869, 1724, 1686, 1497, 1455, 1429, 1367, 1279, 1257, 1153, 1114, 700, cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 7.15-7.35, 3.60-3.75, 3.30-3.45, 3.25, 2.82, 2.65, 2.25-2.40, 1.50-1.80, 1.35-1.50, 1.40, 1.12, 0.86, 0.84; MS (El) mlz 373, 317, 300, 282, 261, 227, 226, 152, 105, 104, 57. Step 2. Preparation of α-Methyl-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetic Acid. TFA (10.0 L) is added to a solution of tert-butyl α-methyl-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (780 mg, 2.09 mmol) and CH 2 C1 2 (10 mL) at 0 °C. The solution is stirred for 2.5 hours at 0 °C and 1.5 hours at room temperature. After concentration, the residue is partitioned between EtOAc and water. The organic layer is extracted several times with 10% NaOH, the combined basic layers acidified (4 N HC1), and the acidic layers extracted several times with CH^lg. The CH 2 C-2 layers are dried (MgS0 4 ), filtered, and concentrated to provide 79 mg (12%) of the title compound as a white soUd (mp 94- 95 °C). IR (mineral oil) 2400, 1731, 1616, 1505, 1497, 1488, 1443, 1354, 1326, 1289, 1266, 745, 736, 702, 607, cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 7.15-7.35, 3.65-3.85, 3.45-3.60, 3.20-3.40, 2.90, 2.59, 1.50-2.10, 1.06, 0.89, 0.85; MS (El) mlz 317, 261, 227, 226, 216, 180, 152, 105, 104, 55. Step 3. Preparation of N-Benzyloxy-α-methyl-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide . CDI (39.7 mg, 0.245 mmol) is added to a solution of α-methyl-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid (74.0 mg, 0.233 mmol) and CH 2 C1 2 (2.0 mL). The solution is stirred for 1 hour at room temperature. To this is added 0-benzyU ydroxylamine-HCl (63.2 mg, 0.396 mmol) and N- methylmorpholine (44 μL, 0.40 mmol). The resultant solution is stirred for 16 hours at room temperature. Aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by flash chromatography (2:1 EtOA hexane) gives 88.1 mg (89%) of the title compound as an oU. IR (liq.) 3230, 3063, 3029, 2956, 2936, 2869, 1664, 1497, 1454, 1367, 1310, 1282, 1029, 748, 699 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 10.16, 7.10-7.45, 4.87, 3.35-3.60), 3.10-3.30, 2.81, 2.42, 2.10-2.30, 1.75-1.90, 1.35-1.70, 1.05, 0.85, 0.79; MS (El) mlz 422, 300, 225, 196, 152, 105, 104, 91, 77, 69, 55. Step 4. Preparation of N-Hydroxy-α-methyl-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. An atmosphere of hydrogen is placed over a mixture of N-benzyloxy-α- methyl-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (80.0 mg, 0.189 mmol), MeOH (4.5 mL) and Pearlman's catalyst (15 mg). The mixture is stirred at room temperature for 4 hours. The mixture is filtered, the solids rinsed with MeOH ( X 5 mL), and the filtrate concentrated to give 55.9 mg of an oU. CrystaUization from hexane provided 46.9 mg (75%) of the title compound as a white solid (mp 107-108 °C). IR (mineral oU) 3227, 3044, 3026, 1658, 1641, 1498, 1436, 1294, 1262, 1031, 774, 735, 713, 695, 611 cm "1 ; MS (FAB) mlz 333, 332, 301, 300, 272, 105, 69, 55, 41. EXAMPLE 4 Preparation of α-[2-(l,3-Dinydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. Step 1. Preparation of tert-Butyl 3-(2-Methylpropyl)-2-oxo-l-(2-phenylethyl)-α- (propen-2-yl)-3-pyrrolidineacetate. LDA (2.0 M, 7.7 mL, 16 mmol) is added to a solution of tert-butyl 3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 1, step 3; 4.62 g, 12.9 mmol) and THF (45 mL) at -78 °C. The solution is stirred at -78 °C for 45 minutes and aUyl bromide (1.3 mL, 16 mmol) is added. The solution is aUowed to warm to 0 °C over 2 hours, and is aUowed to stir overnight at room temperature. After quenching with saturated aqueous ammonium chloride, aqueous workup (EtOAc, MgSO 4 ) and purification by column chromatography (2:1:17 v/v EtOAc :CH 2 Cl 2 :hexane) gives 4.43 g (86%) of the title compound as yeUow oU which soUdified upon standing (mp 54.5-56 °C). IR (mineral oU) 1712, 1686, 1641, 1497, 1432, 1298, 1281, 1270, 1250, 1237, 1205, 1155, 912, 752, 702, cm "1 ; X H NMR (300 MHz, CDClg) δ 7.15-7.35, 5.65-5.8, 4.95-5.1, 3.55-3.7, 3.3-3.45, 3.15-3.25, 2.82, 2.53, 2.2-2.5, 1.7-1.85, 1.5-1.65, 1.35-1.45, 1.40, 0.87, 0.83; MS (El) mlz 399,343, 326, 308, 253, 252, 234, 202, 105, 57. Step 2. Preparation of tert-Butyl α-(2-Hydroxyethyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate. Ozone is bubbled through a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-α-(propen-2-yl)-3-pyrroϋdineacetate (555 mg, 1.39 mmol) and EtOH (12 mL) at -78 °C for 5 minutes. Nitrogen is then bubbled through the solution for 5 minutes. Sodium borohydride (79 mg, 2.1 mmol) is added and the mixture is aUowed to warm slowly and to stir at room temperature overnight. The mixture is concentrated to near dryness, and aqueous workup (EtOAc, MgS0 4 ) to give 511 mg (91%) of the title compound as a colorless oU. IR (liq.) 2957, 2931, 2870, 1720, 1672, 1671, 1497, 1455, 1392, 1367, 1282, 1257, 1152, 1055, 701 cm '1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.15-7.35, 3.55-3.75, 3.35-3.45, 3.15-3.25, 2.82, 2.61, 2.3-2.45, 1.85-2.0, 1.65-1.8, 1.35-1.60, 1.43, 0.87, 0.83; MS (El) mlz 403, 347, 330, 291, 270, 256, 238, 227, 202, 181, 105, 104. Step 3. Preparation of tert-Butyl α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate. Diethyl azodicarboxylate (182 uL, 1.16 mmol) is added to a mixture of tert- butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (468 mg, 1.16 mmol), triphenylphosphine (304 mg, 1.16 mmol), phthalimide (171 mg, 1.16 mmol) and THF (10 mL) at room temperature. The mixture is aUowed to stir overnight and is concentrated. Purification by column chromatography (2 columns, 5% acetone/CH 2 Cl 2 and 10% EtOAc hexane) provided 327 mg (51%) of the title compound as a colorless oil. IR diq.) 2956, 2932, 1773, 1716, 1685, 1467, 1454, 1438, 1397, 1368, 1299, 1255, 1152, 720, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.8-7.9, 7.65-7.75, 7.15-7.35, 3.55-3.8, 3.3-3.4, 3.15-3.25, 2.80, 2.51, 2.3-2.4, 2.0-2.15, 1.8-1.95, 1.6-1.8, 1.35-1.6, 1.46, 0.85, 0.82; MS (El) mlz 532, 476, 459, 441, 420, 385, 339, 311, 245, 202, 160, 105. Step 4. Preparation of α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrrolidineacetic Acid. Trifluoroacetic acid (2.0 mL) is added to a solution of tert-butyl α-[2-(l,3- dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrroUdineacetate (282 mg, 0.507 mmol) in CH 2 Cl 2 (4.0 mL) at 0 °C. The solution is stirred for 1 hour at 0 °C. A second portion of trifluoroacetic acid (2.0 mL) is added, and the solution is stirred for 30 minutes at 0 °C and for 30 minutes at room temperature. Concentration and aqueous workup (CH 2 C1 2 , MgS0 4 ) to give 217 mg (90%) of the title compound as a colorless oil. (mineral oil) 1711, 1606, 1509, 1498, 1485, 1445, 1403, 1359, 1295, 1262, 1244, 1111, 704 cm "1 ; NMR (300 MHz, CDClg) δ 7.85-7.9, 7.7-7.8, 7.15, 6.9-7.0, 3.7-3.9, 3.55- 3.65, 3.35-3.5, 3.25-3.35, 2.75-2.95, 2.49, 2.0-2.1, 1.80-1.95, 1.65-1.75, 1.5-1.65, 1.2- 1.45, 0.91, 0.84; MS (El) mlz 476, 420, 385, 339, 311, 272, 258, 202, 160, 105. Step 5. Preparation of N-Benzyloxy-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. CDI (82 g, 0.51 mmol) is added to a solution of α-[2-(l,3-dihydro-l,3-dioxo- 2H-isoindol-2-yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid (202 mg, 0.424 mmol) and CHgCl^ (3.2 mL) at room temperature, and the solution is stirred for 1 hour at room temperature. O-Benzy ydroxylamine hydrochloride (98 mg, 0.614 mmol) and 4-methylmorpholine (84 uL, 0.76 mmol) are added in succession, and the solution is aUowed to stir overnight at room temperature. Aqueous workup (CH^CL^, MgS0 4 ) and purification by column chromatography (2% acetone/CH 2 C-2) gives 120 mg (49%) of the title compound as a colorless oil. IR (mineral oU) 1773, 1715, 1683, 1663, 1662, 1497, 1398, 1340, 1301, 1270, 1038, 1030, 748, 699 cm "1 ; NMR (300 MHz, CDClg) δ 7.8-7.9, 7.7-7.8, 7.05-7.55, 4.93, 3.55-3.8, 3.48, 3.1-3.2, 2.77, 2.15-2.3, 1.7-1.9, 1.35-1.65, 0.80, 0.73; MS (FAB) mlz 582, 459, 431, 160, 105, 91. Step 6. Preparation of α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdine- acetamide. A mixture of N-benzyloxy-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (58 mg, 0.10 mmol) and 5% Pd/C (20 mg) is stirred for 1.5 hours at room temperature under an atmosphere of hydrogen. Palladium hydroxide on carbon (10 mg) is added and the mixture is stirred under hydrogen at room temperature for 6 hours. The mixture is filtered and the filtrate is concentrated. Purification by column chromatography (5% MeOH/EtOAc) gives 39 mg of an oil which is crystallized from EtOAc/hexane to give 29 mg (59%) of the title compound as a white soUd (mp 158-159 °C). IR (mineral oil) 3212, 3101, 3087, 3005, 1773, 1711, 1659, 1495, 1444, 1401, 1310, 1292, 1040, 706 cm " NMR (300 MHz, CDClg) δ 10.19, 7.8-7.9, 7.7-7.8, 7.05-7.35, 6.9-7.0, 3.3- 3.8, 3.19, 2.79, 2.39, 2.1-2.3, 1.75-2.0, 1.35-1.7, 0.83, 0.76; MS (El) mlz 491, 459, 435, 419, 400, 375, 355, 327, 262, 261, 245, 202, 160, 105. EXAMPLE 5 Preparation of (3S)-α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]- N-hydroxy-3-(2-methylpropyl)-2-oxo- 1-( 2-phenylethyl)-3- pyrroUdineacetamide. FoUowing the general procedure outlined in EXAMPLE 4, and making non- critical variations but starting with (Shtert -butyl 3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate (EXAMPLE 2, faster eluting enantiomer), the title compound is obtained (mp 102-105 °C). IR (mineral oil) 3546, 3172, 3087, 3064, 3024, 1770, 1717, 1665, 1497, 1434, 1407, 1303, 746, 725, 703 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.80-7.90, 7.65-7.80, 7.05-7.35, 6.80, 3.25-3.80, 3.10-3.25, 2.79, 2.35-2.45, 2.10-2.30, 1.75-2.00, 1.30-1.75, 0.83, 0.76; MS (El) mlz 491, 459, 435, 431, 327, 262, 261, 244, 160, 105. EXAMPLE 6 Preparation of α-[2-(l,3-Di ydro-l,3-dioxo-2H-naphthoisoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with terr-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyI)-3-pyrroUdineacetate and 2,3-naphthalenedicarboximide, the title compound is obtained (mp 203-205 °C). IR (mineral oil) 3216, 3061, 3028, 1767, 1703, 1662, 1515, 1497, 1437, 1394, 1343, 1131, 769, 765, 616 cm "1 ; NMR (300 MHz, CDC1 3 ) δ 8.31, 7.95-8.10, 7.60-7.75, 6.90-7.35, 3.30-3.90, 3.18, 2.78, 2.35-2.50, 2.15-2.35, 1.75-2.10, 1.35-1.75, 0.82, 0.75; MS (El) mlz 541, 485, 262, 261, 245, 210, 202, 180, 154, 105, 56. EXAMPLE 7 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- α-t2-(4,5,6,7-tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3- pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-but l α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and tetrafluorophthalimide, the title compound is obtained (mp 172.5-173.5 °C). IR (mineral oil) 3216, 1724, 1712, 1664, 1639, 1514, 1503, 1418, 1341, 1301, 1156, 1038, 948, 940, 754 cm "1 ; 1H NMR (300 MHz, CDClg) δ 8.89, 7.47, 6.95-7.35, 3.35-3.80, 3.10-3.35, 2.79, 2.38, 1.30-2.30, 0.85, 0.80; MS (El) mlz 563, 507, 454, 261, 245, 202, 154, 110, 105, 104, 55. EXAMPLE 8 Preparation of α-[2-(5,6-Dichloro-l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. Following the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 4,5-dichlorophthaUmide, the title compound is obtained (mp 207-208 °C). IR (mineral oU) 3173, 3070, 1775, 1709, 1667, 1630, 1441, 1434, 1401, 1330, 1278, 1033, 749, 706, 601 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 10.18, 8.91, 7.89, 7.42, 7.00-7.40, 3.35-3.80, 3.05-3.35, 2.78, 2.38, 2.05-2.30, 1.30-2.05, 0.83, 0.78; MS (El) mlz 559, 505, 503, 262, 261, 245, 244, 230, 228, 202, 105. EXAMPLE 9 Preparation of α-[2-(5-Amino-l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with fert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 4-ammophthalimide, the title compound is obtained (mp 187-188 °C). X H NMR (300 MHz, CDClg) δ 7.56, 7.10-7.35, 7.01, 6.83, 3.30-3.70, 3.15-3.30, 2.80, 2.35-2.50, 2.15-2.30, 1.70-1.95, 1.20-1.60, 0.83, 0.75. EXAMPLE 10 Preparation of N-Hydroxy-3-(2-methylpropyl)-α-[2-(4-nitro- 1,3- dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 3-nitrophthaUmide, the title compound is obtained (mp 136-138 °C): IR (mineral oil) 3189, 3096, 3069, 1720, 1695, 1655, 1545, 1496, 1429, 1400, 1347, 1306, 1043, 749, 707 cm "1 ; 1H NMR (300 MHz, CDClg) δ 8.05-8.15, 7.85-7.95, 7.05-7.35, 3.35-3.85, 3.10- 3.25, 2.79, 2.35-2.50, 2.10-2.25, 1.75-2.05, 1.35-1.70, 0.85, 0.79; MS (FAB) mlz 537, 536, 523, 521, 505, 504, 476, 105, 104. EXAMPLE 11 Preparation of N-Hydroxy-3-(2-methylpropyl)-α-[2-(5-nitro-l,3- dinydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 4-nitrophthaUmide, the title compound is obtained (mp 161-162 °C). IR (mineral oil) 3158, 3106, 3060, 3027, 1707, 1664, 1543, 1496,- 1434, 1411, 1344, 1132, 725, 719, 700 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 8.65, 8.59, 8.04, 7.05-7.35, 3.35-3.90, 3.10-3.25, 2.79, 2.35-2.50, 2.10-2.30, 1.75-2.05, 1.35-1.75, 0.84, 0.79; MS (FAB) mlz 537, 523, 522, 504, 476, 202, 105. EXAMPLE 12 Preparation of α-[2-(4-Fluoro-l,3-dihydro-l,3-dioxo-2H-isoindol- 2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pvrrolidineacetate and 3-fluorophthalimide, the title compound is obtained (mp 145-146 °C). IR (mineral oil) 3205, 3065, 3028, 1776, 1717, 1657, 1611, 1497, 1483, 1399, 1349, 1303, 1255, 746, 701 cm '1 ; λ U NMR (300 MHz, CDClg) δ 7.55-7.80, 7.36, 6.80-7.35, 3.35-3.85, 3.05-3.30, 2.79, 2.30-2.55, 2.05-2.30, 1.70-2.00, 1.35-1.70, 0.83, 0.78; MS (El) m z 509, 477, 453, 449, 345, 262, 261, 178, 105, 104. EXAMPLE 13 Preparation of α-[2-(4,7-Difluoro-l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 3,6-difluorophthaUmide, the title compound is obtained (mp 131-132 °C). IR (mineral oU) 3196, 3029, 1779, 1721, 1657, 1495, 1421, 1395, 1359, 1263, 1256, 911, 908, 753, 697 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.10-7.45, 6.94, 3.35-3.80, 3.15-3.30, 2.79, 2.30- 2.50, 2.00-2.30, 1.75-2.00, 1.35-1.75, 0.85, 0.79; MS (El) mlz 527, 495, 471, 467, 363, 262, 261, 202, 196, 105, 104. EXAMPLE 14 Preparation of α-[2-(5-Fluoro-l,3-dihydro-l,3-dioxo-2H-isoindol- 2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. Following the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate and 4-fiuorophthaUmide, the title compound is obtained (mp 143-144 °C). IR (mineral oU) 3218, 3072, 3006, 1775, 1713, 1660, 1612, 1495, 1483, 1400, 1293, 1264, 1040, 747, 707 cm "1 ; : H NMR (300 MHz, CDClg) δ 7.83, 7.50, 6.85-7.45, 3.35-3.80, 3.05-3.25, 2.79, 2.30-2.50, 2.05-2.30, 1.75-2.00, 1.30-1.70, 0.83, 0.77; MS (El) mlz 509, 477, 453, 449, 345, 262, 261, 178, 105, 104. EXAMPLE 15 Preparation of α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)propyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrroUdineacetamide. Following the general procedure of EXAMPLE 4 and making non-critical variations but starting with tert-butyl α-(3-hydroxypropyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrrolidineacetate (prepared siπularly to that described in EXAMPLE 4, step 2) and phthalimide, the title compound is obtained (mp 113-114 °C). IR (mineral oU) 3241, 3087, 3058, 3026, 1773, 1715, 1663, 1498, 1399, 1352, 1320, 1298, 1067, 718, 604 cm "1 ; J H NMR (300 MHz, CDClg) δ 10.66, 7.75-7.85, 7.60-7.55, 6.95-7.45, 3.35-3.80, 3.10-3.25, 2.80, 2.44, 2.10-2.30, 1.85-2.00, 1.30-1.85, 0.85, 0.79; MS (El) mlz 505, 473, 445, 261, 245, 244, 202, 160, 105, 104. EXAMPLE 16 Preparation of α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)methyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. Step 1. Preparation of tert-Butyl α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate. LDA (1.50 mL, 3.0 mmol, 2.0 M in heptane THF/ethylbenzene) is added to a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 1, step 3; 1.02 g, 2.84 mmol), HMPA (0.51 mL, 2.9 mmol), and THF (10 mL) at -78 °C. The solution is stirred at -78 °C for 30 minutes and then a solution of N-(bromomethyl)ph1±ιaJimide (0.887 g, 3.69 mmol) and THF (4.0 mL) is added. The solution is stirred at -78 °C for 1 hour and then aUowed to warm slowly to room temperature overnight. Aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (3:1 hexane:EtOAc) gives 374 mg (25%) of the title compound as a white solid (mp 96-98 °C). IR (mineral oU) 1772, 1753, 1724, 1713, 1668, 1435, 1403, 1309, 1234, 1143, 1094, 737, 725, 714, 697 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.70-7.90, 7.15-7.35, 4.07, 3.86, 3.55-3.70, 3.35- 3.50, 3.25-3.35, 3.11, 2.84, 2.50-2.65, 1.75-1.90, 1.60-1.75, 1.20, 0.85-0.95; MS (FAB) mlz 519, 464, 463, 445, 159, 105, 57, 41, 29. Step 2. Preparation of α-[2-(l,3-DU ydro-l,3-dioxo-2H-isoindol-2-yl)methyl]-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pvrroUdineacetic Acid. TFA (5.0 mL) is added to a solution of tert-butyl α-t2-(l,3-dihydro-l,3-dioxo- 2H-isoindol-2-yl)methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (374 mg, 0.721 mmol) and CH 2 C1 2 (5.0 mL) at 0 °C. The solution is stirred for 2 hours at 0 °C and 2 hours at room temperature. The solution is concentrated and reconcentrated twice more from CH^Lg (2 X 30 mL). Aqueous workup (CH 2 C1 2 , MgS0 4 ) provides 291 mg (87%) of the title compound as an oU which is carried on crude. X H NMR (300 MHz, CDClg) δ 7.65-7.95, 7.05-7.35, 3.90-4.05, 3.64, 3.35-3.55, 3.12, 2.80-3.05, 2.83, 2.10-2.40, 1.50-1.80, 0.90, 0.86. Step 3. Preparation of α-t2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)methyl]-N- hydroxy-3-(2-methylpropy l)-2-oxo- 1-( 2-phenylethyl)-3- pyrroUdineacetamide. EDC (129 mg, 0.672 mmol) is added to a solution of α-[2-(l,3-dihydro-l,3- dioxo-2H-isoindol-2-yl)methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetic acid (270 mg, 0.584 mmol), CH^C^ (5.7 mL), DMF (1.4 mL), HOBT (78.9 mg, 0.584 mmol), and N-methylmorpholine (74 μL, 0.67 mmol) at 0 °C. The solution is stirred for 5 minutes at 0 °C and for 1 hour at room temperature. Hydroxylamine hydrochloride (80.9 mg, 1.16 mmol) and N-methylmorphoUne (0.13 mL, 1.2 mmol) are added and the mixture stirred overnight at room temperature. Aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by flash chromatography (EtOAc) provides 160 mg of the hydroxamate as a white foam which is crystaUized from ether/hexane to give 129 mg (46%) of the title compound as a white crystalline material which is a 4.25:1 mixture of diastereomers (mp 170-171 °C). IR (mineral oU) 3194, 3105, 3050, 3028, 1773, 1709, 1665, 1644, 1496, 1434, 1409, 1393, 1309, 721, 701 cm '1 ; X H NMR (300 MHz, CDClg) δ 10.97, 7.65-7.90, 7.10-7.35, 3.65-3.90, 3.20-3.55, 2.75-2.95, 2.35-2.50, 2.00-2.15, 1.50-1.85, 0.87; MS (FAB) mlz 478 477, 445, 261, 202, 160, 105, 43. EXAMPLE 17 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-(2-thienylthio)ethyl]-3-pyrroUdineacetamide. Step 1. Preparation of tert-Butyl α-[2-(Methanesulfonyloxy)ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate. Methanesulfbnyl chloride (0.29 mL, 3.7 mmol) is added to a solution of tert- butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (EXAMPLE 4, step 2; 1.36 g, 3.37 mmol), triethylamine (0.52 mL, 3.7 mmol) and CH 2 C1 2 (8 mL) at 0 °C. The mixture is stirred for 2 hours, washed with saturated NaHCOg (2 x 10 mL), water (10 mL), dried (MgS0 4 ), filtered, and concentrated to give 1.22 g (75%) of the title compound as a Ught yeUow oU. X H NMR (300 MHz, CDClg) δ 7.15-7.35, 4.10-4.30, 3.55-3.70, 3.35-3.50, 3.20- 3.30, 3.01, 2.82, 2.55, 2.10-2.35, 1.85-2.05, 1.70-2.05, 1.40-1.65, 1.44, 0.87, 0.83. Step 2. Preparation of tert-Butyl 3-(2-Methylpropyl)-2-oxo-l-(2-phenylethyl)-α- [2-(2-thienylthio)ethyl]-3-pyrrolidineacetate. Sodium hydride (60%, 41 mg, 1.0 mmol) is added to a solution of thiophenethiol (118 mg, 1.02 mmol), THF (25 mL) and DMF (25 mL) at 0 °C. The mixture is stirred for 30 minutes at 0 °C and a solution of tert-butyl α-[2- (metiιanesulfonyloxy)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (490 mg, 1.02 mmol) in THF (15 mL) is added. The solution is aUowed to warm slowly and is stirred at room temperature overnight. Concentration, aqueous workup (EtOAc, MgS0 4 ), and purification by flash chromatography (25% EtOAc/hexane) gives 361 mg (71%) of title compound as a colorless oU. IR (liq.) 2956, 2930, 2868, 1720, 1685, 1497, 1454, 1428, 1367, 1276, 1258, 1217, 1147, 847, 700 cm '1 ; X H NMR (300 MHz, CDClg) δ 7.15-7.40, 7.10-7.15, 6.90-7.00, 3.55-3.65, 3.30- 3.45, 3.15-3.25, 2.75-2.90, 2.60-2.75, 2.58, 2.25-2.40, 1.80-2.00, 1.65-1.80, 1.35-1.65, 1.39, 0.84, 0.80; MS (El) m lz 501, 428, 386, 331, 330, 303, 247, 246, 212, 105, 57. Step 3. Preparation of 3-(2-Methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(2- thienylthio)ethyl]-3-pyrroUdineacetic Acid. A solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(2- thienylthio)ethyl]-3-pyrroUdineacetate (338 mg, 0.674 mmol), trifluoroacetic acid (3 mL), and CH 2 C1 2 (3 mL) is stirred at 0 °C for 15 minutes and at room temperature for 1.5 hour. Concentration and aqueous workup (CH 2 C1 2 , MgS0 4 ) gives 287 mg (96%) of the title compound as a colorless oU. IR (liq.) 2958, 2931, 2870, 1736, 1683, 1620, 1498, 1480, 1465, 1454, 1444, 1263, 1216, 746, 700 cm *1 ; NMR (300 MHz, CDClg) δ 13.75, 7.35-7.40, 7.05-7.35, 6.95-7.05, 3.70-3.85, 3.35-3.50, 3.15-3.35, 2.80-2.95, 2.55-2.80, 2.00-2.15, 1.35-1.90, 0.91, 0.84; MS (El) mlz 445, 331, 330, 258, 247, 246, 228, 212, 156, 105, 55. Step 4. Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- α-[2-(2-t enylthio)ethyl]-3-pyrτoUdineacetamide. A solution of HOBT (83 mg, 0.62 mmol) in DMF (1.3 mL) is added to a solution of 3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(2-thienylthio)ethyl]-3- pyrroUdineacetic acid (259 mg, 0.581 mmol) in CH^CL^ (6 mL) at room temperature. The solution is cooled to 0 °C. To this is added 4-methylmorpholine (77 μL, 0.70 mmol) and EDC (134 mg, 0.697 mmol). The solution is stirred at 0 °C for 1 hour and then a mixture of hydroxylamine hydrochloride (57 mg, 0.87 mmol), 4- methylmorpholine (96 μL, 7.4 mmol), and DMF (0.8 mL) is added. The mixture is stirred overnight at room temperature and concentrated. Purification of the residue by flash chromatography (50% EtOAc/hexane) and CrystaUization (ether/hexane) gives 95 mg (36%) of the title compound as a white soUd (mp 109-110 °C). IR (mineral oU) 3202, 3096, 3081, 3023, 1652, 1496, 1441, 1432, 1314, 1294, 1280, 1222, 751, 717, 702 cm '1 ; 1H NMR (300 MHz, CDClg) δ 10.55, 7.05-7.40, 6.90-7.00, 3.50-3.65, 3.05-3.25, 2.70-2.95, 2.50-2.70, 1.95-2.25, 1.35-1.95, 0.85, 0.80; MS (El) mlz 460 345, 284, 262, 261, 228, 105, 81, 79, 55. EXAMPLE 18 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-(2-tnienylthio)propyl]-3-pyrroUdineacetamide. FoUowing the general procedure of EXAMPLE 17 and making non-critical variations but starting with tert-butyl α-(3-hydroxypropyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate, the title compound is obtained (mp 104-105 °C). IR (mineral oil) 3211, 3101, 3069, 3028, 1667, 1653, 1497, 1428, 1399, 1310, 1298, 1293, 1249, 760, 710 cm "1 ; 1H NMR (300 MHz, CDClg) δ 6.70-7.75, 3.05-3.95, 2.50-3.05, 1.15-2.50, 0.87, 0.82; MS (El) mlz A, 442, 386, 359, 326, 298, 244, 202, 105, 55. EXAMPLE 19 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-(2-thienylthio)methyl]-3-pyrroUdineacetamide. Following the general procedure of EXAMPLE 17 and making non-critical variations but starting with tert-butyl α-(l-hydroxymethyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate, the title compound is obtained (mp 145-146 °C). IR (mineral oU) 3177, 3085, 3027, 1664, 1641, 1496, 1408, 1297, 1274, 1218, 1029, 1000, 845, 746, 702 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.68, 7.15-7.40, 6.90-7.15, 3.35-3.70, 2.55-3.30, 2.05-2.25, 1.65-1.70, 1.25-1.60, Major diastereomer peaks. 0.80, 0.71, Minor diastereomer peaks. 0.75, 0.61; MS (El) mlz 446, 246, 245, 203, 202, 154, 105. EXAMPLE 20 Preparation of N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo- 1,3-pyrroUdinediacetamide. Step 1. Preparation of l-Trimethylsilyl-2-pyrroUdinone. ChlorotrimethylsUane (TMSC1, 56.0 mL, 441 mmol) is added dropwise to a solution of 2-pyrroUdinone (30.4 mL, 400 mmol), triethylamine (70.0 mL, 502 mmol) and toluene (400 mL) at room temperature. After stirring at room temperature with a mechanical stirrer for 20 minutes, the mixture is heated at 50 °C for 4 hours. After cooUng, the mixture is diluted with hexane (300 mL) and stirred for 30 minutes at room temperature. The mixture is filtered and the filtrate concentrated. Distillation of the residue (1 mm, 68-74 C C) gives 50.0 g (94%) of the title compound as an oil. X H NMR (300 MHz, d 5 -pyridine) δ 3.17, 2.26, 1.70-1.85, 0.32. Step 2. Preparation of 3-(2-methylpropyl)-2-pyrroUdinone. A solution of LDA (2.0 M, 111 mL, 222 mmol) and THF (300 mL) is cooled to -78 °C and a solution of l-trimethylsUyl-2-pyrroUdinone (29.4 g, 221 mmol) in THF (145 mL) is added. After stirring for 45 minutes at -78 °C, the enolate solution is added via cannula over 1 hour to a solution of l-iodo-2-methylpropane (42.7 g, 232 mmol) in THF (200 mL) at -78 °C. The solution is aUowed to warm slowly and stirred at room temperature overnight. The reaction is quenched by the addition of 50 mL of acetic acid. Aqueous workup (EtOAc, MgS0 4 ) and purification by column chromatography (30-→100% EtOAc/hexane) gives 12.8 g of the title compound as an oil. X H NMR (300 MHz, CDClg) δ 6.30, 3.10-3.30, 2.05-2.35, 1.45-1.80, 1.00-1.20, 0.81, 0.76. Step 3. Preparation of 3-(2-methylpropyl)-l-trimethylsilyl-2-pyrrolidinone. TMSC1 (2.2 mL, 18 mmol) is added dropwise to a solution of 3-(2- methylpropyl)-2-pvrroUdinone (2.25 g, 15.9 mmol), triethylamine (2.7 mL, 19 mmol), and toluene (16 mL) at room temperature. The mixture is heated at 40 °C for 3 hours and diluted with hexane (50 mL). After stirring for 10 minutes at 0 °C, the mixture is filtered and the filtrate concentrated. DistiUation (1 mm, 62-68 °C) of the residue gives 2.40 g (71%) of the title compound as an oil. 1H NMR (300 MHz, CDClg) δ 3.05-3.30, 2.20-2.35, 2.05-2.20, 1.45-1.70, 1.05- 1.15, 0.82, 0.78, 0.15. Step 4. Preparation of 3-(2-MethylpropyI)-3-(propen-2-yl)-2-pyrroUdinone. A solution of 3-(2-methylpropyl)-l-trimethylsUyl-2-pyrroUdinone (10.2 g, 47.8 mmol) and THF (153 mL) is cooled to -78 °C, and LDA (2.0 M, 26.3 mL, 52.6 mmol) is added. The solution is stirred at -78 °C for 30 minutes and then allyl bromide (5.0 mL, 57 mmol) is added. The solution is allowed to warm to 5 °C over 2.5 hours, and is then stirred at 5 °C for 1 hour. After quenching with saturated aqueous ammonium chloride (25 L), aqueous workup (EtOAc, MgS0 4 ) and purification by column chromatography (1:9:10 v/v CH 2 Cl 2 :EtOAc:hexane) provides 7.76 g (90%) of the title compound as an oil. IR (liq.) 3241, 3077, 2957, 2929, 2902, 2873, 1708, 1693, 1640, 1440, 1284, 1277, 1264, 1251, 842 cm '1 ; 2 H NMR (300 MHz, CDClg) δ 6.43, 5.65-5.85, 5.00-5.15, 3.15-3.35, 2.00-2.40, 1.65-1.85, 1.40-1.60, 0.92; MS (El ) mlz 138, 125, 124, 98, 73, 60, 55, 45, 43, 41. Step 5. Preparation of Ethyl 3-(2-methylpropyl)-2-oxo-3-(propen-2-yl)-l- pyrroUdineacetate. A solution of potassium bis(trimethylsUyl)amide (0.5 M in toluene, 16.4 mL, 8.19 mmol) is cooled to 0 °C, and a solution of 3-(2-methylpropyl)-3-(propen-2-yl)-2- pyrroUdinone (1.24 g, 6.82 mmol) in THF (10 mL) is added dropwise over 2 minutes After stirring at 0 °C for 40 minutes, ethyl bromoacetate (0.91 mL, 8.2 mmol) is added. The reaction is stirred at 0 °C for 3 hours and for 1 hour at room temperature. After quenching with saturated aqueous ammonium chloride (10 mL), aqueous workup (EtOAc, MgSO 4 ) and purification by column chromatography (1:9:10 v/v CH 2 Cl 2 :EtOAc:hexane) provided 1.66 g (91%) of the title compound as an oU. E (liq.) 2957, 2930, 2906, 2872, 1750, 1692, 1462, 1440, 1375, 1296, 1281, 1252, 1196, 1028, 916 cm "1 ; 1H NMR (300 MHz, CDClg) δ 5.50-5.75, 4.90-5.05, 4.00-4.15, 3.93, 3.15-3.30, 2.15-2.30, 2.00-2.15, 1.80-2.00, 1.55-1.75, 1.30-1.50, 1.16, 0.82, 0.77; MS (El ) mlz 212, 211, 210, 194, 152, 138, 137, 110. Step 6. Preparation of N-Methyl-3-(2-methylpropyl)-2-oxo-3-(propen-2-yl)-l- pyrroUdineacetamide. Ethyl 3-(2-methylprOpyl)-2-oxo-3-(propen-2-yl)-l-pyrroUdineacetate (500 mg, 1.87 mmol) is stirred in a saturated solution of methylamine in EtOH (50 mL) at room temperature overnight. The solution is concentrated and purified by column chromatography (1:12:8 v/v CH 2 Cl 2 :EtOAc:hexane) to give 401 mg (85%) of the title compound as an oil. IR (liq.) 3308, 2955, 2928, 2872, 1662, 1560, 1495, 1464, 1443, 1413, 1279, 1263, 1252, 915, 842 cm "1 ; λ U NMR (300 MHz, CDClg) δ 6.32, 5.50-5.75, 4.90-5.10, 3.79, 3.28, 2.67, 2.17, 1.85-2.10, 1.55-1.75, 1.30-1.55, 0.84, 0.77; MS (ED mlz 252, 221, 210, 209, 196, 194, 166, 165, 152, 138, 124, 110, 95, 73. Step 7. Preparation of l-(N-Methylacetamide)-3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetic Acid. Ruthenium(IV) oxide hydrate (15 mg, 0.11 mmol) is added at room temperature to a mixture of sodium periodate (944 mg, 4.41 mmol) in acetonitrile (1.9 mL), carbon tetrachloride (0.9 mL) and water (2.0 mL). After stirring for 10 minutes, sodium bicarbonate (2.32 g, 27.6 mmol) is added, followed by a solution of N-methyl-3-(2-methylpropyl)-2-oxo-3-(propen-2-yl)- 1-pyrroUdineacetamide ( 139 mg, 0.552 mmol) in acetonitrile (2.0 mL). Sodium periodate (approximately 150 mg) is added until the black mixture turnes Ught green. After 5 minutes the mixture is poured into 100 mL of water. The pH of the mixture is adjusted to pH 2 (pH paper) with concentrated HC1. The acidic solution is extracted with CH 2 C1 2 and EtOAc. The combined organic layers are dried (MgSO 4 ), filtered, and concentrated to provide 157 mg (100%) of the title compound as an oU. -Η NMR (300 MHz, CDClg) δ 7.09, 4.30-4.45, 3.20-3.50, 2.67, 2.63, 1.95-2.25, 1.55-1.70, 1.30-1.45, 0.84, 0.78. Step 8. Preparation of N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-l,3- pyrroUdinediacetamide. EDC (1.14 g, 5.95 mmol) is added to a solution of l-(N-methylacetamide)-3- (2-methylpropyl)-2-oxo-3-pyrrolidineacetic acid (1.34 g, 4.96 mmol), HOBT (710 mg, 5.26 mmol) and 4-methylmorpholine (0.65 mL, 5.9 mmol) in CH 2 C1 2 (51 mL) and DMF (10 mL) at 0 °C. The solution is stirred at 0 °C for 1 hour, and then a mixture of hydroxylamine hydrochloride (517 mg, 7.44 mmol) in DMF (7 mL) is added foUowed by 4-methylmorpholine (0.82 mL, 7.4 mmol). After stirring for 7 days at room temperature, the mixture is concentrated under high vacuum and purified by column chromatography (3% MeOH/CH 2 Cl 2 ). CrystalUzation from Et 2 O/hexane provides 211 mg (15%) of the title compound as a white soUd (mp 145-147 °C). IR (mineral oil) 3259, 3199, 3097, 3017, 1662, 1564, 1522, 1501, 1412, 1405, 1313, 1297, 1275, 750, 724 cm '1 ; 1H NMR (300 MHz, CDClg/CDgOD) δ 4.25-4.45, 3.05-3.50, 2.74, 2.32, 1.90- 2.20, 1.55-1.75, 1.30-1.50, 0.87, 0.79; MS (El) mlz 285, 254, 229, 226, 194, 180, 169, 166, 152, 138, 124, 110, 55. EXAMPLE 21 Preparation of N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo- α phenylmethyl)- 1 , 3-pyrroUdinediacetamide. Step 1. Preparation of Ethyl 3-(2-methylpropyl)-2-oxo-α-(phenylmethyl)-3- (propen-2-yl)-l-pyrroUdineacetate. A solution of ethyl 3-(2-methylpropyl)-2-oxo-3-(propen-2-yl)-l- pyrroUdineacetate (Example 20, step 5; 1.63 g, 6.10 mmol) and THF (15 mL) is cooled to -78 °C and LDA (2.0 M, 3.2 mL, 6.4 mmol) is added. The solution is stirred at -78 °C for 30 minutes and then benzyl bromide (0.80 mL, 6.7 mmol) is added. The solution is aUowed to warm to 0 °C over 2 hours, and then stirred at 0 °C for 1 hour. After quenching with saturated aqueous ammonium chloride (10 mL), aqueous workup (EtOAc, MgS0 4 ) and purification by column chromatography (10% EtOAc/hexane) provided 1.94 g (89%) of the title compound as an oU in a 1:1 mixture of diastereomers. IR (liq.) 2975, 2956, 2930, 2906, 1739, 1689, 1499, 1455, 1425, 1266, 1207, 1192, 1032, 915, 698 cm '1 ; 1H NMR (300 MHz, CDClg) δ 7.05-7.30, 5.55-5.75, 4.85-5.20, 4.65-4.85, 4.00- 4.20, 3.00-3.40, 2.80-2.95, 2.12, 1.50-1.95, 1.30-1.45, 1.15-1.30, 1.00-1.15, 0.83, 0.79, 0.66, 0.54; MS (El) mlz 357, 301, 238, 228, 284, 282, 267, 266, 210, 200, 176, 164, 125, 102, 91. Step 2. Preparation of N-Methyl-3-(2-methylpropyl)-2-oxo-α-(phenylmethyl)-3- (propen-2-yl)- 1-pyrroUdineacetamide. Methylamine gas is bubbled through a solution of ethyl 3-(2-methylpropyl)-2- oxo-α-(phenylmethyl)-3-(propen-2-yl)-l-pyrrolidineacetate (3.40 g, 9.51 mmol) in EtOH (120 mL) for 30 minutes at room temperature, and the solution is stirred at room temperature overnight. The solution is concentrated and purified by flash chromatography (1:6:11→1:10:9 v/v CH 2 Cl 2 :EtOAc:hexane) to give 3.01 g (92%) of the title compound as a solid (mp 91-92 °C) which is a ca. 1:1 mixture of diastereomers. IR (mineral oil) 3315, 1684, 1654, 1584, 1562, 1499, 1442, 1414, 1296, 1278, 1264, 1225, 913, 744, 708 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.10-7.30, 6.15-6.40, 5.50-5.70, 5.10-5.30, 4.95- 5.10, 4.75-4.95, 3.15-3.35, 2.90-3.10, 2.72, 2.71, 1.95-2.20, 1.50-1.95, 1.15-1.50, 0.86, 0.78, 0.74, 0.64; MS (El) mlz 342, 300, 284, 267, 251, 242, 200, 162, 132, 105, 91, 81, 73, 67. Step 3. Preparation of N 1 -Methylacetamide-3-(2-methylpropyl)-2-oxo-α - (phenylmethyl)-3-pyrroUdineacetic Acid. Ruthenium(IV) oxide hydrate (29 mg, 0.22 mmol) is added to a mixture of sodium periodate (1.85 g, 8.65 mmol) in acetonitrile (3.8 mL), carbon tetrachloride (1.8 mL), and water (3.9 mL) at room temperature. After stirring for 10 minutes, sodium bicarbonate (4.55 g, 54.2 mmol) is added, followed by a solution of N-methyl- 3-(2-methylpropyl)-2-oxo-α-(phenylmethyl)-3-(propen-2-yl)-l-pyrroUdineacetamide (371 mg, 1.08 mmol) in acetonitrile (4.0 mL). Sodium periodate (approximately 300 mg) is added until the black mixture turns Ught green. After 5 minutes, the mixture is poured into 100 mL of water. The mixture is extracted with EtOAc (2 x 50 mL). The pH of the aqueous mixture is adjusted to pH 2 (pH paper) with concentrated HCl. The acidic mixture is extracted with CH^CL^ and EtOAc, and these layers are combined with the original EtOAc extracts, dried (MgS0 4 ), filtered, and concentrated to give 300 mg of the crude acid as a dark brown oU. This material is dissolved in 15% NaOH (10 mL) and extracted with Et 2 0 (3 x 20 mL). These Et^O layers are discarded. The pH of the aqueous layer is adjusted to pH 2 (pH paper) with concentrated HCl. The acidic layer is extracted with EtOAc (3 x 30 mL). the combined EtOAc layers dried (MgS0 4 ), filtered, and concentrated to give 230 mg (59%) of the title compound as an oil as a 1:1 mixture of diastereomers. IR (mineral oil) 3358, 3087, 3064, 3029, 1721, 1649, 1550, 1498, 1441, 1413, 1297, 1272, 1233, 1192, 700 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.05-7.40, 6.55-6.70, 5.10, 4.56, 3.64, 3.20-3.55, 2.70-3.05, 2.30-2.70, 1.75-2.20, 1.55-1.75, 1.49, 1.05-1.40, 0.80-1.00, 0.90, 0.83, 0.69, 0.66; MS (El) mlz 360, 336, 303, 302, 284, 269, 256, 246, 228, 200, 162, 161, 132, 105, 91. Step 4. Preparation of N -Hydroxy-N -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide. EDC (1.08 g, 5.66 mmol) is added to a solution of N 1 -methylacetamide-3-(2- methylpropyl)-2-oxo-α -(phenylmethyl)-3-pyrrolidineacetic acid (1.70 g, 4.72 mmol), HOBT (676 mg, 5.00 mmol) and 4-methylmorpholine (0.52 mL. 4.7 mmol) in CH 2 C1 2 (49 mL) and DMF (10 mL) at 0 °C. The solution is stirred at 0 °C for 1 hour and then a mixture of hydroxylamine hydrochloride (491 mg, 7.08 mmol) in DMF (7 mL) is added, foUowed by 4-methylmorphoUne (0.79 mL, 7.1 mmol). The mixture is stirred at room temperature overnight and concentrated under high vacuum. The residue is dissolved in 15% NaOH (13 mL) and extracted with EtOAc (3 x 20 mL). These EtOAc layers are discarded. The pH of the aqueous layer is adjusted to pH 2 (pH paper) with 6 N HCl. The acidic layer is extracted with CH 2 C1 2 (3 x 30 mL), the combined CH 2 C1 2 layers dried (MgSO 4 ), filtered, and concentrated. Purification by column chromatography (5 % MeOH/C^CL^) and crystallization from Et j ^O/hexane provided 255 mg (14%) of the title compound as a white soUd (mp 166- 168 °C) as a mixture of diastereomers. IR (mineral oU) 3373, 3199, 3087, 3064, 3027, 1686, 1667, 1634, 1546, 1498, 1404, 1356, 1303, 742, 697 cm "1 ; 2 H NMR (300 MHz, CDCl 3 /CD 3 OD) major diastereomer, key peaks: δ 4.48, 2.76, 0.89, 0.81. Minor diastereomer, key peaks: δ 5.05, 2.82, 0.69, 0.62; MS (El) mlz 375, 344, 317, 316, 285, 284, 256, 132, 91. EXAMPLE 22 Preparation of α-[2-(l,3-D ydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)- 3-pyrroUdineacetamide. Step 1. Preparation of N-tert-Butyloxycarbonyl-2-pyrroUdinone. A solution of di-tert-butyl dicarbonate (28.2 g, 129 mmol) in dry CH 2 C1 2 (80 mL) is added to a stirred solution of 2-pyrroUdinone (10.0 g, 117 mmol) and DMAP (200 mg, catalytic amount) in dry CH 2 C1 2 (230 mL) over 10 minutes. After 16 hours, the solution is diluted with H 2 O (150 mL) and extracted with EtOAc (4 x 100 mL). The organic layers are combined, dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to give a red oU. The oU is purified by siUca gel chromatography (200 g SG, 40% EtOAc/hexane) to yield 20.1 g (93%) of the title compound as a gold oU. IR (Uq.) 2980, 1786, 1752, 1714, 1459, 1394, 1368, 1315, 1256, 1228, 1154, 1045, 1018, 858, 778 cm "1 ; 1H NMR (300 MHz, CDClg) δ 3.74, 2.50, 1.90-2.05, 1.52; MS (FAB) mlz 186, 131, 130, 112, 86, 57, 41. Step 2. Preparation of N-tert-Butyloxycarbonyl-3-(2-methylpropen-2-yl)-2- pyrroUdinone. A solution of N-tert-butyloxycarbonyl-2-pyrroUdinone (10.0 g, 54.0 mmol) and HMPA (9.40 mL, 54.0 mmol) in dry THF (200 mL) is cooled to -78 °C and treated drop-wise over 6.5 minutes with Uthium diisopropylamide (LDA, 29.7 mL, 59.4 mmol, 2 M in heptane THF/ethylbenzene). After 30 minutes at -78 °C, 3-bromo-2- methylpropene (6.53 mL, 64.8 mmol) is added. The solution is maintained at -78 °C under N 2 for 6 hours, and is then quenched with saturated NH 4 C1 (100 mL). The solution is warmed to 0 °C and diluted with H 2 O (300 mL). The crude olefin is extracted into EtOAc (3 x 200 mL), dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to give an oil. The oU is purified by silica gel chromatography (350 g gel; 20% EtOAc/hexane) to yield 7.75 g (60%) of the title compound as a golden oU. IR (liq.) 2980, 2934, 2909, 1785, 1749, 1716, 1457, 1394, 1368, 1322, 1295, 1251, 1227, 1155, 779 cm "1 ; 1H NMR (300 MHz, CDClg) δ 4.79, 4.71, 3.70-3.80, 3.50-3.65, 2.60-2.75, 1.95- 2.20, 1.72, 1.55-1.75, 1.52; MS (El) mlz 239, 183, 166, 165, 139, 57. Step 3. Preparation of tert-Butyl N-tert-Butyloxycarbonyl-3-(2-methylpropen-2- yl)-2-oxo-3-pyrrolidineacetate. A solution of N-tert-butyloxycarbonyl-3-(2-methylpropen-2-yl)-2-pyrrolidinone (7.39 g, 30.8 mmol) in dry THF (125 mL) is cooled to -78 °C and treated drop-wise with LDA (17.0 mL, 33.9 mmol). After 30 minutes at -78 °C, tert-butyl bromoacetate (5.46 mL, 37.0 mmol) is added. The solution is maintained at -78 °C for 6 hours and then quenched with saturated NH 4 C1 (50 mL). The solution is warmed to 0 °C and dfluted with H 2 0 (50 mL). The crude ester is extracted into EtOAc (3 x 100 mL), dried over anhydrous Na 2 S0 , filtered, and concentrated under reduced pressure to give an orange oU. The material is purified by silica gel chromatography (2 columns: 250 g, 100 g SG, 10% EtOAc hexane) to yield 7.69 g (71%) of the title compound as a golden oU. IR (liq.) 2980, 2934, 2918, 1786, 1748, 1718, 1457, 1394, 1369, 1315, 1258, 1208, 1155, 965, 853 cm "1 ; 1H NMR (300 MHz, CDClg) δ 4.90, 4.78, 3.50-3.75, 2.53, 2.30, 2.05-2.20, 1.72, 1.51, 1.42; MS (El) mlz 353, 297, 280, 241, 224, 223, 196, 180, 57. Step 4. Preparation of tert-Butyl N-tert-Butyloxycarbonyl-3-(2-methylpropyl)-2- oxo-3-pyrroUdineacetate . A solution of tert-butyl N-tert-butyloxycarbonyl-3-(2-methylpropen-2-yl)-2-oxo- 3-pyrroUdineacetate (7.90 g, 22.4 mmol) in EtOH (150 mL) is treated with 10% paUadium on carbon (1.98 g, 25% by weight) and hydrogenated in a Parr flask at 45 psi for 16 hours at room temperature. The mixture is filtered through celite; the residual cake is washed with EtOH (2 x 100 mL), MeOH (2 x 100 mL), and CHgClg (100 mL). The filtrate is concentrated under reduced pressure to yield 7.86 g (99%) of the title compound as a thick, cloudy oil. IR (liq.) 2978, 2934, 1786, 1749, 1717, 1476, 1458, 1393, 1369, 1317, 1258, 1207, 1155, 1117, 969 cm "1 ; 1H NMR (300 MHz, CDClg) δ 3.55-3.80, 2.53, 2.05-2.20, 1.90-2.05, 1.60-1.80, 1.40-1.60, 1.52, 1.42, 0.91, 0.90; MS (FAB) mlz 356, 300, 244, 226, 200, 182, 154, 57. Step 5. Preparation of tert-Butyl N-tert-Butyloxycarbonyl-3-(2-methylpropyl)-2- oxo-α-(propen-2-yl)-3-pyrroUdineacetate. A solution of tert-butyl N-tert-butyloxycarbonyl-3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetate (3.65 g, 10.3 mmol) in dry THF (45 mL) is cooled to -78 °C and treated drop-wise with LDA (5.70 mL, 11.3 mmol). After 30 minutes at -78 °C, aUyl bromide (1.10 mL, 12.4 mmol) is added. The solution is maintained at -78 °C for 3 hours, and is then aUowed to slowly warm to room temperature under N 2 . After 12 hours, the solution is quenched with saturated NH 4 C1 (10 mL) and diluted with H 2 0 (50 mL). The crude lactam is extracted into EtOAc (3 x 100 mL). The organic extracts are combined, washed with brine (50 mL), dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to give 4.72 g of gold oU. The oil is purified by silica gel chromatography (300 g SG, 5% EtOAc/hexane) to yield 2.98 g (73%) of the title compound as a clear, pale gold oU as a mixture of diastereomers. IR (liq.) 2979, 2961, 2934, 1785, 1748, 1719, 1457, 1393, 1369, 1315, 1257, 1207, 1156, 1125, 851 cm "1 ; X H NMR (300 MHz, CDClg, key peaks of the major diastereomer): δ 5.60- 5.85, 4.95-5.15, 3.55-3.75, 2.64, 2.20-2.50, 1.35-1.90, 1.52, 1.42, 0.91, 0.88; MS (FAB) mlz 396, 340, 285, 284, 266, 222, 57, 41, 29. Step 6. Preparation of tert-Butyl 3-(2-Methylpropyl)-2-oxo-α-(propen-2-yl)-3- pyrroUdineacetate. A solution of tert-butyl N-tert-butyloxycarbonyl-3-(2-methylpropyl)-2-oxo-α- (propen-2-yl)-3-pyrroUdineacetate (5.40 g, 13.7 mmol) in MeOH (70 mL) is treated with magnesium methoxide (74.7 mL, 68.5 mmol, 10.3 wt % in MeOH). The resultant solution is stirred under N 2 at room temperature for 16 hours. The solution is quenched with 1:1 glacial AcOH/H 2 0 (100 mL). The solution is reduced to a minimal volume under reduced pressure, and the unprotected lactam is extracted into CH 2 C1 2 (3 x 100 mL). The organic layers are combined, washed with saturated NH 4 C1 (100 mL), brine (100 mL), dried over anhydrous Na<2S0 , filtered, and concentrated under reduced pressure to give 4.75 g of a gold oil. The oU is purified by siUca gel chromatography (100 g SG, 25% EtOAc hexane) to yield 3.85 g (96%) of the title compound as an off-white, low-melting soUd. IR (mineral oU) 3206, 3105, 1720, 1701, 1352, 1299, 1268, 1255, 1231, 1162, 1153. 1125, 923 cm "1 ; l rl NMR (300 MHz, CDClg) δ 6.28, 5.65-5.85, 4.90-5.15. 3.20-3.40, 2.60, 2.20- 2.60, 1.85-2.00, 1.65-1.80, 1.35-1.65, 1.41, 0.93, 0.91; MS (FAB) mlz 296, 240, 222, 194, 57. Step 7. Preparation of tert-Butyl 3-(2-Methylpropyl)-2-oxo-l-(phenylmethyl)-α- (propen-2-yl)-3-pyrroUdineacetate. A cold (0 °C) solution of tert-butyl 3-(2-methylpropyl)-2-oxo-α-(propen-2-yl)-3- pyrroUdineacetate (1.11 g, 3.76 mmol) in dry THF (25 mL) is treated with NaH (60% dispersion in mineral oU, 226 mg, 5.64 mmol) in one portion. After 30 minutes, benzyl bromide (537 μL, 4.51 mmol) is added. The solution is aUowed to slowly warm to room temperature, stirring under N 2 overnight. The mixture is quenched with H 2 O (25 mL) and extracted with EtOAc (3 x 25 mL). The organic extracts are combined, washed with brine (25 mL), dried over anhydrous Na 2 S0 , filtered, and concentrated under reduced pressure to yield 1.70 g of yeUow oil. The oil is purified by silica gel chromatography (30 g SG, 10% EtOAc/hexane) to give 1.37 g (94%) of the title compound as a clear, colorless oil. IR Qiq.) 2977, 2957, 2930, 2870, 1721, 1687, 1496, 1454, 1440, 1367, 1287, 1260, 1238, 1153, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.20-7.35, 5.65-5.85, 4.95-5.15, 4.41, 3.05-3.30, 2.62, 2.20-2.55, 1.50-1.85, 1.41, 0.89, 0.87; MS (El) mlz 385,329, 312, 232, 231, 188, 91, 57. Step 8. Preparation of tert-Butyl α-(2-Hydroxyethyl)-3-(2-methylpropyl)-2-oxo- l-(phenylmethyl)-3-pyrroUdineacetate. Ozone is bubbled through a cold (-78 °C) solution of tert-butyl 3-(2- methylpropyl)-2-oxo-l-(phenylmethyl)-α-(propen-2-yl)-3-pyrrolidineacetate (1.32 g, 3.42 mmol) in EtOH (30 mL). After purging the solution with N 2 , sodium borohydride (195 mg, 5.14 mmol) is added in one portion (at -78 °C). The solution is allowed to slowly warm to room temperatuare under N 2 overnight. The reaction mixture is concentrated to a white soUd, diluted with H 2 0 (10 mL) and extracted with EtOAc (3 x 25 mL). The organic extracts are combined, washed with brine (25 mL), dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to yield 1.37 g of a clear, colorless oU. The oil is purified by siUca gel chromatography (50 g SG, 20% EtOAc/hexane) to give 850 mg (64%) of the title compound as a clear, colorless oU, which is a single diastereomer. IR (liq.) 2956, 2930, 2870, 1771, 1720, 1684, 1497, 1464, 1454, 1441, 1367, 1286, 1261, 1154, 701 cm "1 ; rl NMR (300 MHz, CDClg) δ 7.20-7.40 4.42, 3.55-3.80, 3.10-3.30, 2.70, 2.35- 2.50, 1.90-2.05, 1.50-1.90, 1.44, 0.88, 0.87; MS (El) mlz 389, 333, 287, 259, 258, 232, 230, 140, 119, 91. Step 9. Preparation of tert-Butyl α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-3- pyrroUdineacetate. A solution of tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (phenylmethyl)-3-pyrroUdineacetate (435 mg, 1.12 mmol) in dry THF (10 mL) is treated with triphenylphosphine (323 mg, 1.23 mmol), diethylazodicarboxylate (194 μL, 1.23 mmol), and phthalimide (181 mg, 1.23 mmol). The solution is aUowed to stir overnight at room temperature under N 2 . The reaction mixture is concentrated and purified by silica gel chromatography (25 g SG, 20% EtOAc/hexane) to give 518 mg (89%) of the title compound as an off-white, amorphous soUd. IR (mineral oil) 1773, 1754, 1744, 1722, 1713, 1671, 1433, 1398, 1309, 1264, 1164, 1116, 706 cm '1 ; l H NMR (300 MHz, CDClg) δ 7.80-7.90, 7.65-7.80, 7.20-7.35, 4.41, 3.60-3.85, 3.05-3.25, 2.59, 2.30-2.50, 2.00-2.20, 1.75-1.95, 1.40-1.75, 1.48, 0.87; MS (FAB) mlz 519, 464, 463, 445, 417, 230, 91, 57. Step 10. Preparation of α-[2-(l,3-DUιydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-3- pyrroUdineacetamide. A cold (0 °C) solution of tert-butyl α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-3-(2-metnylpropyl)-2-oxo-l-(phenylmethyl)-3-pyrroUdineacetate (500 mg, 0.964 mmol) in CH 2 C1 (2 ml) is treated with TFA (2 mL) and maintained at 0 °C for 1 hour, and then at room temperature for 1 hour. The solvent is removed in vacuo to give a quantitative yield of α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-3-pyrroUdineacetic acid as a gelatinous soUd. IR (Uq.) 2962, 1775, 1755, 1716, 1617, 1469, 1455, 1441, 1402, 1377, 1309, 721, 702 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.80-7.90, 7.70-7.80, 7.10-7.30, 4.44, 3.60-3.90, 3.32, 2.68, 1.80-2.25, 1.55-1.75, 0.91, 0.84; MS (El) mlz 462, 406, 302, 244, 232, 230, 188, 160, 91. A cold (0 °C) solution of α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3- (2-methylpropyl)-2-oxo-l-(phenylmethyl)-3-pyrrolidineacetic acid (559 mg) in Cr^Cl jj /DMF (8 mL 2 L) is treated with 1-hydroxybenzotriazole (158 mg, 1.17 mmol), 4-methylmorphoUne (129 μL, 1.17 mmol), and EDC (224 mg, 1.17 mmol). After 1 hour, additional 4-methylmorpholine (159 μL, 1.45 mmol) and hydroxylamine HCl (101 mg, 1.45 mmol) are added. The solution is aUowed to slowly warm to room temperature, stirring under N 2 overnight. The reaction mixture is diluted with H 2 0 (25 mL) and extracted into CH 2 C1 2 (3 x 50 mL). The organic extracts are dried over anhydrous N^SO^ filtered, concentrated under reduced pressure, and reconstituted in EtOAc (50 mL). The EtOAc layer is washed with more H 2 0 (3 x 25 mL) and brine (25 mL). The organic layer is dried over anhydrous Na 2 S0 , filtered, and concentrated under reduced pressure to give 416 mg of white foam. The foam is purified by silica gel chromatography (50 g SG, 2% MeOH/CHClg) to yield 220 mg of white foam which is triturated with Et 2 0 to give 181 mg (39%) of the title compound as a white soUd (mp 162-164 °C). IR (mineral oU) 3167, 3059, 3033, 3022, 1776, 1710, 1666, 1653, 1498, 1396, 1265, 706, 696 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.80-7.90, 7.65-7.80, 7.05-7.40, 4.20-4.60, 3.60- 4.00, 3.05-3.35, 1.40-2.75, 0.75-0.95; MS (El) mlz 417, 445, 421, 417, 248, 247, 188, 160, 91. EXAMPLE 23 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l- (phenylmethyl)-3-pyrroUdineacetamide. FoUowing the general procedure in EXAMPLE 22 and making non-critical variations but starting with tert-butyl N-tert-butyloxycarbonyl-3-(2-methylpropyl)-2- oxo-3-pyrroUdineacetate (EXAMPLE 22, step 4), the title compound is obtained (mp 119-120 °C). IR (mineral oil) 3265, 3164, 3065, 3029, 3016, 1658, 1519, 1494, 1305, 1291, 1260, 1063, 701, 651, 617 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 10.13, 7.60-8.30, 7.10-7.40, 4.44, 3.10-3.30, 2.48, 2.15-2.30, 1.95-2.10, 1.35-1.85, 0.88, 0.87; MS (El) mlz 304, 272, 248, 215, 188, 187, 186, 92, 91, 65. EXAMPLE 24 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l- (phenylmethyl)-α-[2-(4,5,6,7-tetrafluoro-l,3-dihydro-l,3-dioxo- 2H-isoindol-2-yi)ethyl]-3 -pyrroUdineacetamide . Following the general procedure in EXAMPLE 22 and making non-critical variations but starting with tert-butyl α-(2-hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l- (phenylmethyl)-3-pyrroUdineacetate (EXAMPLE 22, step 8), the title compound is obtained (mp 183-185 °C). IR (mineral oU) 3221, 1724, 1713, 1694, 1672, 1629, 1513, 1503, 1418, 1262, 1155, 1033, 954, 941, 754 cm '1 ; NMR (300 MHz, CDClg) δ 7.10-7.40, 4.25-4.55, 3.60-4.00, 3.10-3.35, 2.40- 2.55, 1.40-1.35, 1.80-1.95; MS (FAB) m/z 550, 534, 517, 489, 230, 91. EXAMPLE 25 Preparation of l-(3-Fluorophenyl)methyl)-α-[2-(l,3-dmydro-l,3- dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2- oxo-3-pyrroUdineacetamide. FoUowing the general procedure in EXAMPLE 22 and making non-critical variations but starting with tert-butyl 3-(2-methylpropyl ) -2-oxo-α-(propen-2-yl)-3- pyrrolidineacetate (EXAMPLE 22, step 6), the title compound is obtained (mp 162- 163 °C). IR (mineral oil) 3169, 3058. 3048, 1776, 1709, 1667, 1653, 1614, 1590, 1487, 1397, 1292, 1267 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.75-7.90, 7.65-7.75, 7.15-7.35, 6.80-7.00, 4.40, 3.60-3.85, 3.10-3.30, 2.30-2.65, 1.40-2.25, 0.85, 0.79; MS (El) mlz 495, 463, 435, 379, 322, 288, 248, 206, 160, 138, 109. EXAMPLE 26 Preparation of α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-l,3- pyrroUdinediacetamide. FoUowing the general procedure in EXAMPLE 22 and making non-critical variations but starting with tert-butyl 3-(2-methylpropyI)-2-oxo-α-(propen-2-yl)-3- pyrroUdineacetate (EXAMPLE 22, step 6), the title compound is obtained (mp 120 °C, dec). IR (mineral oil) 3296, 3100, 3060, 1773, 1714, 1668. 1547, 1496, 1400, 1340, 1299, 1272, 1171, 1038 cm "1 ; NMR (300 MHz, CDClg) δ 7.80-7.90, 7.65-7.80, 6.85, 4.33, 3.60-3.95, 3.25- 3.55, 2.81, 2.65-2.85, 2.20-2.40, 1.70-2.20, 1.15-1.70, 0.75-0.95, 0.81, 0.68; MS (El) mlz 458, 402, 340, 339, 229, 212, 185, 169, 160, 138. EXAMPLE 27 Preparation of N 3 -Hydroxy-N 1 -methyl-3- ( 2-methylpropyl)-2-oxo- α .[2-(4,5,6,7-tetrafluoro-l,3-dUιydro-l,3-dioxo-2H-isoindol-2- yDethyl]- 1,3-pyrroUdinediacetamide . Me Following the general procedure in EXAMPLE 22 and making non-critical variations but starting with tert-butyl 3-(2-methylpropyl)-2-oxo-α-(propen-2-yl)-3- pyrrolidineacetate (EXAMPLE 22, step 6), the title compound is obtained (mp 130 °C, dec). IR (mineral oil) 3293, 1785, 1723, 1668, 1550, 1514, 1500, 1410, 1314, 1273, 1158, 1035, 944, 754 cm '1 ; X H NMR (300 MHz, CDClg) δ 6.55, 4.30, 3.60-4.00, 3.20-3.55, 2.55-2.90, 1.30- 1.40, 1.10-1.30, 0.89, 0.78; MS (El) mlz 530, 498, 474, 411, 232, 212, 180, 169, 154, 152, 138. EXAMPLE 28 Preparation of [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide . Step 1. Resolution of tert-Butyl N-tert-Butyloxycarbonyl-3-(2-methylpropyl)-2- oxo-3-pyrroUdineacetate. A 20 mg/mL solution of racemic tert-butyl N-tert-butyloxycarbonyl-3-(2- methylpropyl)-2-oxo-3-pyrrolidineacetate (EXAMPLE 22, step 4) is made in the mobUe phase, 2% isopropanol in hexane (V/V). AUquots of 53 mL (1.06 g) are injected onto a 5.1x50 cm Chiralcel OD column (Chiral Technologies, Inc., Exton, PA 19341) using a SepTech 140 HPLC (EM Separations, Inc., Wakefield, RI 02880) instrument in the automated peak shaving and recycling mode. The flow rate is 60 mL/min and the monitor is set at 213 nm. After four passes through the column with appropriate peak shaving, both peaks are obtained in nearly 100% yield at >99% ee for the earUer eluting enantiomer (enantiomer 1) and 96.4% ee for the later eluting enantiomer (enantiomer 2). Enantiomeric excess is determined on a 0.46 x 25 cm Chiralcel OD-H column (Chiral Technologies, Inc.) using 5% isopropanol in hexane (V V) at 0.5 mL/min with the monitor set at 210 nm. Enantiomer 1 eluted at 8.8 minutes and enantiomer 2 eluted at 10.2 minutes (α = 1.42). Step 2. Preparation of (S) tert-Butyl 3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetate. A solution of (S)-tert-butyl N-tert-butyloxycarbonyl-3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetate (193 mg, 0.543 mmol), magnesium methoxide (3.0 mL, 6-10 wt. % in MeOH), and MeOH (2.7 mL) is stirred at room temperature for 16 hours. The solution is poured into water (15 mL) and the mixture acidified with acetic acid. The mixture is extracted several times with CH 2 C1 2 , the combined filtrates dried (MgS0 4 ), filtered, and concentrated to give 124 mg (89%) of the title compound as an oil. IR (mineral oil) 3209, 3100, 3001, 1728, 1691, 1496, 1318, 1302, 1281, 1261, 1208, 1163. 1132. 1079, 969 cm '1 ; 1H NMR (300 MHz, CDClg) δ 5.77, 3.25-3.40, 2.49, 2.20-2.40, 2.05-2.20, 1.65- 1.85, 1.35-1.60, 1.44, 1.42, 0.85-1.00; MS (FAB) mlz 256, 201, 200, 182, 154, 57, 41. Step 3. Preparation of Methyl D-PhenyUactate. A mixture of D-phenyUactic acid (4.79 g, 28.8 mmol), iodomethane (1.80 mL, 28.9 mmol), K^COg (4.07 g, mmol), and DMF (80 mL) is stirred for 16 hours at room temperature. The solution is diluted with 500 mL of ether. The mixture washed with water (3 X 150 mL) and brine (150 mL). The organic layer is dried (MgS0 4 ), filtered, and concentrated to give 3.89 g (75%) of the title compound as a white solid. NMR (300 MHz, CDClg) δ 7.15-7.40, 4.40-4.55, 3.78, 3.13, 2.97, 2.68. Step 4. Preparation of the Trifiate of Methyl D-PhenyUactate. Trifluoromethylsulfonic anhydride (1.37 mL, 8.14 mmol) is added to a solution of methyl D-phenyllactate (1.20 g, 6.66 mmol), CC1 4 (8.6 mL), and pyridine (0.70 mL, 8.7 mmol) at 0 °C. The mixture is stirred for 1 hour at 0 C C and then diluted with pentane (35 mL). The mixture is aUowed to warm to room temperature and is filtered. The soUds are washed with pentane (35 L) and the combined filtrates concentrated. Purification by flash chromatography (4:1 hexane:EtOAc) to give 1.39 g (55%) of the title compound as an oil. 1H NMR (300 MHz, CDClg) δ 7.15-7.40, 5.25, 3.84, 3.35, 3.21. Step 5. Preparation of [S-(R*, R*)]N 3 -tert-Butyl-N 1 -methyl-3-(2-methylpropyl)- 2-oxo-α 1 -(phenylmethyl)-l,3-pyrrolidinediacetate. Sodium hydride (21.4 mg, 0.535 mmol, 60% mineral oU dispersion) is added to a solution of (S) tert-butyl 3-(2-methylpropyl)-2-oxo-3-pyrrolidineacetate (124 mg, 0.486 mmol) and THF (1.65 mL) at 0 °C. The solution is stirred for 15 minutes at 0 °C and then a solution of the trifiate (166 mg, 0.532 mmol) in 0.5 mL of pentane is added. The solution is stirred for 2 hours at 0 °C and 1 hour at room temperature. Aqueous workup (EtOAc, MgS0 4 ) and purification (4:1 hexane:EtOAc) provides 88.3 mg (44%) of the title compound as an oil. IR (liq.) 2956, 2933, 1744, 1731, 1693, 1455, 1435, 1393, 1368, 1352, 1269, 1209, 1156, 1155, 700 cm "1 ; NMR (300 MHz, CDClg) δ 7.15-7.35, 5.14, 3.70, 3.20-3.45, 3.00, 1.95-2.10, 2.08, 1.60-1.80, 1.45-1.55, 1.35-1.45, 1.40, 0.89, 0.86; MS (El) mlz 417, 361, 344, 305, 302, 271, 270, 214, 162, 132, 57. Step 6. Preparation of [S-(R*, R*)3 3-(tert-Butylacetoxy)-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-l-pyrrolidineacetic Acid. A mixture of [S-(R*, R*)]-N 3 -tert-butyl-N 1 -methyl-3-(2-methylpropyl)-2-oxo- α 1 -(phenylmethyl)-l,3-pyrrolidinediacetate (254 mg, 0.608 mmol), MeOH (12 mL), water (3.0 mL), and sodium hydroxide (98.4 mg, 2.46 mmol) is stirred at room temperature for 16 hours and then concentrated. The residue is diluted with water, acidified (10% HCl) and the aqueous layer extracted several times with CH^ ^. The organic layers are dried (MgS0 4 ), filtered, and concentrated to give 233 mg (95%) of the title compound as an oil. IR (Uq.) 2958, 2933, 2872, 1730, 1693, 1651, 1456, 1443, 1393, 1368, 1273, 1258, 1207, 1155, 699 cm "1 ; H NMR (300 MHz, CDClg) δ 7.20-7.35, 4.67, 3.40, 3.20-3.35, 3.00-3.10, 2.29, 1.95-2.10, 1.80-1.95, 1.60-1.75, 1.52, 1.41, 1.31, 0.91, 0.87; MS (El) mlz 403, 347, 330, 303, 302, 291, 256, 200, 132, 57, 55. Step 7. [S-(R*, R*)] tert-Butyl N 1 -Methylacetamide-3-(2-methylpropyl)-2-oxo- α 1 -(phenylmethyl)-3-pyrroUdineacetate. CDI (94.3 mg, 0.582 mmol) is added to a solution of [S-(R*, R*)] 3-(tert- butylacetoxy)-3-(2-methylpropyl)-2-oxo-α -(phenylmethyl)-l-pyrroUdineacetic acid (224 mg, 0.555 mmol) and THF (2.5 mL). The solution is stirred for 1 hour at room temperature and then 0.27 mL of 40% aq methylamine is added. The solution is stirred at room temperature for 16 hours. Aqueous workup (EtOAc, 3% HCl, 10% NaOH and brine washes, MgS0 4 ) gives 259 mg of crude product which is purified by flash chromatography (1:1 hexane:EtOAc) to give 198 mg (86%) of the title compound as an oU. IR (mineral oU) 3395, 1719, 1682, 1656, 1545, 1442, 1351, 1306, 1274, 1248, 1210, 1150, 1117, 747, 703 cm "1 ; % NMR (300 MHz, CDClg) δ 7.15-7.30, 6.90-7.05, 4.25, 3.41, 3.20-3.35, 2.95- 3.10, 2.82, 2.43, 1.95-2.10, 1.75-1.90, 1.50-1.70, 1.43, 1.08, 0.88, 0.81; MS (El) mlz 416 (M + ) 360, 358, 343, 303, 302, 284, 269, 161, 132, 57. Step 8. Preparation of [S-(R*, R*)] N 1 -Methylacetamide-3-(2-methylpropyl)-2- oxo-α -(phenylmethyl)-3-p vrroUdineacetic Acid . TFA (3.0 mL) is added to a solution of [S-(R*, R*)] tert-butyl N 1 - methylacetamide-3-(2-methylpropyl)-2-oxo-cc -(phenylmethyl)-3-pyrroUdineacetate (192 mg, 0.461 mmol) and CJL j CL j (3.0 mL) at 0 °C. The solution is stirred for 1 hour at 0 °C and for 3 hours at room temperature. The solution is concentrated which is repeated twice more from CH 2 C1 2 (2 X 30 mL). Aqueous workup (CH 2 C1 2 , MgS0 4 ) provides 158 mg (95%) of the title compound as an oU. 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 6.10-6.25, 4.66, 3.25-3.50, 3.17, 2.76, 2.38, 2.00-2.10, 1.60-1.85, 1.53, 1.25-1.40, 0.90, 0.84; MS (El) mlz 360, 303, 302, 284, 269, 161, 149, 132, 69, 57, 55. Step 9. Preparation of [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)- 2-oxo-α 1 -(phenylmethyl)-l,3-pyrroUdinediacetamide. EDC (92.2 mg, 0.481 mmol) is added to a solution of [S-(R*, R*)] N 1 - methylacetamide-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-3-pyrroUdineacetic acid (151 mg, 0.419 mmol), CH 2 C1 2 (4.1 mL), DMF (1.0 mL), HOBT (56.4 mg, 0.417 mmol), and N-methylmorpholine (50 μL, 0.46 mmol) at 0 °C. The solution is stirred for 5 minutes at 0 °C and 1 hour at room temperature. Hydroxylamine hydrochloride (57.8 mg, 0.832 mmol) and N-methylmorpholine (90 μL, 0.82 mmol) are added and the mixture stirred overnight at room temperature. Aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by flash chromatography (20:1 CH 2 Cl 2 :MeOH) provided 74 mg of the hydroxamate as an oU which is crystallized from ether/EtOAc/hexane to give 50 mg (32%) of the title compound as a white crystalline material (mp 159-164 °C): [α] D 25 -84° (c 0.49, CHClg). IR (mineral oU) 3372, 3196, 3028, 1687, 1669, 1635, 1605, 1543, 1441, 1404, 1355, 1302, 1287, 747, 703 cm "1 ; MS (El) mlz 375, 317, 316, 302, 299, 284, 200, 132, 91, 58, 55. EXAMPLE 29 Preparation of [R,R-(R*, R*)]-α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl]-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)- 1 , 3-pyrroUdinediacetamide. Step 1. Preparation of (R) tert-Butylmethyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)-α 3 -(propen-2-yl)-l,3-pyrroUdinediacetate. Sodium hydride (129 mg, 3.23 mmol, 60% mineral oU dispersion) is added to a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-α-(propen-2-yl)-3-pyrroUdineacetate (EXAMPLE 22, step 6; 862 mg, 2.92 mmol) and THF (10 mL) at 0 °C. The solution is stirred for 20 minutes at 0 °C and then a solution of the trifiate (EXAMPLE 28, step 4; 1.01 g, 3.23 mmol) in 2.0 mL of pentane is added. The solution is stirred for 2 hours at 0 °C and 1.5 hours at room temperature. Aqueous workup (EtOAc, MgS0 4 ) and purification (4:1 hexane:EtOAc) provided 922 mg (69%) of the title compound as an oU which is a mixture of diastereomers. m (Uq.) 2975, 2956, 2934, 1745, 1724, 1690, 1455, 1435, 1425, 1368, 1288, 1267, 1237, 1210, 1153, cm "1 ; 1H NMR (300 MHz, CDClg) major peaks only δ 3.71, 3.70, 1.40, 1.38, 0.89, 0.83, 0.69, 0.56; MS (El) mlz 457, 401, 342, 310, 304, 303, 260, 200, 162, 91, 57. Step 2. Preparation of (R) 3-(tert-Butylacetoxy)-3-(2-methylpropyl)-2-oxo-α 1 -l- (phenylmethyl)-α -(propen-2-yl)- 1-pyrroUdineacetic Acid. A mixture of (R) tert-butylmethyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- α 3 -(propen-2-yl)-l,3-pyrroUdinediacetate (913 mg, 2.00 mmol), MeOH (32 mL), water (8.0 mL), and sodium hydroxide (362 mg, 9.05 mmol) is stirred at room temperature for 16 hours and then concentrated. The residue is diluted with water, acidified (10% HCl), and the aqueous layer extracted several times with CH 2 C1 2 . The organic layers are dried (MgS0 ), filtered, and concentrated to give 829 mg (93%) of the title compound as an oU. IR (liq.) 3003, 2974, 2959, 2932, 1725, 1692, 1652, 1643, 1455, 1368, 1284, 1272, 1255, 1206, 1153 cm "1 ; X H NMR (300 MHz, CDClg) major peaks only δ 3.57, 2.99, 2.69, 1.40, 1.38, 0.89, 0.85, 0.61, 0.59; MS (El) mlz 443, 387, 342, 296, 290, 289, 252, 246, 200, 91, 57. Step 3. Preparation of [R,R-(R*, R*)] and [S,R-(S*, S*)] tert-Butyl N 1 - Methylacetamide-3-(2-methylpropyl)-2-oxo-α 1 -l-(phenylmethyl)-α 3 - (propen-2-yl)-3-pyrrolidineacetate. CDI (314 mg, 1.94 mmol) is added to a solution of (R) 3-rtert-butylacetoxy)-3- (2-methylpropyl)-2-oxo-α 1 -l-(phenylmethyl)-α 3 - ( propen-2-yl)-l-pyrrolidineacetic acid (821 mg, 1.85 mmol) and THF (8.0 mL). The solution is stirred for 1 hour at room temperature and then 1.1 mL of 40% aq methylamine is added. The solution is stirred at room temperature for 16 hours. Aqueous workup (EtOAc, 3% HCl, 10% NaOH and brine washes, MgS0 4 ) gives 921 mg of crude product which is purified by flash chromatography (1:1 hexane:EtOAc) to give 126 mg of diastereomer A. Further elution provided diastereomer B contaminated by diastereomer A and two minor diastereomers. Repurification of the mixture by flash chromatography (two coUums; 1:1 hexane EtOAc) provides an additional 174 mg of diastereomer A (total 300 mg, 36%) as an oU. IR (mineral oil) 3376, 1702, 1685, 1667, 1538, 1501, 1443, 1433, 1277, 1267, 1249, 1232, 1156, 742, 697 cm "1 ; MS (El) mlz 456, 400, 399, 398, 343, 342, 324, 309, 200, 132, 57. Further elution provided 209 mg (25%) of impure diastereomer B: IR (liq.) 3328, 2975, 2957, 2934, 1724, 1663, 1554, 1498, 1455, 1438, 1368, 1292, 1266, 1152, 699 cm "1 ; X rl NMR (300 MHz, CDClg) δ 7.10-7.30, 6.25-6.35, 5.50-5.70, 4.90-5.10, 4.64, 3.30-3.45, 3.08, 2.80, 2.71, 2.10-2.40, 1.70-1.90, 1.30-1.65, 0.86, 0.79; MS (El) mlz 456, 400, 398, 343, 342, 324, 309, 259, 200, 132, 57. Step 4. Preparation of [R,R-(R*, R*)]-tert-Butyl α 3 -(2-Hydroxyethyl)-N 1 - methylacetamide-3-(2-methylpropyl)-2-oxo-α -l-(phenylmethyl)-3- pyrrolidineacetate. Ozone is passed through a solution of [R,R-(R*, R*)]-tert-butyl N 1 - methylacetamide-3-(2-methylpropyl)-2-oxo-α -(phenylmethyl)-α °-(propen-2-yl)-3- pyrroUdineacetate (EXAMPLE 29, step 3, diastereomer B; 203 mg, 0.445 mmol) and EtOH (4.4 mL) at -78 °C for 4 minutes. After purging with oxygen, sodium borohydride (27 mg, 0.71 mmol) is added. The mixture is stirred at -78 °C for 1 hour and then aUowed to slowly warm to room temperature over 1 hour. After 1 hour at room temperature, sodium borohydride (14 mg, 0.37 mmol) is added and the mixture stirred an additional 2 hours at room temperature. Concentration and aqueous workup (EtOAc, MgSO 4 ) provided 198 mg (97%) of the title compound as an oU which is carried on crude. IR (liq.) 3320, 2957, 2934, 1722, 1659, 1455, 1437, 1414, 1392, 1368, 1260, 1152, 1057, 734, 699 cm "1 ; l H NMR (300 MHz, CDC1 3 ) δ 7.10-7.35, 6.15-6.25, 4.64, 2.70, 1.44, 0.86, 0.79; MS (El) mlz 460, 346, 328, 132, 105, 91, 81, 69, 58, 57, 55. Step 5. Preparation of [R,R-(R*, R*)]-tert-Butyl α 3 -[2-(l,3-Dilιydro-l,3-dioxo- 2H-isoindol-2-yl)ethyl]-N 1 -methylacetamide-3-(2-methylpropyl)-2-oxo- α 1 -l-(phenylmethyl)-3-pyrrolidineacetate. DEAD (73.4 uL, 0.446 mmol) is added to a solution of [R,R-(R*, R*)]-tert-butyl α 3 -(2-hydroxyethyl)-N 1 -methylacetamide-3-(2-methylpropyl)-2-oxo-α 1 -l- (phenylmethyl)-3-pyrroUdineacetate (195 mg, 0.423 mmol), triphenylphosphine (122 mg, 0.465 mmol), phthaUmide (68.1 mg, 0.463 mmol) and THF (5.0 mL). The solution is stirred for 16 hours at room temperature. Concentration and purification by flash chromatography (two coUums; 1:1 hexane:EtOAc) give 144 mg (58%) of the title compound as an oil. 2 H NMR (300 MHz, CDC1 3 ) major peaks δ 7.78-7.90, 7.65-7.75, 7.10-7.35, 6.30-6.40, 4.59, 2.71, 1.49, 0.83, 0.78. Step 6. Preparation of [R,R-(R*, R*)]-α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol- 2-yl)ethyl]-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -l- (phenylmethyl)-l,3-pyrroUdinediacetamide. TFA (2.0 mL) is added to a solution of [R,R-(R*, R*)]-tert-butyl α 3 -[2-(l,3- dihydro- 1 , 3-dioxo-2H-isoindol-2-yl)ethyl]-N 1 -methylacetamide-3-( 2-methylpropyl)-2- oxo-α -l-(phenylmethyl)-3-pyrroUdineacetate (144 mg, 0.244 mmol) and CH 2 C1 2 (2.0 mL) at 0 °C. The solution is stirred for 0.5 hours at 0 °C and for 1.5 hours at room temperature. The solution is concentrated which is repeated twice more from CH 2 C1 2 (2 X 40 mL). Aqueous workup (CH 2 C1 2 , MgS0 4 ) provides 127 mg (97%) of the acid intemediate as an oU. EDC (52.7 mg, 0.275 mmol) is added to a solution of the crude acid (127 mg, 0.238 mmol), CH 2 C1 2 (2.4 mL), DMF (0.6 mL), HOBT (32.2 mg, 0.238 mmol), and N- methylmorpholine (28.5 μL, 0.259 mmol) at 0 °C. The solution is stirred for 5 minutes at 0 °C and 1 hour at room temperature. Hydroxylamine hydrochloride (33.2 mg, 0.478 mmol) and N-methylmorpholine (51 μL, 0.46 mmol) are added and the mixture stirred overnight at room temperature. Aqueous workup (CΗ CL,, MgS0 4 ) and purification by flash chromatography (40:1 EtOAc.MeOH) provides 65.9 mg of the title compound as an oil which is crystalUzed from ether/hexane to give 45 mg (34%) of the product as a white powder material (mp 176-180°C ). IR (mineral oU) 1714, 1672, 1634, 1401 cm '1 ; NMR (300 MHz, CDC1 3 ) δ 7.70-7.90, 7.05-7.35, 6.85-7.00, 6.10-6.20, 4.68, 3.35-3.75, 3.41, 3.23, 2.90-3.10, 2.70, 2.32, 2.10-2.35, 1.30-1.95, 0.82, 0.73; MS (El) mlz 548, 430, 429, 302, 259, 244, 200, 185, 160, 130, 56. EXAMPLE 30 Preparation of [S-(R* , R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide . Step 1. Preparation of (γS)-α-(2-Methylpropen-2-yl)-γ-trityloxymethyl-γ- butyrolactone. Lithium diisopropylamide (10.6 mL, 21.2 mmol, 2.0 M, heptane/THF/ethylbenzene) is added to a solution of S-(+)-γ-trityloxymethyl-γ- butyrolactone (6.36 g, 17.6 mmol), THF (51 mL), and HMPA (3.8 mL) at -78 °C. After stirring for 30 minutes at -78 °C, a solution of 3-bromo-2-methyipropene (1.96 mL, 19.4 mmol) and THF (10.0 mL) is added. The solution is aUowed to stir for 4 hours at -78 °C and is then quenched with aqueous ammonium chloride (50 mL). After warming to room temperature, aqueous workup (EtOAc, MgS0 4 ) provides an oU which is crystalUzed from hexane/EtOAc (4:1) to give 3.89 g of the title compound as a white soUd (mp 134-135.5°C). The filtrate is concentrated and purified by flash chromatography (4:1 hexane:EtOAc) to give additional title compound (6.11 g total, 84%): IR (mineral oil) 1764, 1489, 1216, 1179, 1151, 1102, 1041, 1029, 962, 902, 771, 749, 707, 694, 636 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.15-7.50, 4.81, 4.72, 4.50-4.65, 3.45, 3.13, 2.95- 3.15, 2.60-2.70, 1.85-2.25, 1.73; MS (El) mlz 412, 335, 259, 258, 244, 243, 165, 105, 93, 77, 55. Step 2. Preparation of (γS)-α-(2-Methylpropyl)-γ-trityloxymethyl-γ- butyrolactone. A mixture of (γS)-α-(2-methylpropen-2-yl)-y-trityloxymethyl-γ-butyrolactone (6.10 g, 14.8 mmol), 10% Pd/C (800 mg) and EtOAc (250 mL) is hydrogenated (42 psi) in a Parr flask at room temperature for 18 hours. The mixture is filtered and the residue washed with EtOAc, CH 2 C1 2 , and EtOAc. The filtrate is dried (MgS0 4 ), filtered, and concentrated to give 5.67 g (92%) of the title compound as an oU which is a mixture of diastereomers. IR (liq.) 2956, 2930, 2871, 1773, 1490, 1449, 1227, 1172, 1093, 1033, 974, 767, 747, 706, 633 cm "1 ; NMR (300 MHz, CDClg) δ 7.15-7.50, 4.50-4.65, 3.44, 3.12, 2.80-2.95, 2.15- 2.30, 1.85-2.00, 1.60-1.85, 1.20-1.40, 0.95, 0.91; MS (El) m z 414, 337, 259, 258, 244, 243, 165, 109, 105, 77, 69. Step 3. Preparation of [S-(R*, R*)]-α-(2-Methylpropyl)-α-(propen-2-yl)-γ- trityloxymethyl-γ-butyrolactone. Lithium diisopropylamide (8.3 mL, 16.6 mmol, 2.0 M, heptane/THF/ethylbenzene) is added to a solution of (τS)-α-(2-methylpropyl)-γ- trityloxymethyl-γ-butyrolactone (5.67 g, 13.7 mmol), THF (50 mL), and HMPA (2.9 mL) at -78 °C. After stirring for 30 minutes at -78 °C, a solution of aUyl bromide (1.46 mL, 16.9 mmol) and THF (8.0 mL) is added. The solution is aUowed to stir for 4 hours at -78 °C and is then quenched with aqueous ammonium chloride (50 mL). After warming to room temperature, aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (6:1 hexane:EtOAc) to give 5.12 g of the title compound (82%) as a white powder (mp 84-85 °C). IR (mineral oil) 1770, 1489, 1184, 1119, 1089, 1070, 1034, 1027, 1002, 991, 775, 754, 704, 632 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.50, 5.65-5.85, 5.10-5.20, 4.40-4.55, 3.15- 3.35, 2.20-2.40, 1.90-2.15, 1.45-1.80, 0.92, 0.85; MS (El) m/z 454, 377, 259, 258, 244, 243, 165, 109, 105, 77, 55. Step 4. Preparation of [S-(R*, R*)]-α-(2-Methylρropyl)-α-(propen-2-yl)-γ- hydroxymethyl-γ-butyrolactone. TFA (15.0 mL) is added to a solution of [S-(R*, R*)]-α-(2-methylpropyl)-α- (propen-2-yl)-γ-trityloxymethyl-γ-butyrolactone (2.09 g, 4.60 mmol) and CH 2 C1 2 (30.0 mL) at 0 °C. The solution is stirred for 75 minutes at 0 °C and is concentrated. Aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by flash chromatography (1:1 hexane:EtOAc) provides 684 mg (70%) of the title compound as an oil. IR (liq.) 3434, 2958, 2932, 2872, 1767, 1368, 1191, 1140, 1101, 1075, 1058, 1034, 998, 923, 622 cm '1 ; 1H NMR (300 MHz, CDClg) δ 5.70-5.90, 5.10-5.25, 4.45-4.55, 3.89, 3.60, 2.00- 2.50, 1.60-1.90, 1.52, 0.96, 0.89; MS (El ) m/z 212, 156, 111, 109, 93, 81, 69, 67, 55, 43, 41. Step 5. Preparation of [R*,R*] α-(2-Methylpropyl)-α-(propen-2-yl)-γ-hydroxy-γ- butyrolactone. A mixture of [S-(R*, R*)]-α-(2-methylpropyl)-α-(propen-2-yl)-γ-hydroxymethyl- γ-butyrolactone (682 mg, 3.21 mmol), NaOH (350 mg, 8.75 mmol), THF (40 mL), and H 2 0 (10 mL) is stirred for 19 hours at room temperature. Additional NaOH (114 mg, 2.85 mmol) is added after 16 hours. The mixture is concentrated and the residue taken up into MeOH (43 mL). A solution of sodium periodate (862 mg, 4.03 mmol) and H 2 0 (4.3 mL) is added and the mixture stirred at room temperature for 3 hours. After concentration, the aqueous residue is acidified (HCl) and extracted with CH 2 C1 2 (3 X 40 mL). The organic layers are dried (MgS0 4 ), filtered, and concentrated to provide 625 mg (98%) of the title compound as a semi-solid. IR (liq.) 3389, 2959, 2933, 2873, 1769, 1747, 1746, 1369, 1186, 1170, 1129, 988, 963, 944, 926 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 5.60-5.90, 5.10-5.25, 3.30-3.50, 1.45-2.55, 0.85- 1.00; MS (El ) m/z 142, 113, 97, 95, 67, 57, 55, 43, 41, 39. Step 6. Preparation of L-Phenylalanine Methyl Amide. CDI (545 mg, 3.36 mmol) is added to a solution of CBZ-L-phenylalanine (1.00 g, 3.34 mmol) and THF (12.5 mL). The solution is stirred for 1 hour at room temperature and then 40% aqueous methylamine (1.5 mL) is added. The solution is stirred for 16 hours at room temperature. The solution is diluted with EtOAc and is washed with NaHC0 3 , 10% HCl, NaHCOg, and brine. The organic layer is dried (MgS0 4 ), filtered, and concentrated to give 983 mg (94%) of the carbamate intermediate as a white soUd. X H NMR (300 MHz, CDClg) δ 7.10-7.40, 5.50-5.65, 5.25-5.40, 5.07, 4.33, 2.95- 3.20, 2.70. Ammonium formate (644 mg, 10.2 mmol) is added to a mixture of the carbamate (980 mg, 3.14 mmol), MeOH (21 mL), and 10% Pd C (104 mg). The mixture is stirred for 1 hour at room temperature and is filtered. The residue is washed with MeOH, CH 2 C1 2 , and is concentrated. The residue is diluted with 30:1 CH 2 Cl 2 :MeOH (30 mL), dried (MgS0 4 ), filtered, and concentrated to provide 504 mg (90%) of the title compound as a foam which is carried on crude. NMR (300 MHz, CDClg) δ 8.12, 7.15-7.40, 4.07, 3.72, 3.26, 2.65-2.85, 2.78. Step 7. Preparation of [S-(R*, R*)] Methyl-3-(2-methylpropyl)-2-oxo-α- (phenylmethyl)-3-(propen-2-yl)-l-pyrroUdineacetamide. A solution of L-phenylalanine methyl amide (EXAMPLE 30, step 6; 210 mg, 1.18 mmol) and MeOH (8.5 mL) is added to [R*,R*] α-(2-methylpropyl)-α-(propen-2- yl)-γ-hydroxy-γ-butyrolactone (EXAMPLE 30, step 5; 200 mg, 1.01 mmol). Sodium cyanoborohydride (85.0 mg, 1.35 mmol) is added and the solution stirred for 16 hours at room temperature. Concentration and aqueous workup (20:1 CHCl 3 :MeOH, MgS0 4 ) provided 397 mg of the uncycUzed intermediate as an oU. A mixture of the crude residue, toluene (24 mL), MeOH (8.0 mL), and siUca gel (800 mg) is slowly heated to reflux aUowing the MeOH to boU off. The mixture is then maintained at reflux for 3 hours and is aUowed to cool to room temperature. The mixture is filtered, the soUds washed with 20:1 CH 2 Cl 2 :MeOH (3 X 40 mL), and the filtrate concentrated. Purification by flash chromatography (EtOAc) provided 218 mg (63%) of the title compound as an oU. IR (liq.) 3314, 2955, 2929, 2871, 1661, 1660, 1558, 1498, 1455, 1439, 1413, 1296, 1267, 741, 698 cm "1 ; NMR (300 MHz, CDClg) δ 7.15-7.35, 6.15-6.30, 5.10-5.35, 4.75-5.00, 3.15- 3.40, 3.07, 2.74, 2.00-2.15, 1.55-2.00, 1.35-1.55, 0.90, 0.81; MS (El) m/z 342, 311, 299, 285, 284, 162,132, 105, 91, 81, 67, 58, 55. Step 8. Preparation of [S-(R*, R*)] N 1 -Methylacetamide-3-(2-methylpropyl)-2- oxo-α -(phenylmethyl)-3-pyrroUdineacetic Acid. Ruthenium(IV) oxide hydrate (17.3 mg, 0.130 mmol) is added to a mixture of sodium periodate (1.07 g, 5.00 mmol), H 2 0 (14.0 mL), CHgCN (14.0 mL), and CC1 4 (14.0 mL). The mixture is stirred for 20 minutes at room temperature and then NaHCOg (1.32 g, 15.7 mmol) and H 2 0 (7.0 mL) are added. After stirring an additional 5 minutes, a solution of [S-(R*, R*)]-methyl-3-(2-methylpropyl)-2-oxo-α- (phenylmethyl)-3-(propen-2-yl)-l-pyrroUdineacetamide (215 mg, 0.628 mmol) and CHgCN (6.0 mL) is added. After stirring for 8 minutes at room temperature, the residue is poured into a mixture of H 2 0 (40 mL) and EtOAc (100 mL). The aqueous layer is removed and the organic layer extracted with 10% NaOH (2 X 15 mL). The combined basic layers are acidified (4 N HCl) and extracted with CH 2 C1 2 (3 X 50 mL). The CH j CL) layers are dried (MgS0 4 ), filtered, and concentrated to provide 109 mg (48%) of the title compound as an oil. IR (Uq.) 3347, 3029, 2957, 2872, 1724, 1657, 1552, 1498, 1455, 1440, 1413, 1296, 1271, 1193, 700 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.10-7.40, 6.81, 4.54, 3.15-3.50, 2.73, 2.45, 1.80- 2.05, 1.55-1.75, 1.40-1.55, 1.24, 0.89, 0.82; MS (El) mlz 360, 303, 302, 284, 269, 244, 200, 161, 132, 91, 55. Step 9. Preparation of [S-(R*, R*)]-N 3 -Benzyloxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-α -(phenylmethyl)- 1 , 3-pyrroUdinediacetamide. CDI (59.0 mg, 0.364 mmol) is added to a solution of [S-(R*, R*)] N 1 - methylacetarmde-3-(2-metnylpropyl)-2-oxo-α 1 (phenylmethyl)-3-pyrroUdineacetic acid (109 mg, 0.302 mmol) and CH 2 C1 2 (2.3 mL). The solution is stirred for 1 hour at room temperature and then 0-benzylhydroxylamine hydrochloride (70.0 mg, 0.439 mmol) and N-methylmorpholine (0.06 mL, 5.5 mmol) are added. The solution is stirred for 16 hours at room temperature. Aqueous workup (CP^Cl^ MgS0 4 ) and purification by flash chromatography (EtOAc) provides 82.4 mg (59%) of the title compound as an oU. IR (liq.) 3213, 3031, 2957, 2872, 1662, 1545, 1498, 1455, 1441. 1412, 1368, 1295, 1280, 750, 699 cm "1 ; l H NMR (300 MHz, CDClg) δ 8.85-9.00, 7.10-7.50, 6.40-6.55, 4.75-5.00, 4.40- 4.55, 3.10-3.45, 2.75, 2.15-2.30, 1.80-2.15, 1.40-1.65, 1.10-1.30, 0.87, 0.79; MS (El) m/z 465, 407, 284, 132, 105, 92, 91, 77, 69, 58, 55. Step 10. Preparation of [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)- 2-oxo-α ^(phenylmethyl)- 1 ,3-pyrroUdinediacetamide. An atmosphere of hydrogen is placed over a mixture of [S-(R*, R*)]-N 3 - benzyloxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide (79.2 mg, 0.170 mmol), MeOH (4.0 mL) and 10% Pd C (15 mg). After stirring for 4 hours at room temperature, the mixture is filtered, the soUds washed with MeOH (4 X 5 mL) and CH 2 C1 2 (5 mL), and the combined filtrate concentrated to provide 41 mg of the desired product as an oU. Trituration (etherhexane) provides 39.4 mg (62%) of the title compound as a white powder (mp 162-165°C): [α] D 25 -96° (c 0.26, CHC1 3 ). IR (mineral oU) 3372, 3195, 3028, 1687, 1669, 1636, 1605, 1542, 1441, 1405, 1355, 1302, 1287, 747, 704 cm '1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.40, 6.50-6.65, 4.50-4.65, 3.10-3.50, 2.78, 2.32, 1.90-2.15, 1.45-1.80, 1.20-1.35, 0.90, 0.83; MS (El) m z 375, 317, 302, 301, 299, 284, 244, 200, 132, 91, 55. EXAMPLE 31 Preparation of [S-(R*. R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-N 1 -(2-phenethyl)-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide. FoUowing the general procedure of EXAMPLE 30 and making non-critical variations but starting with [R*,R*] α-(2-methylpropyl)-α-(propen-2-yl)-γ-hydroxy-γ- butyrolactone (EXAMPLE 30, Step 5) and L-phenylalanine phenethyl amide (prepared siπύlarly to that described in EXAMPLE 30, Step 6), the title compound is obtained (mp 158-159°C). [α] D 25 -83° (c 0.35, CHC1 3 ); IR (mineral oil) 3219, 3087, 3063, 3029, 1668, 1644, 1558, 1498, 1354, 1311, 1297, 1283, 749, 743, 701 cm '1 ; 1H NMR (300 MHz, CDC1 3 ) δ 9.63, 7.00-7.40, 6.31, 4.59, 3.30-3.60, 3.00-3.20, 2.65-2.85, 2.14, 1.85-2.10, 1.40-1.75, 1.25, 0.87, 0.80; MS (El) mlz 465, 318, 317, 316, 284, 200, 132, 105, 91, 55. EXAMPLE 32 Preparation of [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-α 1 ,3-bis (2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. FoUowing the general procedure of EXAMPLE 30 and making non-critical variations but starting with [R*,R*] α-(2-methylpropyl)-α-(propen-2-yl)-γ-hydroxy-γ- butyrolactone (EXAMPLE 30, Step 5) and L-leucine methyl amide (prepared siπύlarly to that described in EXAMPLE 30, Step 6), the title compound is obtained (mp 138-139°C). [α] D 25 +117° (c 0.28, CHClg); IR (mineral oil) 3376, 3198, 3023, 1689, 1676, 1639, 1543, 1493, 1406, 1355, 1304, 1281, 1195, 1166 cm '1 ; 1H NMR (300 MHz, CDClg) δ 9.91, 6.31, 4.35-4.50, 3.30-3.55, 2.76, 2.44, 2.20- 2.40, 2.00-2.15, 1.35-1.90, 0.75-1.00; MS (El) mlz 341, 310, 284, 283, 282, 251, 250, 222, 98, 86, 55. EXAMPLE 33 Preparation of [S-(R*, R*)]-α 1 -(Cyclohexylmethyl)-N 3 -hydroxy- N 1 -methyl-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. FoUowing the general procedure of EXAMPLE 30 and making non-critical variations but starting with [R*,R*] α-(2-methylpropyl)-α-(propen-2-yl)-γ-hydroxy-γ- butyrolactone (EXAMPLE 30, Step 5) and β-cyclohexyl-L-alanine methyl amide (prepared similarly to that described in EXAMPLE 30 Step 6), the title compound is obtained (mp 150-152 °C). IR (mineral oU) 3253, 3194, 3058, 1678, 1643, 1544, 1502, 1409, 1285, 1268, 1259, 1228, 1048, 738, 647 cm '1 ; 1H NMR (300 MHz, CDClg) δ 6.52, 4.42, 3.30-3.55, 2.77, 2.44, 2.20-2.35, 1.95- 2.15, 1.98, 1.35-1.90, 0.75-1.35, 0.92, 0.86; MS (El) mlz 381, 324, 323, 322, 290, 208, 86, 67. EXAMPLE 34 Preparation of [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(3- methylbutyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide. Following the general procedure of EXAMPLE 30 and making non-critical variations but starting with [R*,R*] α-(3-methylbutyl)-α-(propen-2-yl)-γ-hydroxy-γ- butyrolactone (prepared siπύlarly to that described in EXAMPLE 30, Steps 1-5) and L-phenylalanine methyl amide (EXAMPLE 30, step 6), the title compound is obtained (mp 167-168°C). tα] 25 D -104° (c 0.43, CHClg); IR (mineral oil) 3372, 3195, 3064, 3029, 1687, 1670, 1635, 1545, 1497, 1443, 1405, 1297, 1287, 745, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 9.50-9.80, 7.10-7.40, 6.92, 4.40-4.50, 3.10-3.45, 2.79, 2.23, 1.90-2.20, 1.70-1.90, 1.05-1.55, 0.75-1.00; MS (FAB) m z 390, 389, 374, 357, 331, 298, 132. EXAMPLE 35 Preparation of N-Hydroxy-3-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. Step 1. Preparation of Ethyl 3-(2-Methylproρyl)-2,5-dioxo-l-(2-phenylethyl)-3- pyrroUdineacetate. Ruthenium(lV) oxide hydrate (27 mg, 0.20 mmol) is added to a mixture of ethyl 3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrrolidineacetate (prepared similarly to that described in EXAMPLE 1, steps 1-3; 900 mg, 2.71 mmol), sodium periodate (2.71 g, 12.7 mmol), water (27 mL), and CC1 4 (27 mL) at room temperature. After stirring overnight at room temperature, aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by column chromatography (20% EtOAc/hexane) gives 611 mg of the title compound (65%) as a colorless oil. IR (liq.) 2959, 1775, 1733, 1704, 1455, 1438, 1403, 1368, 1346, 1255, 1218, 1193, 1165, 1030, 699 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.15-7.35, 4.09, 3.65-3.85, 2.50-3.00, 1.35-1.80, 1.22, 0.91, 0.85; MS (El) mlz 345, 300, 289, 259, 203, 105, 104. Step 2. Preparation of 3-(2-Methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-3- pyrroUdineacetic Acid. Sodium hydroxide (283 mg, 7.08 mmol) is added to a mixture of ethyl 3-(2- methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-3-pyrroUdineacetate (611 mg, 1.77 mmol), methanol (10 mL), and water (5 mL), and the mixture is aUowed to stir overnight at room temperature. The mixture is partitioned with 10 ml of water and 10 mL of Et^O. The layers are separated and the pH of the aqueous layer was adjusted to pH 2 (pH meter) with 1.2 N HCl. The aqueous layer is extracted with EtOAc (2 x 10 mL) and CH 2 C1 2 (2 x 10 mL), and the combined organic layers are dried (MgS0 4 ), filtered and concentrated to give 500 mg (89%) of the title compound as a white foam which is carried on crude. 1H NMR (300 MHz, CDClg) δ 7.10-7.40, 3.30-3.85, 2.50-2.95, 1.10-1.85, 0.75- 1.00. Step 3. Preparation of N-Benzyloxy-3-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-3-pyrτOUdineacetamide. CDI (153 mg, 0.945 mmol) is added to a mixture of 3-(2-methylpropyl)-2,5- dioxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid (300 g, 0.945 mmol) and CH 2 C1 2 (7.5 mL) at room temperature. After stirring at room temperature for 1 hour, O- benzylhydroxylamine hydrochloride (181 mg, 1.13 mmol) and 4-methylmorpholine (124 μL, 1.13 mmol) are added to the solution. The mixture is aUowed to stir overnight at room temperature. Basic workup (CH 2 C1 2 , NaHCOg, MgS0 4 ) and purification by column chromatography (1.5% MeOH/CHCl 3 ) affordes 70 mg (18%) of the title compound as a white soUd (mp 115-117 °C). (mineral oil) 3195, 1705, 1677, 1659, 1409, 1357, 1182, 1169, 1018, 773, 752, 707, 700, 693, 627 cm '1 ; X H NMR (300 MHz, CDClg) δ 8.53, 8.10-8.30, 7.10-7.45, 4.70-4.90, 3.60-3.80, 2.65-2.95, 2.10-2.65, 1.25-1.60, 0.86, 0.79; MS (El) m/z 422, 389, 366, 300, 260, 229, 194, 179, 125, 105, 104, 91. Step 4. Preparation of N-Hydroxy-3-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. A mixture of N-benzyloxy-3-(2-methylpropyI)-2,5-dioxo-l-(2-phenylethyl)-3- pyrroUdineacetamide (80 mg, 0.19 mmol), Pd C (10%, 5 mg), ammonium formate (59 mg, 0.95 mmol) and EtOH (2.5 mL) is stirred at room temperature. After 2 hours, a second portion of ammonium formate (35 mg, 0.56 mmol) is added and the mixture is allowed to stir overnight at room temperature. The mixture is filtered, and the filter cake washed with MeOH (3 x 15 mL) and CHC1 3 (3 x 15 mL). The filtrate is concentrated, reconstituted in 100 mL of 5%MeOH/CHCl 3 , dried (MgS0 4 ), filtered and concentrated to an oU. CrystaUization from CH Cl 2 Et 2 0/hexane gives 19 mg (31%) of the title compound as a white soUd (mp 136-137 °C). IR (mineral oil) 3316, 3087, 3065, 3027, 1702, 1634, 1563, 1498, 1420, 1229, 1213, 1164, 1083, 1048, 698 cm '1 ; 1H NMR (300 MHz, CDClg) δ 7.10-7.40, 5.63, 3.50, 2.65-2.90, 2.71, 2.54, 1.45- 1.90, 0.92, 0.87; MS (El) mlz 332, 300, 276, 259, 241, 212, 196, 184, 142, 109, 105, 104, 103, 91. EXAMPLE 36 Preparation of N-Hydroxy-3-methyl-4-(2-methylpropyl)-2,5- dioxo-l-(2-phenylethyl)-4-imidazoUdineacetamide. Step 1. Preparation of 3-Methyl-l-(2-phenylethyl)hydantoin. Sodium hydride (921 mg, 23.0 mmol, 60% mineral oil dispersion) is added to a solution of 1-methylhydantoin (2.19 g, 19.2 mmol) and DMF (40 mL) at 0 °C. The mixture was stirred for 1 hour and then (2-bromoethyl)benzene (3.14 mL, 23.0 mmol) is added. The mixture is stirred at 0 °C for 1 hour and 16 hours at room temperature. Aqueous workup (EtOAc, MgS0 4 ) and trituration with ether provides 2.21 g (53%) of the title compound as a white soUd (mp 113-114 °C). IR (mineral oil) 1768, 1758, 1748, 1713, 1488, 1441, 1403, 1340, 1290, 1243, 1134, 995, 989, 748, 704 cm "1 ; l K NMR (300 MHz, CDC1 3 ) δ 7.15-7.35, 3.82, 3.70-3.80, 2.99, 2.85-3.00; MS (El) m/z 218, 105, 104, 99, 91, 78, 65, 57, 56, 51. Step 2. Preparation of 3-Methyl-4-(2-methylpropyl)-l-(2- phenylethyDhydantoin. Lithium dϋsopropylamide (3.45 mL, 6.90 mmol. 2.0 M, heptane/THF/ethylbenzene) is added to a mixture of 3-methyl-l-(2- phenylethyDhydantoin (1.50 g, 6.87 mmol) and THF (27 mL) at -78 °C. After stirring for 30 minutes at -78 °C, l-iodo-2-methylpropane (0.93 mL, 8.08 mmol) is added. The mixture is stirred at -78 C C for 30 minutes and is aUowed to graduaUy warm to room temperature. After stirring at room temperature for 1 hour, aqueous workup (EtOAc, MgS0 ) and purification by flash chromatography (1:1 hexane:EtOAc) gives 467 mg of the title compound (25%) as an oU. Further elution provides 704 mg of recovered starting material (47% of product based on recovered starting material). Spectral data for the title compound. IR (liq.) 2958, 2936, 2871, 1771, 1712, 1498, 1454, 1429, 1412, 1389, 1368, 1142, 1030, 753, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.65-3.85, 2.85-3.00, 2.93, 1.50-1.90, 0.91; MS (El) mlz 274, 218, 127, 114, 105, 104, 91, 43, 41. Step 3. Preparation of 3-Methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)- 4-imidazolidineacetic Acid. Lithium diisopropylamide (0.84 mL, 1.7 mmol, 2.0 M, heptane/THF/ethylbenzene) is added to a solution of 3-methyl-4-(2-methylpropyl)-l- (2-phenylethyl)hydantoin (464 mg, 1.69 mmol) and THF (7.0 mL) at -78 °C. After stirring the partial solution for 30 minutes at -78 °C, ethyl bromoacetate (0.23 mL, 2.1 mmol) is added. The mixture is stirred for 1 hour at -78 °C and is then aUowed to warm to room temperature. After stirring at room temperature for 1 hour, aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (3:1 hexane:EtOAc) gives 407 mg of a 1.25:1 mixture of starting material and the ester intermediate. The mixture could not be purified by chromatography and is carried on crude. Key spectral features for the ester intermediate: H NMR (300 MHz, CDClg) δ 4.00-4.15, 2.84, 1.19, 0.81. A mixture of the crude ester (407 mg), MeOH (12 mL), H 2 0 (2.5 mL) and NaOH (213 mg, 5.33 mmol) is stirred at room temperature for 16 hours and is concentrated. The residue is partitioned between EtOAc and 10% NaOH. The organic layer is dried (MgS0 ), filtered, and concentrated to give 250 mg of starting material. The basic layer is acidified (10% HCl) and extracted several times with CH 2 C1 2 . The CH 2 C-2 layers are dried (MgS0 4 ), filtered, and concentrated to give 117 mg (21%, 45% based on recovered starting material) of the title compound as a white soUd (mp 64-67 °C). IR (mineral oil) 3505, 3374, 1761, 1699, 1499, 1414, 1404, 1336, 1325, 1230, 1136, 1036, 1031, 736, 697 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.70-3.80, 2.80-3.00, 2.85, 2.78, 1.73, 1.55, 1.20-1.40, 0.84, 0.78; MS (El) mlz 332, 276, 275, 273, 241, 231, 105, 104, 91, 56. Step 4. Preparation of N-Benzyloxy-3-methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-4-imidazoUdineacetamide. CDI (57.0 mg, 0.352 mmol) is added to a solution of 3-methyl-4-(2- methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4-imidazoUdineacetic acid (113 mg, 0.340 mmol) and CH 2 C1 2 (2.5 mL). The solution is stirred for 1 hour at room temperature and then O-benzyl hydroxylaminehydrochloride (67.0 mg, 0.420 mmol) and N- methylmorphoUne (46 μL, 0.42 mmol) are added. The solution is stirred for 60 hours at room temperature. Basic workup (CH 2 C1 2 , NaHC0 3 , MgS0 4 ) and purification by flash chromatography (1:1 hexane:EtOAc) provides 94.8 mg (64%) of the title compound as a white soUd. IR (mineral oU) 3198, 3012, 1771, 1713, 1681, 1653, 1522, 1498, 1432, 1414, 1394, 1359, 758, 738, 696 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 8.35-8.55, 7.15-7.50, 4.70-4.90, 3.74, 2.96, 2.84, 2.60-2.90, 2.38, 1.69, 1.45-1.65, 1.20-1.40, 0.80, 0.65-0.85; MS (El) mlz 437, 363, 273, 231, 169, 105, 104, 92, 91, 56. Step 5. Preparation of N-Hydroxy-3-methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-4-imidazoUdineacetamide. Ammonium formate (59.0 mg, 0.936 mmol) is added to a mixture of N- benzyloxy-3-methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazoUdineacetamide (91.0 mg, 0.208 mmol), EtOH (2.5 mL), and 10% Pd/C (15 mg). The mixture is stirred at room temperature for 5.5 hours. Additional ammonium formate (35.0 mg, 0.555 mmol) is added after 2.5 hours. The mixture is filtered, the soUds washed with MeOH (3 X 15 mL) and CHC1 3 (3 X 15 mL), and the filtrate concentrated. The residue was taken up into CHC1 3 (40 mL), dried (MgS0 4 ), filtered, and concentrated to give 64.7 mg (90%) of the title compound as an oU. CrystaUization from ether/hexane provided 46.4 mg (64%) of the title compound as a white powder (mp 127-129 °C). IR (mineral oil) 3223, 3025, 1771, 1701, 1690, 1661, 1497, 1416, 1394, 1359, 1136, 1027, 742, 737, 698 cm "1 ; X H NMR (300 MHz, CDClg) 8 9.55, 7.10-7.30, 3.60-3.85, 2.92, 2.81, 2.55, 1.45- 1.75, 1.15-1.35, 0.76, 0.73; MS (El) mlz 347, 274, 273, 231, 169, 105, 104, 56. EXAMPLE 37 Preparation of N-Hydroxy-4-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-4-imidazolidineacetamide. Step 1. Preparation of 4-(2-Methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazoUdineacetic Acid. Sodium hydroxide (300 mg, 7.50 mmol) is added to a solution of 2-(2- methylpropyl)-2-(propen-2-yl)glycine trifluoroacetic acid (856 mg, 3.00 mmol) which is prepared by the method described in J. Org. Chem., 1988, Vol. 53, p. 5607 and H 2 0 (10 mL). Phenethyl isocyanate (541 mg, 3.00 mmol) is added after 5 minutes and the mixture stirred for 1 hour at room temperature under N 2 . The solution is diluted with more H 2 0 (5 mL) and acidified with 6 N HCl. The resultant solution is heated at reflux for 2 hours. Upon cooling to room temperature, the desired product is extracted into CH 2 C1 2 (3 x 50 mL) and EtOAc (2 x 50 mL). The combined organic layers are dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to yield 619 mg of a golden oil. The oil is purified by siUca gel chromatography (50 g SG, packed and eluted with a gradient of 0-40% EtOAc/hexane) to give 162 mg (18%) of the hydantoin intermediate as an oil. The material is sufficiently pure to be carried on: 1H NMR (300 MHz, CDClg) δ 7.90- 8.60, 7.20-7.40, 5.75-5.95, 5.25-5.40, 3.15-3.30, 3.05-3.15, 2.60-2.90, 1.80-2.00, 0.90- 1.05. Sodium periodate (NaI0 4 , 883 mg, 4.13 mmol) is added to a mixture of H 2 0/CH 3 CN/CC1 4 (3/3/2 mL, respectively) and treated with ruthenium oxide monohydrate (14 mg, 20 mole %). Once the black solution has turned green, NaHCOg (2.17 g, 25.8 mmol) is added, foUowed by the further addition of NaI0 4 until the solution became green again. A solution of the hydantoin intermediate (155 mg, 0.516 mmol) in 3 mL CHgCN is added to the green mixture. After 5 minutes, the reaction mixture is quenched with H 2 0 and extracted with EtOAc several times. The aqueous layer is acidified with 6 N HCl and then extracted twice with CH 2 C1 2 (2 x) and EtOAc (2 x). The organic layers are combined, washed again with brine, dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to yield 79 mg of the title compound as a soUd. Additional title compound is recovered by washing the original EtOAc extracts with 10% NaOH, acidifying the aqueous with 6 N HCl, and re-extracting with CH 2 C1 2 (3 x). These extracts are also combined, washed again with brine, dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to yield an additional 64 mg of the title compound. Both crops are dissolved in CH 2 C1 2 , combined, filtered through a fine frit, and concentrated under reduced pressure to give a total of 143 mg (87%) of the title compound as a soUd. NMR (300 MHz, CDClg) δ 7.10-7.35, 3.70-3.80, 2.95, 2.66, 1.65-1.80, 1.40- 1.55, 0.88, 0.80. Step 2. Preparation of N-Benzyloxy-4-(2-methylpropyl)-2,5-dioxo-l-(2- phenylethyl)-4-imidazoUdineacetamide . A solution of 4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazoUdineacetic acid (126 mg, 0.379 mmol) in dry THF (5 mL) is treated with CDI (74.0 mg, 0.455 mmol). After 1 hour, 4-methylmorphoUne (417 μL, 3.79 mmol) and 0-benzyhydroxylamine hydrochloride (91.0 mg, 0.569 mmol) are added. The mixture is stirred for 12 hours at room temperature and is dfluted with EtOAc. The solution is washed with saturated NaHC0 3 , 1 N HCl, saturated NaHCOg, and brine. The organic layer is dried over anhydrous Na 2 S0 4 , filtered, and concentrated under reduced pressure to yield 156 mg of a black oil. The oU is purified by silica gel chromatography (25 g SG, packed with hexane, eluted with 50% EtOAc/hexane) to give 47 mg (28%) of the title compound as an amorphous white soUd. X H NMR (300 MHz, CDClg) δ 8.89, 7.15-7.45, 6.67, 4.70-5.00, 3.60-3.90, 2.95, 2.15-2.40, 1.50-1.70, 1.35-1.50, 0.84, 0.75; MS (FAB) m/z 424, 334, 318, 259, 105, 91. Step 3. Preparation of N-Hydroxy-4-(2-methylpropyl)-2 ,5-dioxo-l-(2- phenylethyl)-4-imidazoUdineacetamide. A solution of N-benzyloxy-4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazoUdineacetamide (85.0 mg, 0.201 mmol) in 25% MeOH/EtOAc is purged with N 2 , treated with paUadium hydroxide on carbon (17 mg, 20% by weight), and placed under a H 2 atmosphere (baUoon). After 2.5 hours, the reaction mixture is filtered through ceUte and concentrated under reduced pressure to yield 70 mg of an off- white foam. The material is recrystallized from hot EtOAc/hexane to give 36 mg (54%) of the title compound as a white, powdery solid (mp 145-147 °C). IR (mineral oil) 3284, 3227, 1762, 1719, 1707, 1662, 1655, 1424, 1365, 699 cm "1 ; NMR (300 MHz, CDClg) δ 7.84, 7.15-7.40, 3.60-3.85, 2.65-3.10, 2.35-2.55, 1.45-1.75, 0.90, 0.83; MS (El) m/z 333, 277, 259, 243, 229, 217, 155, 105, 104, 91. EXAMPLE 38 Preparation of N-Hydroxyl-4-(2-methylpropyl)-5-oxo-l-(2- phenylethyl)-4-pyrazoUdineacetamide monohydrochloride. Step 1. Preparation of l-(Benzyloxycarbonyl)-2-(2-phenylethyl)pyrazolidin-3- one. Sodium hydride (562 mg, 14.1 mmol, 60% mineral oil dispersion) is added to a solution of l-(benzyloxycarbonyl)pyrazoUdin-3-one (2.81 g, 12.8 mmol, prepared similarly to that described in J. Org. Chem. 1990, 55, 6037) and DMF (37 mL) at 0 °C. The solution is stirred for 30 minutes and then (2-bromoethyl)benzene (1.90 mL, 13.9 mmol) is added. The solution is stirred at 0 °C for 1 hour and 16 hours at room temperature. Aqueous workup (EtOAc, brine, MgS0 ) and purification by flash chromatography (2:1 → 1:1 hexane:EtOAc) gives 1.58 g (38%) of the title compound as an oU. IR (liq.) 3029, 2954, 1709, 1498, 1455, 1412, 1378, 1314, 1214, 1184, 1110, 1086, 1027, 748, 699 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.38, 7.10-7.30, 5.23, 4.02, 3.80, 2.87, 2.44; MS (El) mlz 324, 190, 189, 106, 105, 104, 92, 91, 79, 77, 65. Step 2. Preparation of l-(Benzyloxycarbonyl)-4-(2-methylpropen-2-yl)-2-(2- phenylethyl)pyrazolidin-3-one . Lithium dnsopropylamide (2.92 mL, 5.84 mmol, 2.0 M, heptane/THF/ethylbenzene) is added to a solution of l-(benzyloxycarbonyl)-2-(2- phenylethyl)pyrazolidin-3-one (1.58 g, 4.87 mmol), THF (15 mL), and HMPA (1.04 mL) at -78 °C. After stirring for 35 minutes at -78 °C, a solution of 3-bromo-2- methylpropene (0.54 mL, 5.4 mmol) and THF (2.6 mL) is added. The solution is aUowed to stir for 6 hours at -78 °C and is then quenched with aqueous ammonium chloride (25 mL). After warming to room temperature, aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (3:1 hexane:EtOAc) gives 1.21 g of the title compound (66%) as an oil. Further elution provides 201 mg of recovered starting material (75% of product based on recovered sm). Spectral data for the title compound: IR (liq.) 2945, 1710, 1498, 1455, 1416, 1377, 1318, 1232, 1206, 1172, 1121, 1028, 897, 748, 698 cm "1 ; l H NMR (300 MHz, CDClg) δ 7.38, 7.10-7.40, 5.23, 4.71, 4.53, 4.10-4.30, 4.01, 3.80-3.95, 3.09, 2.75-2.95, 2.60-2.80, 2.35-2.45, 1.63, 1.53; MS (El) mlz 378, 244, 243, 105, 104, 92, 91, 79, 77, 65. Step 3. Preparation of tert-Butyl 2-(Benzyloxycarbonyl)-4-(2-methylpropen-2- yl)-5-oxo- l-(2-phenylethyl)-4-pyrazoUdinacetate . Litl ium diisopropylamide (1.70 mL, 3.40 mmol, 2.0 M, heptane/THF/ethylbenzene) is added to a solution of l-(benzyloxycarbonyl)-4-(2- methylpropen-2-yl)-2-(2-phenylethyl)pyrazoUdin-3-one (1.20 g, 3.17 mmol), THF (15.6 mL), and HMPA (0.69 mL) at -78 °C. After stirring for 30 minutes at -78 °C, a solution of tert-butyl bromoacetate (0.57 mL, 3.5 mmol) and THF (1.5 mL) is added. The solution is allowed to stir for 6 hours at -78 °C and is then quenched with aqueous ammonium chloride (25 mL). After warming to room temperature, aqueous workup (EtOAc, MgS0 4 ) and purification by flash chromatography (4:1 → 3:1 hexane:EtOAc) gives 410 mg of the title compound (26%) as an oil. Further elution provides 624 mg of recovered starting material (55% of product based on recovered sm). Spectral data for the title compound. IB (neat) 1723, 1696, 1320, 1286, 1263, 1242, 1201, 1186, 1165, 1123, 906, 764, 749, 697, 604 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.35-7.45, 7.10-7.30, 5.19, 4.74, 4.68, 4.15-4.30, 3.88, 3.75-3.95, 2.80-2.95, 2.19, 2.17, 1.62, 1.41; MS (El) mlz 492, 302, 301, 283, 255, 105, 92, 91, 57. Step 4. Preparation of 2-(Benzyloxycarbonyl)-4-(2-methylpropen-2-yl)-5-oxo-l- (2-phenylethyl)-4-pyrazoUdineacetic Acid. TFA (8.0 mL) is added to a solution of tert-butyl 2-(benzyloxycarbonyl)-4-(2- methylpropen-2-yl)-5-oxo-l-(2-phenylethyl)-4-pyrazoUdinacetate (546 mg, 1.11 mmol) and CH 2 C1 2 (20 mL) at 0 °C. The solution is stirred for 1.5 hours at 0 °C and is concentrated. Aqueous workup (CH^CL^, MgS0 4 ) provides 456 mg (94%) of the title compound which is isolated as an oil. IR (mineral oU) 3069, 3061, 3031, 1719, 1651, 1422, 1405, 1329, 1238, 1207, 1134, 1027, 905, 755, 699, cm "1 ; X H NMR (300 MHz, CDClg) δ 7.39, 7.10-7.30, 5.19, 4.75, 4.68, 4.20-4.35, 3.80- 3.95, 3.77, 2.75-3.00, 2.10-2.40, 1.61; MS (El) mlz 436, 301, 255, 105, 104, 92, 91, 79, 77, 65, 57. Step 5. Preparation of N-Benzyloxy-2-(benzyloxycarbonyl)-4-(2-methylpropen- 2-yl)-5-oxo-l-(2-phenylethyl)-4-pyrazoUdineacetamide. CDI (204 mg, 1.26 mmol) is added to a solution of 2-(benzyloxycarbonyl)-4-(2- methylpropen-2-yl)-5-oxo-l-(2-phenylethyl)-4-pyrazolidineacetic acid (453 mg, 1.04 mmol) and CH 2 C1 2 (10 mL). The solution is stirred for 1 hour at room temperature and then O-benzylhydroxylamine hydrochloride (293 mg, 1.84 mmol) and N- methylmorphoUne (0.23 mL, 2.1 mmol) are added. The solution is stirred for 60 hours at room temperature. Aqueous workup (CH 2 C1 2 , MgS0 4 ) and purification by flash chromatography (1:1 hexane:EtOAc) provides 468 g (83%) of the title compound as an oil. IR (liq.) 3031, 1724, 1701, 1498, 1455, 1379, 1320, 1217, 1182, 1134, 1044, 1028, 749, 698, cm "1 ; X H NMR (300 MHz, CDClg) δ 8.72, 7.05-7.45, 5.18, 4.88, 4.73, 4.66, 4.05-4.30, 3.80-3.95, 3.57, 2.75-2.95, 1.95-2.20, 1.78, 1.57; MS (El) mlz 541, 407, 406, 106, 105, 104, 92, 91, 79, 77, 65. Step 6. Preparation of N-Hydroxyl-4- ( 2-methylpropyl ) -5-oxo-l-(2-phenylethyl)- 4-pyrazolidineacetamide monohydrochloride. An atmosphere of hydrogen is placed over a mixture of N-benzyloxy-2- (benzyloxycarbonyl)-4-(2-methylpropen-2-yl)-5-oxo-l-(2-phenylethyl)-4- pyrazoUdineacetamide (462 mg, 0.853 mmol), MeOH (34 mL) and Pearlman's catalyst (85 mg). After stirring for 8 hours at room temperature, the mixture is filtered, the soUds washed with MeOH (3 X 10 mL), CHgClg (10 mL), and the filtrates concentrated to provide 220 mg (81%) of the title compound as an oil. 1H NMR (300 MHz, CDClg) δ 10.3-10.5, 7.10-7.40, 3.45-3.80, 3.37, 2.80-3.00, 2.35, 1.45-1.90, 1.10-1.30, 0.88, 0.82. The hydrochloride salt is formed (EtOAc/MeOH) and triturated with ether to provide the hydrochloride salt of the title compound as a solid (mp 51-54°C). IR (mineral oil) 3172, 3061, 3028, 2724, 1714, 1655, 1604, 1585, 1556, 1498, 1414, 1282, 1227, 750, 701 cm "1 ; MS (El) mlz 319, 263, 245, 228, 172, 105, 104, 91, 57, 55. FoUowing the general procedures outlined in EXAMPLES 28,29 and making non-critical variations, the following compounds are prepared. EXAMPLE 39 Preparation of [S-(i?*-R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-N 1 -phenyl-α 1 -(phenylmethyl)- 1,3-pyrroUdinediacetamide. mp 169-172 °C; [α] D 25 -43° (c 0.54, MeOH); IR (mull) 3246, 3193, 3135, 3059, 3029, 1658, 1600, 1547, 1493, 1444, 1358, 1322, 1311, 759, 698 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.48, 7.10-7.35, 7.06, 4.74, 3.30-3.55, 3.05-3.25, 1.90- 2.40, 1.40-1.65, 1.20-1.35, 0.83, 0.75; MS (El) mle 364, 321, 273, 244, 228, 200, 132. EXAMPLE 40 Preparation of [S-(β*J2*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-ΛT 1 -(2-pyridinylmethyl)-l,3-pyrroUdinediacetamide. mp 68-71 °C; IR (mull) 3244, 3062, 3027, 1658, 1598, 1572, 1540, 1497, 1439, 1354, 1296, 1271, 751, 701, 620 cm "1 ; X H NMR (300 MHz, CDClg) δ 8.40-8.55, 7.90-8.00, 7.75, 7.50, 7.05-7.35, 4.35-4.70, 4.10-4.25, 3.25-3.50, 2.75-2.90, 2.15-2.40, 1.75-1.90, 1.40-1.65, 1.00-1.15, 0.86, 0.81; MS (El) mlz 436, 379, 336, 301, 244, 200, 147, 135, 92. EXAMPLE 41 Preparation of [S-(i2*- β *)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. mp 121-123 °C; IR (mull) 3240, 3178, 3086, 3064, 3028, 1664, 1593, 1512, 1498, 1422, 1331, 1294, 1210, 749, 701 cm "1 ; X H NMR (300 MHz, CDClg) δ 9.98, 8.25, 7.65-7.85, 7.15-7.35, 4.15-4.25, 3.25-3.65, 2.65-2.85, 2.37, 1.70-1.85, 1.45-1.70, 1.10-1.20, 0.90, 0.84; MS (El) mlz 438 (M + ) 317, 316, 301, 284, 200, 132, 105, 95, 91, 55. EXAMPLE 42 Preparation of [S-(i?*- β *)]-ΛT 1 -(4-Fluorophenyl)-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3-pyrroUdinediacetamide. mp 181-182.5; IR (mull) 3254, 3154, 3066, 1658, 1614, 1552, 1511, 1499, 1409, 1309, 1299, 1230, 1213, 836, 699 cm "1 ; 2 H NMR (300 MHz, CDClg) δ 8.20-8.50, 7.46, 7.15-7.40, 6.90-7.05, 4.65-4.80, 3.15- 3.50, 1.90-2.45, 1.40-1.70, 1.20-1.35, 0.87, 0.79; MS (El) mlz 455 (M + ) 345, 344, 317, 316, 284, 200, 132, 131, 91, 55. EXAMPLE 43 Preparation of [S-(i?* r β*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-iV 1 -[l-(phenylmethyl)-4-piperdinyl]-l,3- pyrroUdinediacetamide. mp 108-110 °C; IR (mull) 3276, 3107, 3085, 3062, 3027, 2764, 1658, 1540, 1496, 1296, 1271, 744, 721, 700 cm "1 ; MS (FAB) mlz 535 (MH + ), 534, 533, 519, 172, 91, 82. 5 EXAMPLE 44 Preparation of [S-(β*-R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-N 1 -(4-piperdinyl)-l,3-pyrroUdinediacetamide. 5 mp 160-165 °C; IR (mull) 3283, 3085, 3062, 3028, 1661, 1584, 1544, 1497, 1311, 1297, 1271, 1213, 1154, 748, 700 cm "1 ; MS (El) mlz 444 (M + ), 302, 301, 284, 132, 91, 84, 83, 82, 56, 55. EXAMPLE 45 Preparation of [S-(i?*J?*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(phenylmethyl)-N 1 -(4-pyridmylmethyl)-l,3-pyrroUdinediacetamide. mp 140.5-142 °C X H NMR (300 MHz, CDClg) δ 8.49, 8.35, 7.95-8.10, 7.10-7.35, 4.50-4.60, 4.20-4.45, 3.25-3.55, 2.80-3.10, 2.15-2.60, 1.95-2.10, 1.75-1.90, 1.40-1.70, 1.05-1.35, 0.89, 0.83; MS (FAB) m/z 453 (MH + ), 452, 437, 284, 132, 105, 93, 91. EXAMPLE 46 Preparation of [S-(β*J?*)]-N 1 -(4-Fluorophenylmethyl)-N 3 - hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3-pyrroUdinediacetamide. mp 64-66 °C X H NMR (300 MHz, CDClg) δ 7.05-7.35, 6.90-7.05, 4.50-4.70, 4.20-4.45, 3.10-3.45, 2.29, 1.80-2.10, 1.40-1.70, 1.10-1.30, 0.86, 0.80. EXAMPLE 47 Preparation of [S-(i?* f R*)]-iV 3 -Hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-α 1 -(2-phenylethyl)-l,3-pyrroUdinediacetamide. mp 148-148.5 °C; [α] D 25 -31° (c 0.68, MeOH); IR (mull) 3227, 3092, 3084, 3024, 1678, 1667, 1658, 1644, 1569, 1503, 1496, 1297, 1282, 1206, 703 cm '1 ; NMR (300 MHz, CDClg) δ 7.10-7.35, 6.29, 4.30, 3.35-3.50, 2.75, 2.45-2.65, 2.35, 2.00-2.30, 1.60-1.80, 1.35-1.60, 0.91, 0.86; MS (El) mle 316, 273, 258, 91, 44. EXAMPLE 48 Preparation of [S-(Λ* R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo-α 1 -(2-phenylethyl)-N 1 -(phenymιetnyl)-l,3-pyrroUdinediacetamide. mp 59-61°C; [α] D 25 -57° (c 0.39, CHClg); IR (mull) 3234, 3086, 3062, 3027, 1652, 1605, 1585, 1540, 1497, 1295, 1269, 1213, 1030, 739, 699 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.10-7.40, 6.40-6.55, 4.25-4.50, 3.25-3.50, 2.00-2.70, 1.25-1.75, 0.87, 0.83; MS (El) mlz 465 (M + ) 361, 332, 331, 330, 316, 298, 182, 117, 91. EXAMPLE 49 Preparation of [5-(ie*Je*)]-N 3 -Hydroxy-α 1 ,3-bis(2- methylpropyl)-2-oxo-N 1 -2-pyridinyl-l,3-pyrroUdinediacetamide. mp 73-75°C; IR (mull) 3203, 2728, 1663, 1600, 1579, 1532, 1494, 1435, 1298, 1279, 1181, 1152, 780, 741 cm "1 ; X l NMR (300 MHz, CDClg) δ 8.10-8.35, 7.72, 7.05, 4.25-4.40, 3.30-3.65, 2.35-2.60, 2.00-2.20, 1.35-1.95, 1.20-1.35, 0.75-1.10; MS (El) mlz 404 (M + ), 284, 283, 267, 250, 208, 149, 98, 56, 55. EXAMPLE 50 Preparation of [S-(i2* β*)]-α 1 -Cyclohexyl-N 3 -hydroxy-.V 1 - methyl-3-(2-methylpropyl)-2-oxo-l,3-pyrroUduιediacetamide. mp 199-200 °C; IR (mull) 3310, 3232, 3105, 1647, 1565, 1536, 1498, 1415, 1297, 1277, 1258, 1236, 1223, 1047, 722 cm "1 ; NMR (300 MHz, CDClg) δ 6.15-6.35, 4.01, 3.30-3.60, 2.76, 2.44, 2.20-2.40, 1.90- 2.15, 1.10-1.80, 0.90, 0.83; MS (El) mlz 367 (M + ) 336, 310, 309, 308, 277, 276, 154, 95, 58, 55. EXAMPLE 51 Preparation of [S-(i2*J2*)]-a 1 -Cyclohexyl-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-N 1 -2-pyridinyl-l,3-pyrroUdinediacetamide. mp 119-121 °C; IR (mull) 3254, 1665, 1596, 1579, 1532, 1497, 1434, 1301, 1279, 1270, 1186, 1172, 1151, 779, 740 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 8.25-8.35, 8.17, 7.65-7.80, 7.00-7.15, 4.20-4.35, 3.35- 3.60, 2.00-2.75, 0.70-1.85; MS (El) mlz 430 (M + ), 309, 294, 293, 276, 218, 154, 95, 78, 67, 55. EXAMPLE 52 Preparation of [S-(i2*J2*)]-3-(Cyclopentylmethyl)-iV 3 -hydroxy- iV 1 -methyl-2-oxo-α 1 -(phenylmethyl)-l,3-pyrroUdinediacetamide. mp 180-181.5 °C; NMR (300 MHz, CDClg) δ 7.10-7.40, 4.41, 3.10-3.45, 2.75, 2.70-3.05, 2.00-2.35, 1.85-2.00, 1.30-1.85, 0.85-1.15; MS (El) mlz 401, 343, 342, 328, 310, 200, 132, 91, 58. EXAMPLE 53 Preparation of [3S-[l( β *),3Λ*(Λ*)]]-α 3 -[2-(Benzoylamino)ethyl]- -V 3 -hydroxy-iV 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide. 1H NMR (300 MHz, CDClg) δ 7.70-7.85, 7.35-7.55, 7.05-7.35, 6.40, 4.80-5.00, 3.10- 3.50, 2.76, 2.20-2.40, 1.20-2.00, 0.70-1.00, 0.30-0.45; MS (FAB) mlz 523 (MH + ), 522, 391, 371, 129, 105, 71, 57, 43. EXAMPLE 54 Preparation of [S-(i2*J2*)]-N 3 -Hydroxy-3-(2-methylpropyl)-N 1 - [2-(4-morphoUnyl)ethyl]-2-oxo-α 1 -(phenylnιetnyl)-l,3-pyrroUdnιediacetamide. mp 66 °C; [α] D = -56° (c, 0.58; CHClg); IR (mull) 3223, 3086, 3063, 3027, 1653, 1547, 1497, 1297, 1271, 1239, 1146, 1118, 1071, 748, 700 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.45-7.15, 3.80-3.60, 3.50-3.00, 2.70-2.00, 1.95-1.80, 1.75-1.45, 1.35-1.15, 0.88; S (El) mlz 474 (M + ), 418, 358, 345, 244, 200, 113, 100. EXAMPLE 55 Preparation of [S-(B*J**)]-N-Hydroxy-3-(2-methylpropyl)-l-[2- (4-morphoUnyl)-2-oxo-l-(phenylmethyl)ethyl]-2-oxo-3-pyrroUdineacetamide. mp 52-56 °C); tα] D = -82° (c, 0.70; CHClg); IR (mull) 3237, 3085, 3061, 3025, 1648, 1494, 1299, 1268, 1239, 1213, 1115, 1039, 1029, 751, 702 cm "1 ; MS (El) mlz 431 (M + ), 399, 375, 357, 344, 340, 317, 284, 114, 91; X H NMR (CDClg) δ 7.35-7.15, 5.30, 3.70-3.10, 3.10-2.90, 2.40-1.95, 1.85-1.15, 0.86; HRMS (El) 431.2436. EXAMPLE 56 Preparation of [l(LS)-[l[#*(fl*)], 3α,5α]]-l-[2-(3,5-Dimethyl-l- piperazinyl)-2-oxo-l-(phenylmethyl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetamide. mp 106 °C; [α] D = -77° (c, 0.6082; CHClg); HI (muU) 3252, 3087, 3062, 3027, 1649, 1493, 1323, 1263, 1193, 1157, 1110, 1084, 1033, 751, 702 cm '1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.35-7.10, 5.40-5.25, 4.50-4.35, 3.95-3.65, 3.55-3.30, 3.30-2.95, 2.75-0.75; MS (El) mlz 458 (M + ), 402, 317, 113, 84. EXAMPLE 57 Preparation of [S-(i?*J2*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2- oxo- 1 -(phenylmethyl)-Λ^ 1 -2-pyridinyl-l,3-pyrroUdinediacetamide. mp 171-174 °C; [α] D = -14° (c, 0.67; CHClg); IR (mull) 3057, 3030, 3010, 1706, 1661, 1642, 1614, 1586, 1558, 1315, 1282, 1205, 786, 753, 704 cm '1 ; l K NMR (300 MHz, CDClg) δ 8.40-8.30, 8.25-8.15, 7.85-7.75, 7.40-7.20, 7.20-7.05, 4.26, 3.60-3.35, 2.80-2.65, 2.55-2.25, 1.90-1.40, 1.10-1.95, 0.87; MS (El) m lz 438 (M + ), 406, 382, 364, 347, 317, 284, 226, 200, 132, 91. EXAMPLE 58 Preparation of [3S-[l( β *),3i2*(ϋ;*)]]-α 3 -t2-(l,3-Dihydro-l,3-dioxo- 2H-isoindol-2-yl)ethyl]-N 3 -hydroxy-- * V 1 -methyl-3-(2-methylpropyl)-2-oxo- 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide. 1H NMR (300 MHz, CDClg) δ 7.65-7.95, 7.10-7.40, 6.20, 4.55-4.70, 3.05-3.75, 2.67, 1.15-2.30, 0.77, 0.68; S (FAB) mlz 549 (MH + ), 550, 549, 517, 516, 429, 160, 69, 57, 55, 43. EXAMPLE 59 Preparation of [S-(B*-R*)]-α 1 -Cyclohexyl-N 1 -cyclopropylmethyl- N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. mp 140-144°C; 1H NMR (300 MHz, CDClg) δ 6.40, 3.97, 3.50-3.65, 3.30-3.45, 2.50-2.70, 2.20-2.40, 1.90-2.15, 1.10-1.90, 0.65-1.00, 0.40-0.60. EXAMPLE 60 Preparation of [S-(JΪ*Ji*)]-α 1 -Cyclohexyl-iv '1 -(4-fluorophenyl)- N -hydroxy-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. mp 132-135 °C; l H NMR (300 MHz, CDClg) δ 8.47, 7.40-7.50, 6.99, 4.15, 3.35-3.65, 2.57, 2.30-2.45, 2.00-2.20, 0.95-1.85, 0.86, 0.77. FoUowing the general procedures outlined in EXAMPLES 30-34 and making non-critical variations, the foUowing compounds are prepared. EXAMPLE 61 Preparation of [S-(i?*J2*)]- 1 -tert-Butyl-N 3 -hydroxy-N 1 -methyl- 3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. mp 108-110 °C; NMR (300 MHz, CDClg) δ 5.80-6.00, 4.23, 4.15-4.35, 2.70-2.80, 2.45-2.70, 2.30- 2.45, 1.85-2.30, 1.35-1.85, 1.05, 0.75-1.00; MS (ESI) 340 (MET). FoUowing the general procedures outlined in EXAMPLES 4-14 and making non-critical variations, the following compounds are prepared. EXAMPLE 62 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-(5-propyloxy-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3- pyrroUdineacetamide . mp 137-138 °C; ER (mineral ofl) 3211, 3085, 3028, 1772, 1712, 1660, 1620, 1491, 1400, 1346, 1292, 1249, 1234, 749, 705 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.72, 7.05-7.40, 4.02, 3.35-3.80, 3.10-3.25, 2.78, 2.30- 2.45, 2.05-2.30, 1.75-2.00, 1.35-1.70, 1.06, 0.83, 0.76; MS (El) mlz 549 (M+), 493, 489, 262, 261, 245, 244, 218, 202, 176, 105. EXAMPLE 63 Preparation of [R-(R*,S*)]-5-Fluoro-l,3-dihydro-N-hydroxy-α-[3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l,3-dioxo-2H-isoindole-2- butan amide. IR (mull) 3205, 3063, 3027, 1775, 1717, 1664, 1616, 1497, 1481, 1399, 1302, 1263, 1229, 747, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 8.92, 7.83, 7.50, 7.00-7.45, 3.35-3.80, 3.25-3.35, 3.10- 3.25, 2.79, 2.55-2.70, 2.30-2.50, 2.10-2.30, 1.70-2.00, 1.35-1.65, 0.70-1.00; MS (El) mlz 509 (M + ), 477, 453, 449, 345, 262, 261, 178, 105, 104. EXAMPLE 64 Preparation of α-[2-(5,6-Difluoro-l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. IR (mull) 3340, 3187, 3062, 3028, 1777, 1720, 1678, 1654, 1505, 1406, 1354, 1277, 1261, 746, 704 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.55-7.70, 7.40-7.55, 7.05-7.40, 3.35-3.80, 3.10-3.35, 2.70-2.85, 2.55-2.70, 2.30-2.55, 2.05-2.30, 1.70-2.05, 1.35-1.70, 0.85, 0.79; MS (El) mlz 527 (M + ), 471, 467, 363, 262, 261, 202, 196, 105, 104. EXAMPLE 65 Preparation of iV-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-(5-trifluoromethyl-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3- pyrroUdineacetamide. mp 137-138 °C; IR (mull) 1715, 1659, 1494, 1444, 1398, 1348, 1323, 1307, 1295, 1266, 1184, 1140, 1101, 750, 694 cm "1 ; X H NMR (CDClg) δ 8.91, 8.05-8.15, 7.90-8.05, 7.37, 7.05-7.35, 3.35-3.85, 3.25-3.35, 3.10-3.25, 2.79, 2.55-2.70, 2.35-2.55, 2.10-2.35, 1.75-2.05, 1.30-1.70, 0.84, 0.78; MS (El) m/z 559 (M + ), 527, 503, 499, 395, 262, 261, 228, 105, 104. EXAMPLE 66 Preparation of α-[2-(l,3,4,5,6,7-Hexahydro-l,3-dioxo-2H- isoindol-2-yl)ethyl]-iV-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. mp 118-119 °C; IR(mull) 3167, 3088, 3065, 3028, 1703, 1668, 1497, 1443, 1393, 1346, 1331, 1306, 1296, 1279, 701 cm "1 ; 1H NMR(300 MHz, CDClg) δ 8.80, 7.45, 7.10-7.40, 3.35-3.65, 3.10-3.35, 2.70-2.95, 2.50-2.70, 2.10-2.50, 1.25-2.10, 0.85, 0.79; MS (El) mlz 497 (M + ), 465, 441, 437, 262, 261, 244, 105, 104, 81. EXAMPLE 67 Preparation of α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethylj-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(3-phenylpropyl)-3- pyrroUdineacetamide. mp 163-165 °C): IR (mineral oil) 3231, 3107, 3088, 3051, 3034, 1771, 1712, 1683, 1663, 1499, 1442, 1400, 1298 cm "1 ; λ H NMR (300 MHz, CDClg) δ 7.75-7.90, 7.65-7.75, 7.10-7.30, 3.60-3.85, 3.10-3.40, 2.56, 1.35-2.45, 0.87, 0.80; MS (El) mlz 505 (M + ), 387, 386, 276, 259, 258, 216, 185, 130, 91, 56. EXAMPLE 68 Preparation of l-[2-(4-Fluorophenyl)ethyl]-α-[2-(l,3-dihydro-l,3- dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3- pyrroUdineacetamide. mp 142.5-144 °C; (mineral oil) 3212, 3067, 1773, 1712, 1673, 1657, 1510, 1495, 1438, 1398, 1341, 1301, 1219, 1034 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.60-7.95, 7.05-7.25, 6.85-7.05, 3.20-3.85, 3.10-3.25, 2.76, 1.30-2.50, 1.21, 0.82, 0.75; MS (El) mlz 509 (M + ), 477, 453, 449, 400, 220, 160, 123. EXAMPLE 69 Preparation of α-[2-(o-benzoic sul£mide)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. mp 144-144.5 °C; IR (mull) 3257, 1739, 1656, 1492, 1334, 1326, 1298, 1279, 1264, 1181, 1178, 1163, 1126, 752, 674 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.75-8.15, 7.00-7.40, 3.35-4.05, 3.10-3.30, 2.70-2.90, 2.40-2.60, 1.20-2.35, 0.65-1.00; MS (El) mlz hΥl (M + ) 495, 471, 261, 245, 244, 202, 105, 104, 81, 56. EXAMPLE 70 Preparation of Ethyl Phenylmethyl [4-(hydroxyamino)-3-[3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrrolidinyl]-4-oxobutyl]imidodicarbonate. S (El) m/e 568. FoUowing the general procedures outUned in EXAMPLES 4-14 and making non- critical variations, but starting with the diastereomer of tert-butyl α-(2- hydroxyethyl)-3-(2-methylpropyl)-2-oxo-l-(2-phenyIethyl)-3-pyrroUdineacetate (EXAMPLE 4, step 2), the following compounds are prepared. EXAMPLE 71 Preparation of [5-(i?*J2*)]-l,3-Dihydro-N-hydroxy-α-[3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l,3-dioxo-2H-isoindole-2- butanamide. IR (mull) 1716, 1660, 1644, 1401 cm "1 ; X H NMR (300 MHz, CDClg) δ 9.84, 7.80-7.90, 7.65-7.80, 7.15-7.35, 3.70-3.80, 3.35- 3.70, 3.05-3.25, 2.80, 2.40-2.55, 2.34, 1.85-2.10, 1.30-1.65, 0.79, 0.71; MS (El) mle 491, 459, 373, 245, 202, 185, 105. EXAMPLE 72 Preparation of l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-[2-(4-fluorophenyl)ethyl]-3-pyrroUdinyl]-l,3-dioxo-2H-isoindole-2-butanamide. IR (mull) 3223, 1716, 1675, 1648, 1510, 1444, 1397, 1367, 1218, 722 cm '1 ; MS (El) m le 509, 477.453, 449, 400, 262, 220, 160, 123. EXAMPLE 73 Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-iV- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pvrroUdineacetamide. Step 1. Preparation of tert-Butyl α-(2-Aminoethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdineacetate. DEAD (1.18 mL) is added to a solution of tert-butyl α-(2-hydroxyethyl)-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 4, step 2; 2.74 g, 6.79 mmol), dibenzyl iminodicarboxylate (2.14 g), triphenylphosphine (1.96 g) and THF (43 mL). The mixture is stirred for 16 hours at room temperature. The solution is concentrated and purified by flash chromatography (3:1 hexane EtOAc) to give 3.09 g (68%) of the imide as an oil: IR (neat) 2957, 1799, 1751, 1723, 1686, 1498, 1455, 1387, 1367, 1335, 1331, 1287, 1213, 1188, 1153, 1108, 1092, 698 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.15-7.40, 5.23, 3.55-3.90, 3.25-3.40, 3.19, 2.79, 2.47, 2.30-2.45, 1.75-1.95, 1.50-1.70, 1.39, 0.82, 0.79; MS (FAB) m lz 671 (MH + ), 616, 572, 420, 419, 105, 92, 91, 57. A mixture of the imide (1.01 g, 1.51 mmol), EtOH (100 mL), and 10% Pd/C (250 mg) is hydrogenated at 32 psi for 16 hours. The mixture is filtered, the soUds washed with EtOH (20 mL), CH 2 C1 2 (20 L), and EtOH (20 mL). The combined filtrates are concentrated to provide 549 mg (91%) of the title compound as an oil: 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.55-3.70, 3.30-3.45, 3.15-3.30, 2.30-2.90, 1.92, 1.35-1.85, 0.87, 0.83. Step 2. Preparation of tert-Butyl α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate. To a solution of tert-butyl α-(2-aπύnoethyl)-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrrolidineacetate (549 mg, 1.36 mmol), CH 2 C1 2 (8.4 mL), and diisopropylethylamine (0.29 ml, 1.6 mmol) at 0 °C is added 3,4-difluorobenzoyl chloride (0.21 mL, 1.6 mmol). The solution is stirred at 0 °C for 1 hour and 16 hours at room temperature. Basic workup (CH 2 C1 2 , NaHCOg, MgS0 4 ) and purification by flash chromatography (1:1 hexane.ΕtOAc) gives 477 mg (64%) of the title compound as a white solid (mp 147-148 °C): IR (mull) 3365, 1717, 1657, 1606, 1549, 1509, 1497, 1319, 1295, 1282, 1229, 1199, 1152, 832, 774 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.65-7.80, 7.50-7.60, 7.15-7.40, 6.55-6.70, 3.55-3.70, 3.20-3.50, 2.81, 2.50-2.60, 2.10-2.40, 1.75-1.90, 1.40-1.65, 1.43, 0.85, 0.79; MS (El) mlz 542 (M + ) 486, 396, 395, 260, 245, 202, 141, 105, 104, 57. Step 3. Preparation of α-[2-[(3, 4-Difluorobenzoyl)amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrrolidineacetic Acid. A solution of tert-butyl α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylet_hyl)-3-pyrrolidineacetate (473 mg, 0.872 mmol), CH 2 C1 2 (5.0 mL), and TFA (5.0 mL) is stirred for 1 hour at 0 °C and 2 hours at room temperature. The solution is concentrated and the residue resuspended in CH 2 C1 2 and reconcentrated two additional times (2 x 20 mL). Aqueous workup (CEtgCl^ MgS0 4 ) provides 420 mg (99%) of the title compound as an oU: IR (liq.) 2959, 1728, 1661, 1618, 1607, 1553, 1510, 1467, 1454, 1443, 1442, 1314, 1297, 1283, 1203 cm "1 ; NMR (300 MHz, CDClg) δ 7.65-7.75, 7.50-7.60, 7.15-7.40, 6.75-6.90, 3.70-3.90, 3.60-3.70, 3.40-3.55, 3.20-3.40, 2.80-3.00, 2.52, 1.95-2.10, 1.50-1.90, 1.15-1.35, 0.91, 0.83; MS (El) mlz 486 (M + ), 395, 272, 259, 258, 247, 141, 113, 105, 104. Step 4. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUo!ineacetamide. EDC (193 mg) is added to a solution of α-[2-[(3,4- difluorobenzoyl)amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetic acid (411 mg, 0.865 mmol), CH 2 C1 2 (8.7 mL), DMF (2.1 mL), HOBT (118 mg), and 4-methylmorphoUne (0.11 ml) at 0 °C. The solution was stirred for 5 min at 0 °C and 50 min at room temperature. Hydroxylamine hydrochloride (121 mg) and 4-methylmorphoUne (0.19 mL) are added and the solution stirred for 16 hours at room temperature. The solution is diluted with 20 mL of water and the mixture acidified to pH 5 with 1 N HCl. The mixture is extracted several times with CH 2 C1 2 (3 x 20 L), the combined organic layers dried (MgS0 4 ), filtered, and concentrated. The residue is purified by flash chromatography (10:1 CH 2 G 2 :MeOH) to give 273 mg of an oil which is crystalUzed from EtOAc/hexane to give 164 mg (38%) of the title compound as a white powder (mp 132.5-134 °C): IR (mull) 3264, 1674, 1666, 1649, 1512, 1497 cm "1 ; l H NMR (300 MHz, CDClg) δ 7.60-7.80, 7.50-7.60, 7.05-7.35, 3.15-3.65, 2.81, 2.48, 1.85-2.20, 1.40-1.75, 0.85, 0.79; MS (El) mle 501, 469, 262, 245, 202, 141, 105. Following the general procedures outUned in EXAMPLE 73 and making non- critical variations, the foUowing compounds were prepared. EXAMPLE 74 Preparation ot [i?-(i2*,S" t )-α-[2-[(3-Fluorobenzoyl)amino]ethyl]- iV-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. mp 144-145 °C; [α]r 25 0 +13° (c 0.75, CHClg); IR (mull) 3290, 3216, 3062, 3029, 1673, 1662, 1643, 1585, 1555, 1496, 1486, 1323, 1301, 1227, 698 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.45-7.60, 7.10-7.45, 6.97, 3.35-3.70, 3.15-3.30, 2.83, 2.40-2.55, 1.80-2.05, 1.40-1.70, 0.87, 0.80; MS (El) mlz 483 (M + ), 451, 262, 245, 202, 154, 123, 105, 104, 95, 56. EXAMPLE 75 Preparation of α-[2-[(4-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. IR (mull) 2950, 2932, 1718, 1661, 1604, 1547, 1504, 1466, 1454, 1234 cm" 1 . EXAMPLE 76 Preparation of N-Hydroxy-3-(2-methylpropyl)-α-[2-[(3- nitrobenzoyl)anιino]ethyl]-2-oxo-l-(2-phenylethyl)-3-pvrroUdineacetamide. IR (mull) 3270, 1664, 1633, 1556, 1532, 1454, 1447, 1351, 1310, 698 cm "1 ; MS (El) mle 510. EXAMPLE 77 Preparation of α-[2-[(3-Fluorobenzoyl)amino]ethyl]-iV-hydroxy-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. mp 157-159 °C ; IR (mull) 2954, 2925, 2868, 2855, 1645, 1624, 1586, 1552, 1465, 1455 cm '1 ; MS (EI) m/e 03. EXAMPLE 78 Preparation of α-[2-[(3-Fluorobenzoyl ) amino]ethyl]-l-[2-(4- fluorophenyl)ethyl]-N-hydroxy-3-(2-methylpropyl ) -2-oxo-3-pyrroUdineacetamide. IR (mull) 2954, 2924, 2855, 1662, 1586, 1544, 1510, 1484, 1462, 1224 cm "1 . EXAMPLE 79 Preparation of α-[2-[(4-BiphenylcarbonyI)aminoJethyl]-iV-hydroxy-3-(2- methylpropyl )-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide. S (El) TO /e MH + 542. EXAMPLE 80 Preparation of N-Hydroxy-α-[2-t[(4- methylphenyl)sulfonyl]amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. Step 1. Preparation of tert-Butyl α-[2-[[(4-Methylphenyl)sulfonyl]amino]ethyl]- 3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrrolidineacetate. Toluenesulfonyl chloride (372 mg) is added to a solution of tert-butyl α-(2- ammoethyl)-3-(2-metJιylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 73, step 1; 654 mg, 1.62 mmol), CH 2 C1 2 (10.0 mL), and dnsopropylethylamine (0.34 mL) at 0 °C. The solution is stirred at 0 °C for 1 hour and at room temperature for 16 hours. Basic workup (CH 2 C1 2 , NaHCOg, MgS0 4 ) and purification by flash chromatography gives 634 mg (70%) of the title compound as a white solid (mp 136-138 °C): IR (mineral oil) 1710, 1674, 1366, 1329, 1303, 1156, 1101 cm "1 ; NMR (300 MHz, CDClg) δ 7.73, 7.15-7.35, 4.45-4.55, 3.50-3.70, 3.30-3.45, 3.15-3.30, 2.75-3.10, 2.42, 2.20-2.35, 1.80-1.95, 1.60-1.80, 1.30-1.60, 1.38, 0.84, 0.79; MS (FAB) mlz 557 (MH + ), 503, 502, 501, 484, 483, 105, 91, 57. Step 2. Preparation of α-[2-[[(4-Methylphenyl)sulfonyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic Acid. TFA (7.0 mL) is added to a solution of tert-butyl α-[2-[[(4- methylphenyl)sulfonyl]amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (616 g, 1.11 mmol) and CH 2 C1 2 (7.0 mL) at 0 °C. The solution is stirred for 1 h at 0 °C and for 2 hours at room temperature. The solution is concentrated which is repeated twice more from CH 2 C1 2 (2 x 20 mL). Aqueous workup (CH 2 C1 2 , MgS0 4 ) provides 463 mg (84%) of the title compound as a white foam: IR(mineral oil) 1733, 1615, 1503, 1498, 1481, 1330, 1305, 1288, 1160, 1094, 701 cm" 1 ; 1H NMR (300 MHz, CDClg) δ 7.70-7.80, 7.15-7.40, 4.80-5.00, 3.70-3.90, 3.20-3.50, 2.65-3.10, 2.50-2.65, 2.42, 1.95-2.10, 1.80-1.95, 1.50-1.80, 1.00-1.20, 0.92, 0.85; MS (El) mlz 500 (M + ), 426, 392, 391, 334, 327, 244, 155, 105, 104, 91. Step 3. Preparation of N-Benzyloxy-α-t2-[[(4- methylphenyl)sulfonyl]amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. CDI (162 mg) is added to a solution of α-[2-[[(4- methylphenyl)sulfonyl]amino]ethyl]-3- ( 2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetic acid (453 mg) and CH^L j (5.0 mL). The solution is stirred for 1 hour at room temperature and then 0-benzylhydroxylamine hydrochloride (192 mg) and 4-methylmorphoUne (0.13 mL) are added. The solution is stirred for 16 h at room temperature. The solution is dUuted with 60 mL of EtOAc which is washed with 10% HCl, brine, dried (MgS0 4 ), filtered, and concentrated. Purification by flash chromatography (1:1 hexane:EtOAc) provides a lactam intermediate with no evidence of O-benzylhydroxylamine incorporation: 1H NMR (300 MHz, CDC1 3 ) δ 7.86, 7.15-7.45, 3.85-4.00, 3.45-3.70, 3.18, 2.85, 2.60- 2.80, 2.43, 1.80-2.15, 1.35-1.55, 0.70-0.95. A solution of the bis-lactam intermediate (317 mg, 0.657 mmol), O-benzy ydroxylamine (500 mg) and THF (4.0 mL) is heated at reflux for 72 hours and then aUowed to cool to room temperature. The residue is diluted with EtOAc which is washed with 10% HCl (2 x 10 mL) and brine (10 mL). The organic layer is dried (MgS0 4 ), filtered, and concentrated. Purification by flash chromatography (1:1 hexane:EtOAc) and CrystaUization from ether provides 139 mg (35%) of the title compound as a white crystaUine material (mp 155-157 °C): IR (mull) 3162, 1664, 1650, 1332, 1154, 704 cm "1 ; X rl NMR (300 MHz, CDClg) δ 7.71, 7.15-7.40, 4.97, 4.81, 3.35-3.65, 3.17, 2.75-3.00, 2.55-2.75, 2.30-2.45, 2.39, 1.80-2.05, 1.35-1.70, 0.84, 0.77; MS(EI) mle 605, 483, 433, 327, 245, 202. Step 4. Preparation of iV-Hydroxy-α-[2-[[(4- methylphenyl)sulfonyl]amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. A mixture of N-benzyloxy-α-[2-[[(4-methylphenyl)sulfonyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (133 mg, 0.220 mmol), MeOH (8.0 mL), and Pearlman's cat (25 mg) is hydrogenated (1 atm) for 8 h at room temperature. The mixture is filtered, the soUds washed with MeOH (2 x 5 mL), CE^CLg (5 mL), and MeOH (5 mL). The combined filtrates are concentrated and the residue crystalUzed from EtOAc/hexane to give 84 mg (74%) of the title compound as a white solid (mp 166.5-167 °C) : IR (mull) 3278, 3202, 3028, 1659, 1636, 1496, 1329, 1298, 1291, 1160, 1093, 1061, 816, 702, 656 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.72, 7.30-7.60, 7.15-7.35, 5.82, 3.40-3.70, 3.15-3.35, 2.95-3.10, 2.70-2.95, 2.81, 2.57, 2.40, 2.10-2.25, 1.80-2.00, 1.30-1.75, 0.86, 0.80; MS (El) mlz 515 (M + ), 483, 391, 343, 245, 244, 202, 155, 105, 104, 91. Following the general procedures outlined in EXAMPLE 80 and making non- critical variations, the foUowing compounds are prepared. EXAMPLE 81 Preparation of α-[2-[[(4-Fluorophenyl)sulfonyl]amino]ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. IR (muU) 3195, 3026, 1661, 1634, 1593, 1496, 1333, 1259, 1238, 1166, 1157, 1095, 1060, 844, 702 cm "1 ; 1H NMR (300 MHz, CDClg) δ 8.79, 7.75-7.90, 7.50-7.70, 7.43, 7.10-7.30, 3.10-3.50, 2.68, 2.40-2.75, 2.05-2.20, 1.85-2.00, 1.50-1.70, 1.30-1.50, 1.15-1.30, 0.75, 0.66; MS (El) mlz 519 (M + ), 395, 245, 202, 159, 154, 110, 105, 104, 95, 56. EXAMPLE 82 Preparation of N-Hydroxy-α-[2-[[(4- methoxyphenyl)sulfonyl]amino]ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide . S (EI) m/e 532 (MH + ). EXAMPLE 83 Preparation of N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-α-[2-[(phenylsulfonyl)an ino]ethyl]-3-pyrroUdineacetamide. IR (mull) 2954, 2924, 2862, 2855, 1663, 1610, 1569, 1453, 1446, 1429 cm "1 ; MS (EI) m/e 502 (MH + ). EXAMPLE 84 Preparation of [«-(i?*,S* )]-α-[2-[[(4- Fluorophenyl)sulfonyl]anήno]ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetamide. mp 67-70 °C; HI(mull) 3196, 3107, 3065, 3027, 1662, 1592, 1495, 1332, 1292, 1237, 1166, 1154, 1093, 839, 701cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.80-7.95, 7.40-7.70, 7.10-7.40, 5.90, 3.10-3.70, 3.00-3.15, 2.70-3.00, 2.55, 2.05-2.20, 1.80-2.00, 1.20-1.80, 0.85, 0.80; MS (FAB) m/z 520 (MH + ), 519, 504, 488, 487, 343, 202, 105. EXAMPLE 85 Preparation of 5,6-Difluoro-l,3-dihydro-N-hydroxy-α-[3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2- butanamide. Step 1. Preparation of tert-Butyl α-[2-(3-Acetoxy-5,6-difluoro-l,3-dihydro-l-oxo- 2H-isoindol-2-yl)ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate. Sodium borohydride (26 mg, 0.68 mmol) is added to a solution of tert-butyl α- [2-(5,6-difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate (EXAMPLE 64; 384 mg, 0.675 mmol) and methanol (2.4 mL) at room temperature. The solution is stirred overnight at room temperature. Aqueous workup (EtOAc, MgS0 4 ) provides 386 mg (100%) of the diastereomeric mixture as a white foam. SoUd 4-dimethylaminopyridine (14 mg, 0.12 mmol) is added to a solution of the crude alcohol (336 mg, 0.590 mmol), triethylamine (0.49 mL, 3.5 mmol), acetic anhydride (0.28 mL, 3.0 mmol) and CH 2 C1 2 (6.0 mL). The solution is stirred at room temperature for 2 hours. The reaction mixture was diluted with ether and the ether is washed with 10% HCl, saturated NaHCOg, dried over MgS0 4 , filtered, and concentrated. Column chromatography (20 → 50% EtOAc/hexane) provides 273 mg (76%) of the title compound as a diastereomeric mixture as an oil: MS (El) m z 612 (M + ) 497, 496, 440, 406, 405, 245, 236, 202, 105, 57. Step 2. Preparation of tert-Butyl 5,6-Difluoro-l,3-dihydro-α-[3-(2- methylpropyl ) -2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butyrate. A mixture of tert-butyl α-[2-(3-acetoxy-5,6-difluoro-l,3-dihydro-l-oxo-2H- isoindol-2-yl ) ethyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (236 mg, 0.386 mmol), paUadium on carbon (10%, 60 mg) and acetonitrile (30 L) is hydrogenated at 35 psi for 2 hours. The mixture was filtered and concentrated. Aqueous workup (EtOAc, MgS0 4 ) gave 200 mg (93%) of the title compound as an oU: MS (El) m/z 554 (M + ) 499, 498, 481, 408, 407, 247, 202, 182, 105, 57. Step 3. FoUowing the general procedure outlined in EXAMPLE 1, steps 4 and 5, and making non-critical variations, but starting with tert-butyl 5,6-difluoro-l,3- dihydro-α-[3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdinyl]- l-oxo-2H- isoindole-2-butyrate, the title compound is obtained: (mp 175-176 °C): IR (mull) 3186, 3060, 3022, 1702, 1659, 1511, 1436, 1307, 1290, 1265, 1219, 762, 757, 707, 699 cm "1 ; 1H NMR (300 MHz, CDClg) δ 8.80, 7.45-7.60, 7.05-7.35, 4.30-4.60, 3.05-3.75, 2.60- 2.80, 1.30-2.60, 0.87, 0.78; MS (El) m/z 513 (M + ) 514, 513, 480, 423, 262, 244, 236, 202, 182, 105. FoUowing the general procedures outUned in EXAMPLE 85 and making non- critical variations, the foUowing compounds are prepared. EXAMPLE 86 Preparation of l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrrolidmyl]- l-oxo-2i_T-isoindole-2-butanamide. mp 140-144 °C; IR (mull) 3165, 3085, 3058, 3020, 1683, 1669, 1653, 1616, 1487, 1424, 1349, 1335, 1295, 738, 699 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.80, 7.35-7.55, 7.00-7.35, 4.30-4.55, 3.10-3.85, 2.60-2.80, 1.90-2.40, 1.45-1.85, 0.87, 0.76; MS (El) mlz 477 (M + ), 202, 200, 189, 146, 134, 105, 104, 91, 56. EXAMPLE 87 Preparation of [i2-(i?*,S*)]-6-Fluoro-l,3-dUιydro-iV-hydroxy-α-[3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2- butan amide. mp 167-170 °C; 1H NMR (300 MHz, CDClg) δ 7.48, 7.35-7.45, 7.05-7.35, 4.30-4.50, 3.10-3.80, 2.55- 2.95, 1.15-2.55, 0.87, 0.77; MS (ESI) 496 (MH + ). EXAMPLE 88 Preparation of [ie-(i?*,S*)]-5-Fluoro-l,3-dihydro-iV-hydroxy-α-[3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrrolidinyl]-l-oxo-2H-isoindole-2- butanamide. mp 135-136 °C; 1H NMR (300 MHz, CDC1 3 ) δ 7.70-7.85, 7.44, 7.00-7.35, 4.30-4.55, 3.05-3.80; 2.55- 2.80, 2.35-2.55, 1.85-2.35, 0.87, 0.76; MS (ESI) 496 (MH + ). EXAMPLE 89 Preparation of [R-(R* ,S* )]-5,6-Difluoro- 1,3-dihydro-iV-hydroxy- α-[3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2- butanamide. mp 153.5-155°C; X H NMR (300 MHz, CDClg) δ 8.98, 7.50-7.65, 7.43, 7.00-7.35, 4.50, 3.10-3.75, 2.60- 2.80, 2.45-2.60, 2.25-2.45, 1.85-2.25, 1.40-1.85, 0.87, 0.79; MS (ESI) 514 (MH + ). EXAMPLE 90 Preparation of N-Hydroxy-α-[[[(4- methoxyphenyl)sulfonyl]amino]methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide (cR-diastereomer). Step 1. Preparation of tert-Butyl α-(l-Hydroxymethyl)-3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrrolidineacetate (αS-diastereomer). A cold (-78 °C) solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate (EXAMPLE 1, step 3; 2.00 g, 5.56 mmol) in dry THF (20 mL) is treated with the dropwise addition of LDA (3.20 mL, 6.40 mmol, 2.0 N). The solution is maintained at -78 °C for 30 min and then warmed to -30 °C. Gaseous formaldehyde (generated by heating 834 mg of paraformaldehyde at 160 °C to provide approximately 28 mmol) is bubbled through the enolate solution. The solution is maintained at -30 °C for 1 hour and then quenched with saturated aqueous NH 4 C1 (5 mL) and diluted with H 2 0 (20 mL). The product is extracted into EtOAc (3 X 50 mL), dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide 2.52 g of a yeUow soUd which is purified by silica gel chromatography (100 g SG; 25% EtOAc/hexane) to give 1.43 g (83%) of the title compound as a golden ofl. Another fraction containing 375 mg of a mix of both diastereomers is also recovered. Spectral data for the title compound: IR (Uq.) 3417, 2957, 2931, 2869, 1722, 1669, 1497, 1465, 1455, 1392, 1368, 1274, 1252, 1155, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.40, 3.90-4.05, 3.70-3.80, 3.55-3.70, 3.40-3.55, 3.20-3.30, 2.85, 2.75, 2.69, 2.00-2.20, 1.90-2.00, 1.65-1.70, 1.50-1.60, 1.44, 0.90, 0.84; MS (El) mlz 389 (M + ), 333, 316, 298, 277, 243, 242, 202, 105, 104, 57. Step 2. Preparation of tert-Butyl α-(l-Hydroxymethyl)-3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrrolidineacetate (αR-diastereomer). A cold (-78 °C) solution of oxalyl chloride (1.02 mL, 11.7 mmol) in dry CHgClg (30 mL) is treated with DMSO (1.66 mL, 23.4 mmol, in 5 mL CH 2 C1 2 ). After 5 min, tert-butyl α-( l-hydroxymethyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3- pyrroUdineacetate (S-isomer) (3.80 g, 9.76 mmol) is added. The solution is stirred for an additional 15 min and then quenched with triethylamine (6.8 mL, 48.8 mmol). The solution is maintained at -78 °C for 30 min and then aUowed to warm to room temperature under N 2 . After 2.5 hours, the solution is dUuted with H 2 0 (50 mL) and extracted into EtOAc (3 X 100 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide a quantitative yield of the desired aldehyde as a ca. 1:2 mixture in favor of the R diastereomer. Key peaks of the NMR of the crude mixture: 1H NMR (300 MHz, CDC1 3 ) δ 9.75, 9.48. A cold (0 °C) solution of the aldehyde mixture (1.68 g, 4.34 mmol) in MeOH (30 mL) is treated with sodium borohydride (246 mg, 6.51 mmol). The solution is maintained at 0 °C for 1 h, and then allowed to warm to room temperature. After 3 hours, the solution is concentrated to a yeUow foam. The foam is diluted with H 2 0 (25 mL) and extracted with EtOAc (3 X 50 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure. The material, 1.69 g, is purified by silica gel chromatography (100 g SG; 20% EtOAc hexane) to provide 562 mg (33%) of the title compound, 467 mg (28%) of the S diastereomer and 331 mg of the unreduced aldehyde. Spectral data for the title compound: IR (mineral oU) 3542, 3006, 1704, 1672, 1499, 1396, 1313, 1265, 1160, 1124, 1066, 1059, 1036, 738, 697 cm "1 ; 1 H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.95, 3.75, 3.60-3.75, 3.40-3.65, 3.24, 2.87, 2.69, 1.80-2.15, 1.40-1.70, 1.45, 0.89, 0.87; MS (FAB) m/z 390 (MH + ), 335, 334, 332, 316, 298, 242, 105, 57. Step 3. Preparation of tert-Butyl α-(l-Azidomethyl)-3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrrolidineacetate. Methanesulfonyl chloride (0.058 mL, 0.751 mmol) is added dropwise to a solution of tert-butyl α-(l-hydroxymethyl)-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)- 3-pyrrolidineacetate (αR-diastereomer) (225 mg, 0.578 mmol) and triethylamine (105 mL, 0.751 mmol) in dry CH 2 C1 2 (3 mL). The solution is stirred overnight at room temperature under N 2 . After dUuting with CH^l^ (20 mL), the solution is washed with saturated NaHCOg (5 mL), H 2 0 (5 mL), and brine (5 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 289 mg of a gold ofl. The oU is purified by siUca gel chromatography (10 g SG; 20% EtOAc/hexane) to provide 243 mg (90%) of the mesylate as an oU: 1H NMR (300 MHz, CDClg) δ 7.10-7.40, 4.47, 4.17, 3.35-3.70, 3.05-3.30, 2.90-3.05, 2.97, 2.84, 2.10-2.30, 1.75-1.95, 1.30-1.70, 1.46, 0.88, 0.86. A solution of the mesylate (795 mg, 1.70 mmol) and sodium azide (166 mg, 2.55 mmol) in DMSO (6 mL) is heated at 60 °C for 24 hours and then aUowed to cool to room temperature under N 2 . The solution is diluted with Et j O (40 mL) and washed with H^O (3 X 15 mL) and brine (15 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 679 mg (96%) of the title compound as a clear, colorless oU: IR (liq.) 2958, 2932, 2870, 2101, 1725, 1682, 1498, 1455, 1393, 1368, 1276, 1152, 1122, 748, 700 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.10-3.80, 3.00, 2.70-2.95, 2.15-2.30, 1.30- 1.90, 1.47, 0.85; MS (El) mlz 414 (M + ), 358, 268, 267, 246, 224, 212, 105, 104, 57. Step 4. Preparation of tert-Butyl α-(l-Aminomethyl)-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate. A mixture of tert-butyl α-(l-azidomethyl)-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate (648 mg, 1.56 mmol) and 10% paUadium on carbon (163 mg) in EtOH (25 mL) is hydrogenated at 30 psi in a Parr flask for 16 hours. The mixture is filtered, rinsing the residual soUds with MeOH and CH 2 C1 2 . The filtrate is concentrated and purified by silica gel chromatography (15 g SG; EtOAc, 15% MeOH EtOAc) to provide 356 mg (57%) of the title compound as a partiaUy crystalline soUd: IR (mull) 3004, 1718, 1672, 1498, 1394, 1311, 1296, 1263, 1223, 1156, 1149, 852, 738, 697, 620 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 3.35-3.70, 3.05-3.30, 2.70-2.95, 2.60-2.70, 2.45-2.60, 2.20-2.40, 1.25-2.00, 1.46, 0.85 MS (FAB) mlz 389 (MH + ), 359, 334, 333, 316, 202, 105, 57. Step 5. Preparation of tert-Butyl α-[[[(4- Methoxyphenyl ) sulfonyl]amino]methyl]-3-(2-methylpropyl ) -2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate . A cold (0 °C) solution of tert-butyl α-(l-aminomethyl)-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrrolidineacetate (337 mg, 0.867 mmol) in dry CH 2 C1 2 (3 mL) is treated with dusopropylethylamine (240 μL, 1.30 mmol) and 4- methoxybenzenesulfbnyl chloride (215 mg, 1.30 mmol). The solution was allowed to slowly warm to room temperature, stirring overnight under N 2 . After dUuting with CH 2 C1 2 (25 mL), the solution is washed with dilute NaHCOg (10 mL), H 2 0 (10 mL), and brine (10 mL). The organic layer was dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 460 mg of a yeUow oU. The oU was purified by silica gel chromatography (20 g SG; 25% EtOAc/hexane) to provide 383 mg (79%) of the desired material as a white amorphous soUd: IR (liq.) 2958, 2932, 1725, 1668, 1598, 1499, 1455, 1444, 1368, 1334, 1304, 1279, 1260, 1160, 1097 cm "1 ; X H NMR (300 MHz, CDC1 3 ) δ 7.79, 7.10-7.35, 6.95, 5.45-5.60, 3.81, 3.30-3.65, 2.95- 3.30, 2.60-2.90, 2.00-2.20, 1.70-1.90, 1.20-1.70, 1.43, 0.80; MS (El) mlz 558 (M + ), 411, 387, 287, 246, 245, 202, 171, 107, 105, 57. Step 6. Preparation of α-[[[(4-Methoxyphenyl)sulfonyl]amino]methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid. A cold (0 °C) solution of tert-butyl α-[[[(4-methoxyphenyl)sulfbnyl] amino]methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrrolidineacetate (374 mg, 0.669 mmol) in CH^L^ (2 mL) is treated with TFA (2 mL). The solution is maintained at 0 °C for 40 min and then allowed to warm to room temperature under N 2 . After 1.5 hours, the solution is diluted with CH 2 C1 2 and stripped (5 X). The residual foam is dfluted with H 2 0 (5 mL) and extracted into CH 2 C1 2 (3 X 20 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide 301 mg (90%) of the title compound as a white, amorphous soUd: IR (mull) 3062, 3026, 1713, 1647, 1597, 1580, 1498, 1332, 1304, 1261, 1180, 1158, 1096, 834, 701 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.70-7.80, 7.15-7.35, 6.90-7.00, 5.45-5.55, 3.86, 3.45- 3.75, 3.00-3.40, 2.89, 2.67, 1.95-2.25, 1.35-1.60, 0.84, 0.78; MS (El) mlz 502 (M + ), 411, 287, 246, 245, 244, 202, 171, 107, 105, 77. Step 7. Preparation of iV-Benzyloxy-α-[t[(4-methoxyphenyl)sulfonyl]amino] methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. A solution of α-[[[(4-methoxyphenyl)sulfonyl]amino]methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid (290 mg, 0.577 mmol) in dry CH 2 C1 2 (5 mL) is treated with CDI (112 mg, 0.692 mmol). After 1 h, 4- methylmorphoUne (0.095 mL, 0.866 mmol) and 0-benzylhydroxyamine HCl (138 mg, 0.866 mmol) are added. The solution is stirred at room temperature under N 2 for 65 h. The solvent had evaporated, and the residual gel is dUuted with EtOAc (25 mL). The solution is washed with 1 N HCl (10 mL), 1 N NaOH (10 mL), and brine (10 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 380 mg of an oU. The oU is purified by siUca gel chromatography (30 g SG; 50% EtOAc/hexane) to provide 249 mg (71%) of the title compound as an oil: IR (mull) 3205, 3028, 1658, 1597, 1498, 1331, 1304, 1287, 1261, 1157, 1096, 1027, 834, 749, 699 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.70-7.85, 7.10-7.45, 6.85-7.00, 5.70-5.80, 4.86, 3.76, 3.40-3.55, 3.00-3.25, 2.60-3.00, 2.30-2.50, 1.80-2.00, 1.30-1.60, 0.82, 0.75; MS (FAB) mlz 608 (MH + ), 485, 298, 286, 244, 171, 107, 105, 91. Step 8. Preparation of N-Hydroxy-α-[[[(4- methoxyphenyl)sulfonyl]amino]methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide. A solution of N-benzyloxy-α-[[[(4-methoxyphenyl)sulfonyl]amino]methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (218 mg, 0.359 mmol) in EtOH (7 mL) is treated with paUadium hydroxide on carbon (55 mg) and placed under a H 2 atmosphere via a baUoon. After 6.5 hours, the mixture is filtered, rinsing the residual soUds with MeOH and CHClg. The filtrate is concentrated to give 182 mg of a white solid. The material is crystalUzed from hot EtOAc with a trace of MeOH, eventuaUy dUuting with hexane, to provide 136 mg of the title compound as a soUd (mp 195-196 °C): IR (mull) 3317, 3095, 1658, 1620, 1597, 1496, 1335, 1304, 1257, 1163, 1097, 833, 829, 805, 751 cm '1 ; X H NMR (300 MHz, CDClg) δ 7.78, 7.05-7.35, 6.91, 6.20-6.35, 3.75, 3.35-3.60, 3.05- 3.35, 2.60-2.90, 2.25-2.50, 1.80-2.00, 1.15-1.70, 0.83, 0.77; MS (El) mlz 517 (M + ), 261, 245, 244, 202, 171, 154, 107, 105. EXAMPLE 91 Preparation of N-Hydroxy-α-[[t(4- methoxyphenyl)sulfonyl]amino]methyl]-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide (αS-diastereomer). mp 60-64 °C); NMR (300 MHz, CDClg) δ 7.70-7.90, 7.10-7.40, 6.85-7.05, 5.40-5.60, 3.86, 3.40- 3.60, 2.95-3.30, 2.70-2.85, 2.05-2.25, 1.30-1.90, 0.65-0.90. EXAMPLE 92 Preparation of α-[[(4-Fluorophenyl)sulfonyl]amino]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylet-hyl)-3-pyrroUdineacetamide (R-diastereomer). Step 1. Preparation of tert-Butyl α-Azido-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate (αR-diastereomer). Potassium bis(trimethylsilyl)amide (0.5 M in toluene, 19.9 mL, 9.93 mmol) is added to a solution of tert-butyl 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (EXAMPLE 1, step 3; 1.70 g, 4.73 mmol) and THF (57 mL) at -78 C C. The solution is aUowed to stir at -78 °C for 25 min. A solution of trisylazide (3.66 g, 11.8 mmol) in THF (34.5 L) is added dropwise over 5 min. The solution is stirred for an additional 2 min and acetic acid (1.2 mL) is added. The solution was aUowed to warm slowly and stir at room temperature overnight. Aqueous workup (EtOAc. NaHCOg wash, brine wash, MgS0 4 ) and column chromatography (7.5 % EtOAc/hexane) provides 1.34 g (71%) of the title compound as a yeUow oU: 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 4.23, 4.12, 3.65-3.80, 3.50-3.65, 3.15-3.40, 2.75-2.90, 2.35-2.50, 2.10-2.30, 1.15-1.85, 0.75-0.95; MS (ESI) 401 (MH + ). Step 2. Preparation of tert-Butyl α-Amino-3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdineacetate (αR-diastereomer). A mixture of tert-butyl α-azido-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetate (159 mg, 0.397 mmol), paUadium on carbon (10%, 40 mg) and EtOH (2.0 mL) is hydrogenated overnight at 30 psi. The mixture is filtered and concentrated to give 145 mg (97%) of the title compound as an oil: X H NMR (300 MHz, CDClg) δ 7.15-7.39, 3.55-3.75, 3.15-3.35, 2.84, 2.15-2.30, 1.85- 1.95, 1.30-1.80, 1.46, 0.89, 0.84; MS (ESI) 375 (MH + ). FoUowing the procedures outUned in EXAMPLE 90 (steps 5-8) and making non- critical modifications, but starting with tert-butyl α-amino-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetate (αR-diastereomer), the title compound is obtained (mp 111-113 °C): 1H NMR (300 MHz, CDClg) δ 9.05, 7.80-7.90, 7.05-7.35, 6.85, 5.25-5.50, 4.50-4.60, 3.80-3.90, 3.60-3.75, 3.05-3.60, 2.70-2.85, 2.10-2.35, 1.40-1.90, 1.55, 0.70-0.90; MS (ESI) 492 (MH + ). Following the general procedures outlined in EXAMPLE 92 and making non- critical variations, the following compounds were prepared. EXAMPLE 93 Preparation of α-[[(4-Fluorophenyl)sulfonyl]amino]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αS-diastereomer). mp 99-102 °C; NMR (300 MHz, CDClg) δ 7.75-7.85, 7.10-7.35, 5.06, 3.45-3.60, 3.15-3.35, 2.85, 2.35-2.50, 1.95-2.10, 1.15-1.60, 0.78, 0.74; MS (ESI) 492 (MH + ). EXAMPLE 94 Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-iV- hydroxy-3-(3-hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. Step 1. Preparation of tert-Butyl α-(2-Chloroethyl)-2-oxo-l-(2-phenylethyl)-3- (propen-2-yl)-3-pyrroUdineacetate A cold (-78 °C) solution of tert-butyl 2-oxo-l-(2-phenylethyl)-3-(propen-2-yl)-3- pyrrolidineacetate (prepared similarly to that described in EXAMPLE 1, step 3; 5.52 g, 16.1 mmol) in dry THF (100 mL) is treated with the dropwise addition of LDA (9.66 mL, 19.3 mmol, 2.0 N). The solution is stirred for 30 min, and then treated with the dropwise addition of l-bromo-2-chloroethane (1.61 mL, 19.3 mmol). The solution is maintained at -78°C for 5 hours and then aUowed to slowly warm to room temperature under N 2 overnight. The solution is quenched with saturated NH 4 C1 (10 mL) and dUuted with H 2 0 (25 mL). The product is extracted with EtOAc (3 X 100 mL), dried over anhydrous MgS0 4 , filtered, and concentrated to give 6.6 g of a brown oil. The oil is purified by silica gel chromatography (275 g SG; 10% EtOAc/hexane) to provide 5.07 g (78%) of the title compound as a clear, yeUow oil: IR (liq.) 2977, 2931, 1721, 1685, 1496, 1455, 1440, 1393, 1367, 1282, 1257, 1149, 917, 748, 701 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.15-7.35, 5.45-5.65, 4.95-5.15, 3.25-3.80, 3.05-3.25, 2.81, 2.71, 1.90-2.45, 1.65-1.85, 1.43; MS (El) mlz 405 (M + ), 370, 351, 349, 332, 314, 260, 259, 258, 105, 104, 57. Step 2. Preparation of tert-Butyl α-(2-Azidoethyl)-2-oxo-l-(2-phenylethyl)-3- (propen-2-yl)-3-pyrroUdineacetate A solution of tert-butyl α-(2-chloroethyl)-2-oxo-l-(2-phenylethyl)-3-(propen-2- yl)-3-pyrroUdineacetate (2.10 g, 5.17 mmol) in DMSO (15 mL) is treated with sodium azide (504 mg, 7.74 mmol). The mixture is heated to 60 °C (oU bath) for 17 hours. The resultant solution was cooled to room temperature, dUuted with Et^O (100 mL), washed with H 2 0 (3 X 50 mL) and brine (50 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide a quantitative yield of the title compound as a yeUow oil: hi NMR (300 MHz, CDClg) δ 7.15-7.35, 5.40-5.65, 4.95-5.15, 3.60-3.80, 3.05-3.40, 2.81, 2.60, 2.10-2.40, 1.65-2.05, 1.43. Step 3. Preparation of tert-Butyl α-(2-Aminoethyl)-2-oxo-l-(2-phenylethyl)-3- (propen-2-yl)-3-pyrroUdineacetate. A solution of tert-butyl α-(2-azidoethyl)-2-oxo-l-(2-phenylethyl)-3-(propen-2- yl)-3-pyrroUdineacetate (2.12 g, 5.14 mmol) and triphenylphosphine (1.48 g, 5.65 mmol) in THF (15 mL) is stirred under N 2 for 7 hours. Water (1 mL) is added and the solution stirred overnight at room temperature under N 2 . The solution is concentrated and purified by siUca gel chromatography (75 g SG; EtOAc, 20% MeOH/EtOAc) to provide 1.94 g (97%) of the title compound as a yeUow oU: 2 H NMR (300 MHz, CDClg) δ 7.15-7.35, 5.45-5.65, 4.95-5.15, 3.60-3.80, 3.05-3.40, 2.80, 2.50-2.80, 2.10-2.45, 1.60-1.90, 1.42. Step 4. Preparation of tert-Butyl α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-2-oxo- l-(2-phenylethyl)-3-(propen-2-yl)-3-pyrroUdineacetate A cold (0 C C) solution of tert-butyl α-(2-aminoethyl)-2-oxo-l-(2-phenylethyl)-3- (propen-2-yl)-3-pyrroUdineacetate (1.93 g, 4.99 mmol) in dry CH 2 C1 2 (20 L) is treated with dusopropylethylamine (1.04 mL, 5.99 mmol) and 3,4-difiuorobenzoyl chloride (691 μL, 5.49 mmol). The solution is aUowed to warm to room temperature, stirring under N 2 overnight. The solution is diluted with EtOAc (100 mL) and washed with 1 N HCl (25 mL), 1 N NaOH (25 L), and brine (25 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 3.60 g of a brown oil. The oil is purified by siUca gel chromatography (50 g SG; 25% EtOAc/hexane) to provide 2.10 g (80%) of the title compound as a yeUow, amorphous soUd: m (mineral oU) 3360, 1717, 1660, 1606, 1550, 1509, 1497, 1436, 1315, 1295, 1281, 1199, 1154, 831, 775 cm "1 ; λ Η. NMR (300 MHz, CDClg) δ 7.65-7.75, 7.50-7.60, 7.15-7.35, 6.70, 5.45-5.65, 4.90- 5.10, 3.55-3.85, 3.10-3.45, 2.70-2.90, 2.62, 2.10-2.35, 1.65-1.90, 1.43; MS (ESI) mlz 549 (MNa + ). Step 5. Preparation of tert-Butyl α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate. A cold (0 °C) solution of tert-butyl α-[2-[(3,4-difluorobenzoyl)arnino]ethyl]-2- oxo-l-(2-phenylethyl)-3-(propen-2-yl)-3-pyrroUdineacetate (1.62 g, 3.07 mmol) in dry THF (10 mL) is treated with monochloroborane methylsulfide complex (640 μL, 6.14 mmol). The ice bath is removed, and after 4.5 h, 3 N NaOH (7.4 mL, 22.1 mmol) is added dropwise, followed by 30% H 2 0 2 (2.5 mL). The solution is stirred for 1 hour at room temperature and then for 1 hour at 50 °C. After cooling to room temperature and dUution with saturated NH C1 (5 mL) and H 2 0 (15 mL), the product is extracted into EtOAc (3 X 50 mL). The extracts are combined, dried over anhydrous MgS0 , filtered, and concentrated under reduced pressure to give 1.6 g of a yellow gel. The material is purified by siUca gel chromatography (75 g SG; 75% EtOAc/hexane) to provide 713 mg (43%) of the title compound as a white, amorphous solid: IR (liq.) 3335, 2934, 1721, 1666, 1606, 1554, 1511, 1455, 1368, 1316, 1296, 1283, 1250, 1204, 1153 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.65-7.75, 7.45-7.60, 7.15-7.35, 6.60-6.75, 3.75-3.95, 3.10-3.70, 2.70-2.90, 2.65, 2.20-2.40, 2.00-2.20, 1.42, 1.05-1.90; MS (ESI) m lz 567 (MNa + ). Step 6. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetic acid. A cold (0°C) solution of tert-butyl α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetate (655 mg, 1.20 mmol) in CHgC^ (3 mL) is treated with TFA (2 mL) and maintained at 0°C for 30 min. The ice bath is removed, and after 2 hours, the solution is diluted with CH 2 C1 2 and concentrated (3 X). The residual oU is diluted with H 2 O (10 mL) and extracted into CH 2 C1 2 (3 X 50 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide a quantitative yield of the title compound as a white, amorphous soUd: IR (liq.) 1785, 1724, 1644, 1619, 1605, 1557, 1511, 1455, 1442, 1322, 1297, 1284, 1207, 1171, 701 cm "1 ; NMR (300 MHz, CDClg) δ 7.60-7.75, 7.50-7.60, 7.15-7.40, 6.85-7.00, 4.10-4.35, 3.50-3.80, 3.20-3.45, 2.80-3.00, 2.54, 1.20-2.00; MS (El) mlz 488, 470, 397, 379, 260, 246, 141, 113. Step 7. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-benzyloxy-3- (3-hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. A cold (0 °C) solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-3-(3- hydroxypropyl)-2-oxo-l-(2-phenyletnyl)-3-pyrroUdineacetic acid (586 mg, 1.20 mmol) in 2:1 (7.5 mL) is treated with HOBT (195 mg, 1.44 mmol), EDC (276 mg, 1.44 mmol), and 4-methylmorphoUne (158 μL, 1.44 mmol). The ice bath is removed, and after 1 hour, 0-benzymydroxylamine HCl (287 mg, 1.80 mmol) and a second portion of 4-methylmorpholine (198 μL, 1.80 mmol) are added. The solution is stirred overnight at room temperature under N 2 . The solution is dUuted with H 2 0 (25 mL) and extracted into CH 2 C1 2 (3 X 50 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide an oil. The residual oU is reconstituted in EtOAc (50 mL) and washed with 1 N HCl (10 mL), 1 N NaOH (10 mL), H 2 0 (10 mL), and brine (10 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 603 mg of a white foam. The material is purified by siUca gel chromatography (25 g SG; EtOAc) to provide 433 mg (62%) of the title compound as a white, amorphous soUd: I (liq.) 3328, 2941, 1664, 1619, 1605, 1554, 1511, 1454, 1438, 1319, 1298, 1283, 1205, 750, 700 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.60-7.75, 7.45-7.60, 7.10-7.45, 6.75-6.85, 4.86, 3.35- 3.70, 3.10-3.30, 2.75-2.90, 2.30-2.45, 1.10-2.15; MS (FAB) mlz 594 (MH + ), 593, 592, 531, 489, 472, 471, 453, 313, 57. Step 8. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. A solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-N-benzyloxy-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (215 mg, 0.368 mmol) is dissolved in EtOH (5 mL) and purged with N 2 . Pearlman's catalyst (22 mg) is added and the atmosphere was replaced with H 2 . After 7 hours, the mixture is filtered through celite, washing the residual soUds with MeOH, EtOH, and CH 2 C1 2 . The filtrate is concentrated to give 171 mg of a sUghtly brown foam. The material is crystalUzed from hot EtOAc (dUuting with hexane). The product is isolated and dried in the vacuum oven (45 °C) overnight to provide 117 mg (63%) of the title compound as a cream-colored, powdery soUd (mp 118 °C, dec): IR (mineral oU) 3274, 3225, 3064, 3027, 1656, 1620, 1606, 1559, 1512, 1359, 1319, 1290, 1282, 1060, 701 cm "1 ; 1H NMR (300 MHz, CDC1 3 ) δ 7.45-7.80, 7.10-7.40, 3.10-3.75, 2.70-2.90, 2.40-2.60, 1.15-2.25; MS (FAB) mlz 504 (MH + ), 503, 502, 488, 471, 313, 246, 141, 105. EXAMPLE 95 Preparation of a-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-iV- hydroxy-3-(2-hydroxyethyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. Step 1. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-2-oxo-l-(2- phenylethyl)-3-(propen-2-yl)-3-pyrroudineacetic acid A cold (0 °C) solution of tert-butyl α-t2-t(3,4-difluorobenzoyl)amino]ethyl]-2- oxo-l-(2-phenylethyl)-3-(propen-2-yl)-3-pyrroUdineacetate (EXAMPLE 94, step 4; 505 mg, 0.959 mmol) in CH 2 C1 2 (2 mL) is treated with TFA (2 mL) and maintained at 0 °C for 30 min. The ice bath is removed, and after 1 h, the solution was diluted with CH 2 Cl2 and concentrated (3 X). The residual oil is diluted with H 2 0 (10 L) and extracted into CH 2 C1 2 (3 X 25 mL). The extracts are combined, dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to provide 430 mg (95%) of the title compound as a slightly yeUow, amorphous soUd: (liq.) 1727, 1662, 1641, 1619, 1606, 1554, 1510, 1454, 1441, 1316, 1298, 1283, 1203, 775, 700 cm "1 ; 2 H NMR (300 MHz, CDClg) δ 7.60-7.75, 7.50-7.60, 7.15-7.40, 6.75-6.90, 5.45-5.65, 5.10-5.20, 3.50-3.75, 3.15-3.35, 2.88, 2.52, 2.34, 1.70-2.05, 1.20-1.45; MS (ESI) mlz 469 (M " ). Step 2. Preparation of α-[2-[(3,4-Dϋluorobenzoyl)amino]ethyl]-iv " -benzyloxy-2- oxo-l-(2-phenylethyl)-3-(propen-2-yl)-3-pyrroUdineacetamide. A cold (0 °C) solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-2-oxo-l-(2- phenylethyl)-3-(propen-2-yl)-3-pyrroUdineacetic acid (427 mg, 0.908 mmol) in 2:1 CHgCL DMF (6 mL) is treated with HOBT (147 mg, 1.09 mmol), EDC (209 mg, 1.09 mmol), and 4-methylmorpholine (120 μL, 1.09 mmol). The ice bath is removed, and after 1 hour, a second portion of 4-methylmorphoUne (150 μL, 1.36 mmol) and O- benzylhydroxylamine HCl (217 mg, 1.36 mmol) are added. The solution is stirred overnight at room temperature under N 2 . The solution is dUuted with EtOAc (25 mL) and washed with 1 N HCl (10 mL), 1 N NaOH (10 mL), H 2 0 (2 X 10 mL), and brine (10 mL). The organic layer is dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 530 mg of a yeUow soUd. The soUd is purified by sUica gel chromatography (30 g SG; 50% EtOAc hexane) to provide 373 mg (71%) of the title compound as a white, amorphous soUd: IR (mineral oil) 3336, 3193, 1679, 1669, 1641, 1608, 1544, 1509, 1495, 1442, 1311, 1296, 1275, 747, 696 cm "1 ; X H NMR (300 MHz, CDClg) δ 7.05-7.75, 6.65-6.85, 5.40-5.60, 4.80-5.15, 3.35-3.70, 3.05-3.30, 2.81, 1.35-2.45; MS (ESI) mlz 574 (M " ). Step 3. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-benzyloxy-3- (2-hydroxyetnyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. α-[2-[ ( 3,4-Difluorobenzoyl ) amino]ethyl]-iV-benzyloxy-2-oxo-l-(2-phenylethyl)-3- (propen-2-yl)-3-pyrroUdineacetamide (365 mg, 0.634 mmol) is dissolved in warm EtOH (10 mL) and cooled to -78 °C. The solution is subjected to ozone for 3.5 min and then purged with N 2 for 15 min. The ozonide is quenched with NaBH (36 mg, 0.951 mmol) and allowed to slowly warm to room temperature under N 2 . After 5 hours, additional NaBH 4 (36 mg, 0.951 mmol) is added and the mixture allowed to stir overnight. The mixture is concentrated, diluted with H 2 0 (20 mL) and extracted into EtOAc (3 X 50 mL). The extracts are dried over anhydrous MgS0 4 , filtered, and concentrated under reduced pressure to give 306 mg of a white foam. The foam is purified by siUca gel chromatography (25 g SG; EtOAc) to provide 123 mg (34%) of the title compound as a white, amorphous soUd: IR (mineral oU) 3321, 1664, 1619, 1605, 1554, 1510, 1318, 1297, 1283, 1205, 1028, 776, 750, 699, 626 cm "1 ; 1H NMR (300 MHz, CDClg) δ 7.10-7.75, 6.65-6.75, 4.85, 3.10-3.70, 2.70-2.90, 2.45- 2.60, 2.10-2.30, 1.50-1.95; MS (ESI) mlz 580 (M + ), 578 (M). Step 4. Preparation of α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-iV-hydroxy-3-(2- hydroxyethyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. A solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-N-benzyloxy-3-(2- hydroxyethyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (117 mg, 0.202 mmol) is dissolved in EtOH (3 mL) and purged with N 2 . Pearlman's catalyst (10 mg) is added and the atmosphere is replaced with H 2 . After 6 hours, the mixture is filtered through ceUte, washing the residual solids with MeOH, EtOH, and CH 2 C1 2 . The filtrate is concentrated and resubjected to the same procedure. The recovered material (99 mg) is purified by silica gel chromatography (8 g SG; 5, 10% MeOH/CHClg) to give 45 mg of a white, amorphous soUd. The solid is triturated with Et 2 0/hexane, filtered, and dried. This provides 39 mg (40%) of the title compound as a white, powdery soUd (mp 135-137 °C): IR (mineral oU) 3202, 3089, 3063, 3029, 1670, 1648, 1633, 1601, 1564, 1515, 1499, 1435, 1331, 1320, 1299 cm *1 ; l R NMR (300 MHz, DMSO-dg) δ 8.77, 8.40-8.55, 7.80-7.90, 7.65-7.75, 7.45-7.60, 7.10-7.30, 4.30-4.40, 3.00-3.50, 2.60-2.75, 2.10-2.45, 1.50-1.90; MS (FAB) mlz 490 (MH + ), 489, 474, 457, 439, 299, 246, 141, 105. EXAMPLE 96 Preparation of [R-(R*,S*)]-α-[2-[(3-Fluorobenzoyl)amino]ethyl]- N-hydroxy-3-(3-hydroxypropyl)-2-oxo-l-(2-phenyletnyl)-3-pyrroUdineacetamide. [α] D 25 = +13° (c 0.71, CHC1 3 ); IR (mineral oU) 3233, 3085, 3064, 3026, 1662, 1586, 1547, 1497, 1484, 1319, 1299, 1271, 1225, 751, 701 cm "1 ; 4l NMR (300 MHz, CDClg) δ 7.45-7.60, 7.05-7.45, 3.10-3.65, 2.70-2.90, 2.45-2.60, 1.15-2.25; MS (El) mlz 485 (M + ), 248, 247, 202, 178, 156, 123, 105, 104, 95, 56. FoUowing the general procedures outUned in EXAMPLES 28-29 or 30-34 and making non-critical variations, the foUowing compounds may be prepared. EXAMPLE 97 Preparation of [S-( β *Ji*)3-iV 3 -hydroxy-N 1 -methyl-α 1 -(l- methylethyl)-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 98 Preparation of [S-(- " ?*J**)j--V 1 -cyclopropyl-Λ "3 -hydroxy-α 1 -(l- methylethyl)-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 99 Preparation of [S-(J?*Ji*)]-iV 3 -hydroxy-α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 100 Preparation of [S-(β*-R*)]-N 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 - ( l-methylethyl)-3-(2-methylpropyl)-2-oxo- 1,3-pyrroUdinediacetamide. EXAMPLE 101 Preparation of [S<R* J! » )]-W 3 -hydrox -α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-W 1 ^4-pyridinyl)-l,3-pyrrou^nediacetainide. EXAMPLE 102 Preparation of [S-(ie*Jt*)]-α 1 -.ert-butyl-N 1 -cyclopropyl-N 3 - hyclroxy-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 103 Preparation of [S-(/e*J2*)]-α 1 -tert-butyl-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-N -phenyl- 1,3-pyrroUdinediacetamide. EXAMPLE 104 Preparation of [S-(i?*J?*)]-α 1 -fert-butyl-N 1 -(4-fluorophenyl)-iV 3 - hyorcory-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 105 Preparation of [S-CR*,β*)]-α 1 -Cert-butyl-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 106 Preparation of [S-(i2*J2*)]-α 1 -cyclohexyl-iV 3 -hydroxy-3-(2- methylpropyl)-2-oxo-JV 1 -phenyl- 1 ,3-pyrroUdinediacetamide. H EXAMPLE 107 Preparation of [S-(-S* R*)]-α 1 -cyclohexyl-N 3 -hydroxy-3-(2- metnylpropyl)-2-oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 108 Preparation of [S-(i2*J2*)]-3-(cyclopentylmethyl)-N 3 -hydroxy- N 1 -methyl-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 109 Preparation of [S-(i2*J2*)]-3-(cyclopentylmethyl)-N 1 -cyclopropyl- N^-hydroxy-α -( l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 110 Preparation of [5-( J R*J?*)]-3-(cyclopentylmethyl)-N 3 -hydroxy-α 1 - ( l-methylethyl)-2-oxo-iV -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 111 Preparation of [S-(i2*J?*)]-3-(cyclopentylmethyl)-N 1 -(4- fluorophenyl)-N -hydroxy-α 1 -(l-metnylet-hyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 112 Preparation of [S-^^JJ^l-S^cyclopentylmethyD-iv^-hydroxy-α 1 - (l-methylethyl)-2-oxo-N 1 -(4-pyridmyl)-l,3-pvrroUd ediacetamide. EXAMPLE 113 Preparation of [S-(fl*J?*)]-α 1 -fert-butyl-3-(cyclopentylmethyD- N 3 -hydroxy-N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 114 Preparation of [S-(i2*^*)]-α 1 -tert-butyl-3-(cyclopentylmethyD- N 1 -cyclopropyl-iV 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 115 Preparation of [S-(iϊ*J?*)]-α 1 -^rt-butyl-3-(cyclopentylmethyl)- iV^-hydroxy-2-oxo-N -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 116 Preparation of [S-(i2*- β *)]-α 1 -tert-butyl-3-(cyclopentylmethyl)- iV 1 -(4-fluorophenyl)-iv ' ^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 117 Preparation of [S-(i2*JΪ*)3-α 1 -tert-butyl-3-(cyclopentylmethyl)- N 3 -hydroxy-2-oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 118 Preparation of tS-(ie*J?*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)- Λ^-hydroxy-N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 119 Preparation of [S-(i2*-R*)]-α 1 -cyclohexyl-3-(cyclopentylmethyD- N 1 -cyclopropyl--^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 120 Preparation of [S-(Λ*J?*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)- N 3 -hydroxy-2-oxo-JV -phenyl- 1,3-ρyrrolidinediacetamide. EXAMPLE 121 Preparation of [S-(Λ*J?*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)- N -(4-fluorophenyl)-iV^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 122 Preparation of t5-(i?*J2*)]-a 1 -cyclohexyl-3-(cyclopentylmethyl)- Λ^-hydroxy-2-oxc-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. 97/32846 EXAMPLE 123 Preparation of [S-(β*-R*)]-N 3 -hydroxy-N 1 -methyl-α 1 - ( l- me ( thylethyl)-2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 124 Preparation of [S-(R* J?* )]-N 1 -cyclopropyl-N 3 -hydroxy-α x - ( 1- methylethyl ) -2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 125 Preparation of [S-(i?*J2*)]-N 3 -hydroxy-α 1 - ( l-methylethyl ) -2-oxo- 1 -phenyl-3- ( 3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 126 Preparation of [S-( β *J?*)]-Λ/ '1 -(4-fluorophenyl)-iV 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 127 Preparation of [S-(ie*J2*)]-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo- 3-(3-phenylpropyl)-2V -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 128 Preparation of [S-(Λ*-R*)]-α 1 -tert-butyl-N 3 -hydroxy-N 1 -methyl- 2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. 97/32846 EXAMPLE 129 Preparation of [S-^^^l-α^ert-butyl-^-cyclopropyl-N 3 - hydroxy-2-oxo-3- ( 3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 130 Preparation of [S-(R*Jl* )]-α 1 -tert-butyl-N 3 -hydroxy-2-oxo-iV 1 - phenyl-3- ( 3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 131 Preparation of [S-^^^l-α^tert-butyl-N^^fluorophenyD-N 3 hydroxy-2-oxo-3- ( 3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 132 Preparation of [S-(i2*-ff*)]-α 1 -tert-butyl-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 133 Preparation of [S-(R*β*)]- 1 -cyclohexyI-N θ -hydroxy-N 1 -methyl- 2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 134 Preparation of [5-(β*J?*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-iv *3 - hydroxy-2-oxo-3-(3-phenylpropyl)-l,3-ρyrroUdinediacetamide. EXAMPLE 135 Preparation of [S-(Λ*Ji*)]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo-N 1 - phenyl-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 136 Preparation of [S-(22*-K*)]-α 1 -cyclohexyl-iV 1 -(4-fluorophenyl)-JV 3 - hydroxy-2-oxo-3-(3-phenylpropyl)-l,3-pyrroUdinediacetamide. EXAMPLE 137 Preparation of tS-(β*-R*)]-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 138 Preparation of [S-(β*,fl*)j-3-[3-(4-fluorophenyl)propyl]-_V 3 - hydroxy-N 1 -methyl-α 1 -( l-methylethyl)-2-oxo- 1,3-pyrroUdinediacetamide. EXAMPLE 139 Preparation of [S-(R* J?*)]-iV 1 -cyclopropyl-3-[3-(4- fluorophenyl)propyl]-Λ^-hydroxy-α -(l-methylethyl)-2-oxo-l,3- pyrroUdinediacetamide. EXAMPLE 140 Preparation of [S-(ie*J**)]-3-[3-(4-fluorophenyl)propyl]-_V 3 - hydroxy-α 1 -( l-methylethyl)-2-oxo-N 1 -phenyl- 1 ,3-pyrroUdinediacetamide. EXAMPLE 141 Preparation of [S-CR*-R* )]-N 1 -(4-fluorophenyl)-3-[3-(4- fluorophenyDpropyU-iv^-hydroxy-α 1 -( l-methylethyl)-2-oxo- 1,3- pyrroUdinediacetamide. EXAMPLE 142 Preparation of [S-(i?*J2*)]-3-t3-(4-fluorophenyl)propyl]-N 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-ΛT -(4-pyridinyl)-l,3-pyrrolidinediacetamide. EXAMPLE 143 Preparation of [S-lR*-R*)]-a 1 -tert-butyl-3-[3-(4- fluorophenyl)propyl]-N 3 -hydroxy-N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 144 Preparation of [S-( β *J?*)]-α 1 -tert-butyl-N 1 -cyclopropyl-3-[3-(4- fluorophenyl)propyl]-N 3 -hydroxy--2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 145 Preparation of [S-(R*β*)]- ^tert-butyl-S-tø-^- fluorophenyl )propyl]-iV -hydroxy-2-oxo-iV 1 -phenyl- 1 , 3-pyrroUdinediacetamide. EXAMPLE 146 Preparation of [S-(iϋ*J2*)]-α 1 -tert-butyl-iV 1 -(4-fluorophenyl)-3- [3-(4-fluorophenyl)propyl]--V 3 -hydroxy-2-oxo- 1 , 3-pyrroUdinediacetamide. EXAMPLE 147 Preparation of [S-(i?*-R*)]-α 1 -fert-butyl-3-[3-(4- fluorophenyl)propyl]-iv^-hydroxy-2-oxo-iV 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 148 Preparation of [S-(i?*J^*))-α 1 -cyclohexyl-3-[3-(4- fluorophenyl)propyl]-N 3 -hydroxy-N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 149 Preparation of [S-(β*J2*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-3-[3-(4- fluorophenyl)propyl]-N 3 -hydroxy-2-oxo- 1 ,3-pyrroUdinediacetamide. EXAMPLE 150 Preparation of [S-CR*JΪ*)]-α 1 -cyclohexyl-3-[3-(4- fluorophenyl)propyl]-N -hydroxy-2-oxo-N -phenyl- 1,3-pyrrohdinediacetamide. EXAMPLE 151 Preparation of [S-(Λ*JΪ*)]-α 1 -cyclohexyl-N 1 -(4-fluorophenyl)-3- [S^-fluorophenyDpropyU-Λ^-hydroxy^-oxo-l.S-pyrroUdinediacetamide. EXAMPLE 152 Preparation of [S-(i?*-R*)]-α 1 -cyclohexyl-3-[3-(4- fluorophenyl)propyl]-N -hydroxy-2-oxo-iV ' -(4-pyridinyl)-l,3-pyrτoUdinediacetamide. EXAMPLE 153 Preparation of [S-(iJ*J2*)]-3-[3-(biphen-4-yl)propyl]-iV 3 -hydroxy- N^methyl-α 1 ^ l-methylethyl)-2-oxo- 1,3-pyrroUdinediacetamide. EXAMPLE 154 Preparation of [S-(i?*-R*)]-3-[3-(biphen-4-yl)propyl]-N 1 - cyclopropyl--V 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 155 Preparation of [S-(β*J2*)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy- α 1 -(l-methylethyl)-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 156 Preparation of [S-(i?*-R*)]-3-[3-(biphen-4-yl)propyl]-N 1 -(4- fluorophenyl)-Λ^-hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 157 Preparation of [S-(Λ*J *)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy- α 1 -( l-methylethyl)-2-oxo-N 1 -(4-pyridinyl)- 1,3-pyrroUdinediacetamide. EXAMPLE 158 Preparation of [S-(R* ,fl* )]-3-[3-(biphen-4-yl)propyl]-α l -tert- butyl-iv^-hydroxy-^-methyl^-oxo-l.S-pyrroUdinediacetamide. EXAMPLE 159 Preparation of [S-(β*J?*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert- butyl-iV 1 -cyclopropyl-iV 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 160 Preparation of [S-(i2*J2*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert- butyl-N 3 -hydroxy-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 161 Preparation of [S-(iϊ*JΪ*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert- butyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-2-oxo- 1,3-pyrroUdinediacetamide. EXAMPLE 162 Preparation of [S-( ?*JJ*)]-3-[3-(biphen-4-yl)propyI]-a 1 -tert- buryl-iV 3 -hydroxy-2-oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 163 Preparation of [S-(R* J?*)]-3-[3-(biphen-4-yl)propyl]-α 1 - cyclohexyl-Λ^-hydroxy-N -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 164 Preparation of [-?-(β*J^*)]-3-[3-(biphen-4-yl)propyl]-α 1 - cyclohexyl-N -cyclopropyl-N -hydroxy^-oxo- 1 ,3-pyrroUdinediacetamide. EXAMPLE 165 Preparation of [S-(R* J2*)]-3-[3-(biphen-4-yl)propyl]-a 1 - cyclohexyl-iV^-hydroxy-2-oxo-N -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 166 Preparation of [S-(2?*J2*)]-3-[3-(biphen-4-yl)propyl]-α 1 - cyclohexyl- 1 -(4-fluorophenyl)-iV^-hydroxy-2-oxo-l,3-pyrroUd ediacetamide. EXAMPLE 167 Preparation of [S-(Λ*-β*)]-3-[3-(biphen-4-yl)propyl]-α 1 - cy ohexyl-iV 3 -hydroxy-2-oxo-N 1 -(4-pyridmyl)-l,3-pyrroUdmediacetamide. EXAMPLE 168 Preparation of [S-(Λ*Jϊ*)]-3-t3-(4 , -fluorobiphen-4-yl)propyl]-N 3 - hydroxy-N 1 -methyl-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 169 Preparation of [S-(Λ*J?*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 - cyclopropyl-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 170 Preparation of [S-(Λ*-R*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 - hydroxy-α x -( l-methylethyl)-2-oxo-N 1 -phenyl- 1 ,3-pyrroUdinediacetamide . EXAMPLE 171 Preparation of [S-(i?*J2*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 - (4-fluorophenyl)-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 172 Preparation of [S-(ie*-R*)]-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-iV 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 173 Preparation of tS-(i?*J2*)]-α 1 -tert-butyl-3-t3-(4 , -fluorobiphen-4- yl)propyl]-N 3 -hydroxy-iV 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 174 Preparation of [S-(i2*-R*)]-a 1 -tert-butyl-N 1 -cyclopropyl-3-[3-(4' fluorobiphen-4-yl)propyl]-7^-hydroxy-2-oxo-l,3-pyrroUd ediacetamide. EXAMPLE 175 Preparation of [S-(i?*-R*)]-α 1 -tert-butyl-3-[3-(4'-fluorobiphen-4- yDpropyll-iv^-hydroxy^-oxo-^-phenyl-l.S-pyrroUdinediacetamide. EXAMPLE 176 Preparation of [S-(i2*J?*)]-α 1 -tert-butyl-3-[3-(4 , -fluorobiphen-4- yl)propyl]-N 1 -(4-fluorophenyl)-Λr-hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 177 Preparation of [S-( β * r R*)]-α 1 -tβrt-butyl-3-[3-(4'-fluorobiphen-4- yl)propyl]-_\T-hydroxy-2-oxo-N -(4-pyridinyl)-l,3-pyrroUdinediacetamide. EXAMPLE 178 Preparation of [S-(i?*Jϊ*)]-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4- yl)propyl]-N 3 -hydroxy-N 1 -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 179 Preparation of [S-(β*-β*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-3-[3-(4'- fluorobiphen-4-yl)propyl]-N 3 -hydroxy-2-oxo- 1,3-pyrroUdinediacetamide. EXAMPLE 180 Preparation of [S-(Λ*J?*)]-α 1 -cyclohexyl-3-[3-(4'-fluorobiphen-4- yl)propyl]-N 3 -hydroxy-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 181 Preparation of [S-(i?*- β *)]-α 1 -cyclohexyl-3-[3-(4'-fluorobiphen-4- yl)propyl]-N 1 -(4-fluorophenyl)-N 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 182 Preparation of [S-(Λ*J2*)]-α 1 -cyclohexyl-3-t3-(4 , -fluorobiphen-4- yl)propylj-Λ -hydroxy-2-oxo-.-V -(4-pyridinyl)- 1,3-pyrroUdinediacetamide. EXAMPLE 183 Preparation of [S-(ie*J2*)]-3-heptyl-N 3 -hydroxy-N 1 -methyl-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 184 Preparation of [S-(i?*J?*)]-N 1 -cyclopropyl-3-heptyl-iV 3 -hydroxy- α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 185 Preparation of [S-(iϊ*-R*)]-3-heptyl-iV 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-N 1 -phenyl-l,3-ρyrroUdinediacetamide. EXAMPLE 186 Preparation of tS-(i2*J?*)]-3-heptyl-N 1 -(4-fluorophenyl)-N θ - hydroxy-α -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 187 Preparation of [S-(i2*J2*)]-3-heptyl-N 3 -hydroxy-a 1 -(l- methylethyl)-2-oxo-iV -(4-pyridinyl)- 1,3-pyrroUdinediacetamide. EXAMPLE 188 Preparation of [S-(R* Jl*)]- 1 -tert-butyl-3-heptyl-N 3 -hydroxy- N -methyl-2-oxo-l,3-pyrroUd ediacetamide. EXAMPLE 189 Preparation of [S-(i2*J2*)]-α 1 -tert-butyl-iV 1 -cyclopropyl-3-heptyl- N -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 190 Preparation of [S-( β *J2*)]-α 1 -tert-butyl-3-heptyl-N 3 -hydroxy-2- oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 191 Preparation of [S-(β* f R*)]-α 1 -tert-buryl-N 1 -(4-fluorophenyl)-3- heptyl-N 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 192 Preparation of [S-(R*Jt* )]-α ^tert-butyl-S-heptyl-Λ^-hydroxy^- oxo-N -(4-pyridinyD- 1,3-pyrroUdinediacetamide. EXAMPLE 193 Preparation of [S-(ie*-R*)]-α 1 -cyclohexyl-3-heptyl-iV 3 -hydroxy- N -methyl-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 194 Preparation of [S-( β * r R*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-3- heptyl-i^-hydroxy^-oxo-l.S-pyrroUdinediacetamide. EXAMPLE 195 Preparation of [S-(Λ*J2*)]-α 1 -cyclohexyl-3-heptyl-iV 3 -hydroxy-2- oxo-N -phenyl-l,3-pyrroUdinediacetamide. EXAMPLE 196 Preparation of [S-(β*J?*)]-α 1 -cyclohexyl-3-heptyl-N 1 -(4- fluorophenyl)-N 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide. EXAMPLE 197 Preparation of [S-(R*JΪ* )]-α 1 -cyclohexyl-3-heptyl-N 3 -hydroxy-2- oxo-N -(4-pyridinyl)- 1,3-pyrroUdinediacetamide. SCHEME A-l 15 25 35 SCHEME A-2 16 35 SCHEME A-3 19 21 20 22 SCHEME A-4 24 28 25 29 20 1 26 30 27 31 35 SCHEME A-5 34 35 36 38 41 SCHEME B 10 42 20 43 30 35 SCHEME C-l 44 R 45 15 46 20 47 48 35 SCHEME C-2 49 50 15 51 25 52 35 SCHEMED 0 ^y» 53 10 54 55 56 57 58 35

Claims: CLAIMS We claim; 1. A compound of formula I R is d) -(CH 2 ) j -Aryl - Aryl, e) -(CH^j -Aryl -(CH 2 )j -Aryl, f) (CH 2 )j -Het, or g) -(CH 2 ) j -cycloalkyl Rg and R 7 may be the same or differently a) H, b) '1-6 alkyl, 0 -(CH 2 )j -Aryl, d) Q, or e) Rg and R 7 taken together with the linking N-atom form azetidinyl, pyrroUdinyl, piperazinyl, piperidinyl, or morphoUnyl, optionaUy substituted with one or more C^ alkyl; Re is a) -S-R 5 , b) -SO-R '5> c) -SO 2 -R 5 , d) -S-CCH^j -Het, e) -NHC0 2 R 5 , f) piperidinyl, x Aryl is phenyl, optionaUy substituted with one or more of the foUowing: a) halogen, b) C 1 0 alkyl, c) -OR 5 , d) -NR 5 R 5 , e) -CONHR 5 , f) -S0 2 NHR 5 , g) -NHS0 2 R 5 , h) -N0 2 , i) -C0 2 R 5 , or j) -CF 3 ; Het is a 5-, or 6-membered heteroaromatic moiety having one or more atoms selected from the group consisting of N, O, and S; Q is a saturated 5, or 6-membered heterocycUc moiety having 1-2 atoms selected from the group consisting of N, O, and S; i is 1, 2, 3, 4, 5 or 6; j is 0, 1, 2, 3, or 4; k is 2, 3, or 4; n is 0, 1, 2, 3, or 4; Ci 6 alkyl, C, , Q alkyl, or C j _ 2 g alkyl in each of the above definitions, may be each and independently substituted with one to three halogen, hydroxy, or cyano; and with the proviso that when R j is methylbutyl R 4 is other than H. 2. A compound of formula I according to claim 1 which is an opticaUy pure enantiomer having structure II. II 3. A compound of formula I according to claim 1 which is an opticaUy pure enantiomer having structure III. IH 4 A compound of formula I according to claim 1 which is an opticaUy pure enantiomer having structure IV. IV 5. A compound of formula I according to claim 1 which is an opticaUy pure enantiomer having structure V. 6. A compound of formula I according to claim 1 which is an optically pure enantiomer having structure VI. VI 7. A compound of formula I according to claim 1 which is an opticaUy pure enantiomer having structure VII. vπ 8. A compound of claim 1 wherein R j is 2-methylpropyl, or 3-methylbutyl. 9. A compound of claim 1 wherein R 2 is selected from the group consisting of H, methyl, 2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2-yDethyl, 2-(l,3-dihydro-l,3-dioxo-2H- naphthoisoindol-2-yl)ethyl, 2-(4,5,6,7,-tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2- yDethyl, 2-(5.6,-dichloro- l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(5-amino-l,3- dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(4-nitro-l,3-dihydro-l,3-dioxo-2H-isoindol- 2-yl)ethyl, 2-(5-nitro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(4-fluoro-l,3- dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(4,7-difluoro-l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl, 2-(5-fiuoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl, 2-(l,3- dihydro-l,3-dioxo-2H-isoindol-2-yl)propyl, 2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)methyl, 2-(2-thienylthio)propyl, and 2-(2-thienylthio)methyl. 10. A compound of claim 1 wherein Rg is selected from the group consisting of H, 2-methylpropyl, cyclohexylmethyl, benzyl, and phenyl. 11. A compound of claim 1 wherein R 4 is H or acetamide. 12. A compound of claim 1 wherein said compound of formula I is la) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3- pyrroUdineacetamide, lb) (3S)-N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide, lc) N-Hydroxy-α-methyl-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdineacetamide, Id) α-t2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, le) (3S)-α-[2-( l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, If) α-[2-(l,3-Dihydro-l,3-dioxo-2H-naphthoisoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lg) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(4,5,6,7- tetrafluoro-l,3-d' ydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, lh) α-[2-(5,6-Dichloro- 1,3-dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, li) α-[2-(5-Amino-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lj) N-Hydroxy-3-(2-methylpropyl)-α-[2-(4-nitro- 1 ,3-dihydro- l,3-dioxo-2H- isoindol-2-yl)ethyl]-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, Ik) N-Hydroxy-3-(2-methylpropyl)-α-t2-(5-nitro-l,3-dihydro-l,3-dioxo-2H- isoindol-2-yl)ethyl]-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 11) α-[2-(4-Fluoro-l,3-dilιydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lm) α-[2-(4,7-Difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, In) α-[2-(5-Fluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy- 3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lo) α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)propyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lp) α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)methyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lq) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(2- thienylthio)ethyl]-3-pyrroUdineacetamide, lr) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-o [2-(2- trύenylthio)propyl]-3-pyrroUdineacetamide , Is) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(2- tmenylthio)methyl]-3-pyrroUdineacetamide, It) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-l,3- pyrroUdinediacetamide, lu) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- 1,3-pyrroUdinediacetamide, lv) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(phenylmethyl)-3- pyrroUdineacetamide, lw) α-[2-( 1,3-Dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo- l-(phenylmethyl)-3-pyrroUdineacetamide , lx) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(phenylmethyl)-α-[2-(4,5,6,7- tetrafluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, ly) l-(3-Fluorophenyl)methyl)-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N-hydroxy-3-(2-methylpropyi)-2-oxo-3-pyrroUdineacetamide, lz) α 3 -[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N 3 -hydroxy-N 1 - methyl-3-(2-methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 2a) N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 3 -[2-(4,5,6,7- tetrafluoro- 1,3-dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl]- 1,3-pyrroUdinediacetamide, 2b) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenyhnethyl)-l,3-pyrroUdinediacetamide, 2c) [S,R-(R*, R*)]-α 3" [2-(l,3-Duιydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N 3 - hy droxy-N 1 -methyl-3-(2-methylpropyl)-2 -oxo-α 1 -(phenylmethyl)- 1,3- pyrroUdinediacetamide, 2d) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2e) [S-(R*, R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -(2-phenethyl)-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2f) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-α 1 ,3-bis (2-methylpropyl)-2-oxo- 1,3-pyrroUdinediacetamide, 2g) [S-(R*, R*)]-α 1 -(Cyclohexylmethyl)-N 3 -hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 2h) [S-(R*, R*)]-N 3 -Hydroxy-N 1 -methyl-3-(3-methylbutyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 2i) N-Hydroxy-3-(2-methylpropyl)-2,5-dioxo- l-(2-phenylethyl)-3- pyrroUdineacetamide, 2j) N-HydiOxy-3-methyl-4-(2-methylpropyl)-2,5-dioxo-l-(2-phenylethyl)-4- imidazoUdineacetamide, 2k) N-Hydroxy-4-(2-methylpropyl)-2,5-dioxo- l-(2-phenylethyl)-4- imidazoUdineacetamide, 21) N-Hydroxyl-4-(2-methylpropyl)-5-oxo-l-(2-phenylethyl)-4- pyrazoUdineacetamide monohydrochloride, 2m) [S-(β* Je*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -phenyl-α 1 - (phenylmethyl)- 1 ,3-pyrroUdinediacetamide , 2n) [S-(Λ* r β*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(2-pyridinylmethyl)-l,3-pyrroUdinediacetamide, 2o) [S-(ie*-β*)]--V 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyD- N -<4-pyridinyl)-l,3-pyrroUdinediacetamide, 2p) [S-(R* J?* )]-N 1 -(4-Fluorophenyl)-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo- α -(phenylmethyl)- 1 ,3-pyrroUdinediacetamide, 2q) [S-(Λ*J?*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -[l-(phenylmethyl)-4-piperdinyl]-l,3-pyrroUdinediacetamide, 2r) [S-(R* J?* )]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(4-piperdinyl)-l,3-pyrroUdinediacetamide, 2s) /S-( β *-R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(4-pyridinylmethyl)-l,3-pyrroUdinediacetamide, 2t) [S-(Λ* r β *)]-N 1 -(4-Fluorophenylmethyl)-N 3 -hydroxy-3-(2-methylpropyl)- 2-oxo-α -(phenylmethyl)-l,3-pyrroUdinediacetamide, 2u) [S-(R* JR* )]-N '3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(2- phenylethyl)-l,3-pyrroUdinediacetamide, 2v) [S-(Λ*J?*)]-N 3 -Hydroxy-3-(2-methylpropyl ) -2-oxo-α 1 -(2-phenylethyD- N -(phenylmethyl)-l,3-pyrroUdinediacetamide, 2w) [S-(R* J?* )]-N 3 -Hydroxy-α 1 ,3-bis(2-methylpropyl)-2-oxo-iV 1 -2-p yridinyl- 1,3-pyrroUdinediacetamide, 2x) [S-(/2*J?*)]-a 1 -Cyclohexyl-iV 3 -hydroxy-iV 1 -methyl-3- ( 2-methylpropyl)-2- oxo- 1,3-pyrroUdinediacetamide, 2y) [S-(i2* R*)]-a 1 -Cyclohexyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-iV 1 -2- pyridinyl- 1,3-pyrroUdinediacetamide, 2z) [S-(Λ* r R*)]-3-(Cyclopentylmethyl)-N 3 -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, 3a) [S-(i2* β *)]-3-(Cyclopentylmethyl)-N 3 -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)- 1,3-pyrroUdinediacetamide, 3b) [3S-tl(Λ*),3i2*( β *)]]-α 3 -[2-(Benzoylamino)ethyl]-N 3 -hy(lroxy-N 1 - methyl-3-(2-methylpropyl)-2-oxo-α -(phenylmethyl)-l,3-pyrroUdinediacetamide, 3c) [S-(R* -R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-iV 1 -[2-(4- morphoUnyl)ethyl]-2-oxo-α -(phenylmethyl)-l,3-pyrroUdinediacetamide, 3d) [S-(Λ*J?*)]-N-Hydroxy-3-(2-methylpropyl)-l-[2-(4-morphoUnyl)-2-oxo-l- (phenylmethyl)ethyl]-2-oxo-3-pyrroUdineacetamide, 3e) [l(lS)-[l[β*(β*)], 3α,5α]]-l-[2-(3,5-Dimethyl-l-piperazinyl)-2-oxo-l- (phenylmethyl)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 3f) [S-(JR*J?*)]-iV 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -2-pyridinyl- 1 ,3-pyrroUdinediacetamide, 3g) [3S-[l(i?*),3β*(i2*)]]-α 3 -t2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2- yl)ethyl]-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(pheny ιethyl)-l,3- pyrroUdinediacetamide, 3h) [S-(β* R*)]-α 1 -Cyclohexyl-N 1 -cyclopropylmethyl-iV 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 3i) [S-(β*J^*)]-α 1 -Cyclohexyl-N 1 -(4-fiuorophenyl)-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 3j) [S-(β* r R*)]-α 1 -tert-Butyl--V 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2- oxo- 1,3-pyrroUdinediacetamide, 3k) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-t2-(5- propyloxy-l,3-o hydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, 31) [R-(R*,S*)]-5-Fluoro-l > 3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrroUdinyl]- l,3-dioxo-2i-r-isoindole-2-butanamide, 3m) a-[2-(5,6-Difluoro-l,3-dU ydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3n) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2-(5- trifiuoromethyl-l,3-d^ydro-l,3-dioxo-2H-isoindol-2-yl)etiιyl]-3-pyrroUdineacetamide, 3o) α-[2-(l,3,4,5,6,7-Hexahydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-iV- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3p) α-[2-( 1,3-Dihydro- l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(3-phenylpropyl)-3-pyrroUdineacetamide, 3q) l-[2-(4-Fluorophenyl)ethyl]-α-[2-( 1,3-dihydro- l,3-dioxo-2H-isoindol-2- yl)ethyl]-iV-hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 3r) α-[2-(o-benzoic sulfimide)ethyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo- 1- (2-phenylethyl)-3-pyrroUdineacetamide, 3s) Ethyl Phenylmethyl [4-(hydroxyamino)-3-[3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdinyl]-4-oxobutyl]imidodicarbonate, 3t) S-(β*J?*)]-l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdinyl]-l,3-dioxo-2H-isoindole-2-butanamide, 3u) l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-[2-(4- fluorophenyl)ethyl]-3-pyrrolidinyl]-l,3-dioxo-2H-isoindole-2-butanamide, 3v) α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)- 2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, 3w) [i2-(β*,S*)-α-[2-t(3-Fluorobenzoyl)amino]ethyl]-iV-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3x) a-[2-[(4-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3y) N-Hydroxy-3-(2-methylpropyl)-α-[2-[(3-nitrobenzoyl)amino]ethyl]-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, 3z) α-[2-[(3-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4a) α-[2-[(3-Fluorobenzoyl)amino]ethyl]-l-[2-(4-fluorophenyl)ethyl]-iV ' - hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 4b) α-[2-[(4-Biphenylcarbonyl)amino]ethyl]-N-hydroxy-3-(2-methylpropyl)- 2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, 4c) N-Hydroxy-α-[2-[[(4-methylphenyl)suUOnyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4d) α-[2-t[(4-Fluorophenyl)suUOnyl]amino]ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4e) N-Hydroxy-α-[2-[[(4-methoxyphenyl)sulfonyl]amino]ethyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4f) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2- [(phenylsulfonyl)amino]ethyl]-3-pyrroUάιneacetamide, 4g) [R-(R*,S* )]-α-[2-[[(4-Fluorophenyl)suUonyl]amino]ethyl]-iV-hydroxy-3- (2-methylpropyl)-2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide , 4h) 5,6-Difluoro-l,3-dihydro-iV-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 4i ) l,3-Dilιydro-iV-hydroxy-α-t3- ( 2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 4j) [ β -(B*,S*)]-6-Fluoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2- oxc^l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2i_ -isoindole-2-butanamide, 4k) [Λ-(Λ*,5*)]-5-Fluoro-l,3-dihydro-jV-hydroxy-α-[3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrroUdinyl]- l-oxo-2fl r -isoindole-2-butanamide, 41 ) [22-(f?*HS*)]-5,6-Difluoro-l,3-dihydro-N-hydroxy-a-[3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrroUdinyl]- l-oxo-2H-isoindole-2-butanamide, 4m) N-Hydroxy-α-[[[(4-methoxyphenyl)suUOnyl]amino]-methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αR-diastereomer), 4n) N-Hydroxy-α-[[[(4-methoxyphenyl)suUOnyl]amino]-methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αS-diastereomer), o) α-[[(4-Fluorophenyl)sulfonyl]amino]-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (R-diastereomer), 4p) α-[[(4-Fluorophenyl)sulfonyl]amino]-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrπ>Udineacetamide (αS-diastereomer), 4q) α-[2-[(3,4-Difluorobenzoyl)amino]ethyl3-N-hydroxy-3-(3-hydroxypropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4r) α-[2-[(3,4-Difluorobenzoyl)amino]ethyl]-N-hydroxy-3-(2-hydroxyethyl)- 2-oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, 4s) [R-(R*,S*)]-α-[2-[(3-Fluorobenzoyl)amino]ethyl]-N-hydroxy-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 4t) S-(Λ* r R*)]--V 3 -hydroxy-iV *1 -methyl-α 1 -( l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 4u) [S-(i?*Ji*)]-N 1 -cyclopropyl--V 3 -hydroxy-a 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide., 4v) [S-(β*.R*)]--V 3 -hydroxy-α 1 -(l-methylethyl)-3-(2-methylpropyl)-2-oxo- iV -phenyl- 1,3-pyrroUdinediacetamide, 4w) [S-(β*J2*)]-N 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 -(l-methylethyl)-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 4x) [S-(.R*-R*)]-N 3 -hydroxy-α 1 -(l-methylethyl)-3-(2-methylpropyl)-2-oxo- N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 4y) [S-(iJ*J?*)]-α 1 -tert-butyl-N 1 -cyclopropyl-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 4z) [S-(-e* β*)]-α 1 -tert-butyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-N 1 - phenyl- 1,3-pyrroUdinediacetamide , 5a) [S-(β*-R*)]-α 1 -teri-butyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 5b ) [S-(-R*J2*)]-α 1 -tert-butyl-N 3 -hydroxy-3- ( 2-methylpropyl)-2-oxo-N 1 -(4- pyridinyl)-l,3-pyrroUdinediacetamide, 5c ) [S-(i?* r R*)]-α 1 -cyclohexyl-N 3 -hydroxy-3-(2-methylpropyl)-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 5d) [S-(i?* r R*)3-α 1 -cyclohexyl-N 3 -hydroxy-3- ( 2-methylpropyl)-2-oxo-N 1 -(4- pyridinyl)- 1 ,3-pyτroUdinediacetamide, 5e) [S , -(i?*J?*)]-3-(cyclopentyunethyl)-N 3 -hydroxy--V 1 -methyl-α :l -( 1- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 5f) [S-(ie* R*)]-3-(cyclopentylmethyl)-iV 1 -cyclopropyl-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 5g) [S-( β *J?*)]-3-(cyclopentylmethyl)-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo- N 1 -phenyl-l ) 3-pyrroUdinediacetamide, 5h) [S-(Λ*-ff*)]-3-(<yclopentylmethyl)-iV 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 5i ) [S-( β *J2*)]-3-(cyclopentylmethyl)-N 3 -hydroxy- 1 -(l-methylethyl)-2-oxo- N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 5j) [S-(iJ*-R*)]-a 1 -fert-butyl-3- ( cyclopentylmethyl)-iV 3 -hydroxy-N 1 -methyl- 2-oxo-l,3-pyrroUdinediacetamide, 5k) [S-(Λ* R*)]-α 1 -tert-butyl-3-(cyclopentylmethyl)-iV 1 -cyclopropyl-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 51) [S-(i?*-R*)]-α 1 -tert-butyl-3- ( cyclopentylmethyl)-N 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 5m ) [S-(B* R*)]-α 1 -terr-butyl-3-(cyclopentylmethyl)-iV 1 -(4-fluorophenyl)-iV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5n) tS-(Λ*-R*)]-α 1 -fert-butyl-3- ( cyclopentyhnethyl)-iV 3 -hydroxy-2-oxo-iV 1 -(4- pyridinyl)-l,3-pyrroUdinediacetamide, 5o ) [5-(Λ* R*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-iV 3 -hydroxy-N 1 -methyl- 2-oxo-l,3-pyrroUdinediacetamide, 5p) [S-(-R* r R*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl ) -N 1 -cyclopropyl- V 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5q) [S-(i2* r β *)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-N 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 5r) [S-(i?* r R*)]-α 1 -cyclohexyl-3-(cyclopentylmethyl)-N 1 -(4-fluorophenyl)-N 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 5s) [S-(i2*J2*)]-a 1 -cyclohexyl-3-(cyclopentylmethyl)-iV 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)- 1,3-pyrroUdinediacetamide, 5t) [S-(i2*J2*)]-iV 3 -hydroxy-N 1 -methyl-a 1 -(l-methylethyl)-2-oxo-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetamide, 5u) [S-(Λ*JΪ*)]-iV 1 -cyclopropyl-N 3 -hydroxy-α 1 -( l-methylethyl)-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 5v) [S-(i2* r ff*)]--V 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-N 1 -phenyl-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetami de, 5w) tS-(Λ*-R*)]-N 1 -(4-fluorophenyl)-iV 3 -hydroxy-α 1 -( l-methylethyl)-2-oxo-3- (3-phenylpropyl)-l,3-pyrroUdinediacetamide, 5x) [S-(iϊ*-R*)]-N 3 -hydroxy-α 1 -(l-methylethyl)-2-oxo-3-(3-phenylpropyl)- N -(4-pyridinyl)- 1 ,3-pyrroUdinediacetamide, 5y) tS-(β* r R*)]-α 1 -tert-butyl-N 3 -hydroxy-Λr 1 -methyl-2-oxo-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetamide, 5z) tS-(β*Jf*)]-α 1 -tert-butyl-N 1 -cyclopropyl-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6a) [S-(β* R*)]-α 1 -fert-butyl-N 3 -hydroxy-2-oxo-N '1 -phenyl-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6b) [S-(R* τ R*)]-α 1 -tert-butyl-N 1 -(4-fiuorophenyl)-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6c) tS-(i?* r R*)3-α 1 -tert-butyl-N 3 -hydroxy-2-oxo-3-(3-phenylpropyl)-N 1 -(4- pyridinyl)-l,3-pyrroUdinediacetamid, 6d) [S-(β* r R*)]-α 1 -cyclohexyl--V 3 -hydroxy-N 1 -methyl-2-oxo-3-(3- phenylpropyl)- 1,3-pyrroUdinediacetamide, 6e) [S-(Λ*J2*)]-α 1 -cyclohexyl-iV 1 -cyclopropyl-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6f) [S-(i?* K*)]-a 1 -cyclohexyl-N 3 -hydroxy-2-oxo-iV 1 -phenyl-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6g) [S-(β* R*)]-α 1 -cyclohexyl-N '1 -<4-fiuorophenyl)-N 3 -hydroxy-2-oxo-3-(3- phenylpropyl)-l,3-pyrroUdinediacetamide, 6h) [S-(i?*,fl*)]-α 1 -cyclohexyl-iV 3 -hydroxy-2-oxo-3-(3-phenylpropyl)-N :l -(4- pyridinyl)-l,3-pyrroUdinediacetamide, 6i) [S-(i2* > R*)]-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-N 1 -methyl-α 1 -(l- methylethyl)-2-oxo-l,3-pyrrolidinediacetamide, 6j) [S-(i?* r β *)3-N 1 -cyclopropyl-3-[3-(4-fluorophenyl)propyl]-iV 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6k) [S-(B* r R*)3-3-[3-(4-fluorophenyl)propyl3-N 3 -hydroxy-α 1 -(l-methylethyl)- 2-oxo-N -phenyl- 1,3-pyrroUdinediacetamide, 61) [S-(B* r R*)3-N 1 -(4-fiuorophenyl)-3-[3-(4-fluorophenyl)propyl]-N 3 - hydroxy-α -( l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6m) [S-(iϊ* r R*)]-3-[3-(4-fiuorophenyl)propyl3-iV 3 -hydroxy-α :l -(l-methylethyl)- 2-oxo-N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 6n) [S-( β * r R*)3-α 1 -tert-butyl-3-[3-(4-fluorophenyl)propyl]-N 3 -hydroxy-N 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 6o) [S- R* R*)3-α 1 -tert-butyl-N 1 -cyclopropyl-3-[3-(4-fiuorophenyl)propyl]- Λr-hydroxy~2-oxo-l,3-pyrroUdinediacetamide, 6p) [S-(JS*Je*)3-α 1 -t-err-butyl-3-[3-(4-fluorophenyl)propyl3--V 3 -hydroxy-2-oxo- N -phenyl- 1,3-pyrroUdinediacetamide, 6q) [S-(i2* r ff*)]-α 1 -fert-butyl-iV 1 -(4-fluorophenyl)-3-[3-(4-fiuorophenyl)- propyl3-N^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 6r) [S-(Λ* r R*)3-α 1 -tert-butyl-3-[3-(4-fluorophenyl)propyl]-iV 3 -hydroxy-2-oxo- N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 6s) [S-CR* β* )3-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyl3-N 3 -hydroxy-N 1 - methyl-2-oxo- 1,3-pyrroUdinediacetamide, 6t) [S-(R*Jt* )3-α 1 -cyclohexyl-N 1 -cyclopropyl-3-[3-(4-fluorophenyl)propyl3- Λ^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 6u) [S-(i2*J?*)]-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyI3-N 3 -hydroxy-2- oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide, 6v) [S-(β*J?*)3-α 1 -cyclohexyl-_V 1 -(4-fluorophenyl)-3-[3-(4- fluorophenyl)propyl]--\ -hydroxy-2-oxo- 1 ,3-pyrroUdinediacetamide , 6w) [S-(JΪ*J?*)]-α 1 -cyclohexyl-3-[3-(4-fluorophenyl)propyl3-N 3 -hydroxy-2- oxo-N -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 6x ) [S-(i2* R*)3-3-[3-(biphen-4-yl)propyl3-N 3 -hydroxy-N 1 -methyl-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6y) [S-( β * r β *)3-3-[3-(biphen-4-yl)propyl3-N 1 -cyclopropyl-iV 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 6z) tS-(R* R*)]-3-[3-(biphen-4-yl)propyl3-N 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-N -phenyl- 1,3-pyrroUd ediacetamide, 7a) [S-(i2*-R*)]-3-[3-(biphen-4-yl)propyl]-iV 1 - ( 4-fluorophenyl)-N 3 -hydroxy- α -( l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 7b) [S-(R*J2*)]-3-[3-(biphen-4-yl)propyl]-N 3 -hydroxy-α 1 -( l-methylethyl)-2- oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 7c) [S-(β* r R*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-iV 3 -hydroxy-iV 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 7d) [S-(R*^*)]-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-N 1 -cyclopropyl-JV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7e) [S-(i2* R*)3-3-[3-(biphen-4-yl)propyl3-α 1 -tert-butyl-iV 3 -hydroxy-2-oxo-iV 1 - phenyl- 1,3-pyrroUdinediacetamide, 7f) [S-(R*J?*)3-3-[3-(biphen-4-yl)propyl]-α 1 -fert-butyl-N 1 -(4-fluorophenyl)- iV -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7g) [S-(R*J^*)3-3-[3-(biphen-4-yl)propyl]-α 1 -tert-butyl-iV 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)- 1,3-p yrroUdinediacetamide, 7h) [S-(ie* r R*)]-3-[3-(biphen-4-yl)propyl3-α 1 -cyclohexyl-N 3 -hydroxy-iV 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 7i) [S-(β*Ji*)3-3-[3-(biphen-4-yl)propyl3-α 1 -cyclohexyl-N 1 -cyclopropyl-JV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7j) [S-(R*-R*)]-3-[3-(biphen-4-yl)propyl3-α 1 -cyclohexyl-iV 3 -hydroxy-2-oxo- -V -phenyl-l,3-pyrroUdmediacetamide, 7k) [S-(R* r R*)]-3-[3-(biphen-4-yl)propyl3-α 1 -cyclohexyl-N 1 -(4-fluorophenyl)- Λ^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 71) [5-(Λ* r R*)]-3-[3-(biphen-4-yl)propyl3-α 1 -cyclohexyl-N 3 -hydroxy-2-oxo- iV 1 -(4-pyridinyl)-l,3-pyrroUdinediacet^-mide, 7m) [S-(i?;* R*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-iV 3 -hydroxy-iV 1 -methyl-α 1 - ( l-methylethyl)-2-oxo- 1,3-pyrroUdinediacetan ide, 7n) [S-(R* J?*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 -cyclopropyl-N 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-l > 3-pyrroUdinediacetamide, 7o) [S-(R* R*)]-3-[3-(4 , -fiuorobiphen-4-yl)propyl]-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide, 7p) [S-(R* r R*)]-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 1 -(4-fluorophenyl)-N 3 - hydroxy-α 1 -(l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 7q) [S-(R*.R*)]-3-[3-(4'-fiuorobiphen-4-yl)propyl]-iV 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-N 1 -(4-pyridinyl)-l,3-pyrroUdinediacetamide, 7r) [S-(R*-R*)]-α 1 -tert-butyl-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 3 -hydroxy- N^methyl^-oxo-l.S-pyrroUdinediacetamide, 7s) [S-(Λ* r R*)]-α 1 -tert-butyl-N 1 -cyclopropyl-3-[3-(4'-fluorobiphen-4- yl)propyl]-N 3 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7t) [5-(Λ* R*)]-α 1 -tert-butyl-3-[3-(4'-fiuorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo-N -phenyl-l,3-pyrroUdinediacetamide, 7u) [S-(R* r R*)]-α 1 -tert-butyl-3-[3-(4 , -fiuorobiphen-4-yl)propyl]-N 1 -(4- fluorophenyl)-N^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 7v) [S-( β *^2*)]-α 1 -tert-butyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo-iV -(4-pyridinyl)-l,3-pyrroUdinediacetamide ) 7w) [S-(R*- β *)3-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-iV 3 -hydroxy- N -methyl-2-oxo-l,3-pyrroUdinediacetamide, 7x) [iS-(R*J2*)]-α 1 -cyclohexyl-N 1 -cyclopropyl-3-[3-(4 , -fiuorobiphen-4- yl)propyl]-.V^-hydroxy-2-oxo- 1,3 -pyrroUdinediacetamide, 7y) t5-(R* r R*)]-α 1 -cyclohexyl-3-[3- ( 4 , -fluorobiphen-4-yl)propyl]-N 3 -hydroxy- 2-oxo-N -phenyl-l,3-pyrroUdinediacetamide, 7z) [S-(R*-R*)]-α 1 -cyclohexyl-3-[3-(4'-fluorobiphen-4-yl)propyl]-N 1 -(4- fluorophenyl)-N^-hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8a) [S-(-R*-R*)]-α 1 -cyclohexyl-3-[3-(4 , -fluorobiphen-4-yl)propyl]-iV 3 -hydroxy- 2-oxo-N -(4-pyrid yl)-l,3-pyrroUdinediacetamide, 8b) Preparation of [S-(R* R*)]-3-heptyl-N 3 -hydroxy-N 1 -methyl-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 8c) Preparation of [S-(i?* t R*)]-N 1 -cyclopropyl-3-heptyl-N 3 -hydroxy-α 1 -(l- methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 8d) Preparation of [S-(.R*- β *)]-3-heptyl-iV 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-N 1 -phenyl-l,3-pyrroUdinediacetamide, 8e ) Preparation of [5-(-S* r R*)]-3-heptyl-N 1 -(4-fluorophenyl)-N 3 -hydroxy-α 1 - (l-methylethyl)-2-oxo-l,3-pyrroUdinediacetamide, 8f ) Preparation of [_?-(Λ*J2*)]-3-heptyl-N 3 -hydroxy-α 1 -(l-methylethyl)-2- oxo-JV '1 -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, 8g ) Preparation of [S-(i2*J?*)]-α 1 -tert-butyl-3-heptyl-N 3 -hydroxy-JV 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 8h ) Preparation of [S-(.R* r R*)]-α 1 -tert-butyl-N 1 -cyclopropyl-3-hepryl-N 3 - hydroxy-2-oxo- 1,3-pyrroUdinediacetamide, 8i) Preparation of [S-(i2* R*)]-α 1 -iert-butyl-3-heptyl-N 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 8j) Preparation of [S-(R* r R*)]-α 1 -tert-butyl-N 1 - ( 4-fluorophenyl)-3-heptyl- -V 0 -hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8k) Preparation of [S-( β * R*)]-α 1 -tert-butyl-3-heptyl-iS^ 3 -hydroxy-2-oxo-N 1 - (4-pyridinyl)- 1,3-pyrroUdinediacetamide, 81) Preparation of [S-(-f2*J^*)]-α 1 -cyclohexyl-3-heptyl-N 3 -hydroxy-N 1 - methyl-2-oxo-l,3-pyrroUdinediacetamide, 8m) Preparation of [S-(-R* r R*)]-α 1 -cyclohexyl-iV 1 -cyclopropyl-3-heptyl-iV 3 - hydroxy-2-oxo-l,3-pyrroUdinediacetamide, 8n) Preparation of [S-(i2* r R*)]-α 1 -cyclohexyl-3-heptyl- 3 -hydroxy-2-oxo-N 1 - phenyl-l,3-pyrroUdinediacetamide, 8o) Preparation of [S-(R* R*)]-α 1 -cyclohexyl-3-heptyl-JV 1 -(4-fluorophenyl)- -V^hydroxy-2-oxo- 1 ,3-pyrroUdinediacetamide , or 8p) Preparation of [S-(R*-R*)]-α 1 -cyclohexyl-3-heptyl-Λ r3 -hydroxy-2-oxo--V 1 - (4-pyridinyl)-l,3-pyrroUdinediacetamide. 13. A compound of claim 12 which is la) (3S)-α-[2-(l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, lb) [S,S-(R*, R*)]-α 3 -[2-( l,3-Dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N 3 - hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide, lc) [S-(R*, R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -(2-phenethyl)-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, Id) [S-(R*, R*)]-α 1 -(Cyclohexylmethyl)-N 3 -hydroxy-N 1 -methyl-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, le) [S-(R*. R*)]-N 3 -Hydroxy-N 1 -methyl-3-(2-methylpropyl)-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, If) [S-(β* r R*)]-iV 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-N 1 -phenyl-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, lg) [S-(i?* R*)]-iV 3 -Hydroxy-3-(2-methylpropyl)-2-oxo- x 1 -(phenylmethyl)- N 1 -(2-pyridinylmethyl)-l,3-pyrroUdinediacetamide, lh) [S-(JR*Ji*)]--V 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyD- N -(4-pyridinyl)- 1,3-pyrroUdinediacetamide, li) [S-(R* r R*)]-N 1 -(4-Fluorophenyl)-JV 3 -hydroxy-3-(2-methylpropyl)-2-oxo- α -(phenylmethyl)-l,3-pyrroUdinediacetamide, lj) [S-(β*J2*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyD- N 1 -[l-(phenylmethyl)-4-piperdinyl]-l,3-pyrroUdinediacetamide, Ik) [S-(R*-R !,t )]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N 1 -(4-piperdinyl)-l,3-pyrroUdinediacetamide, 11) / ■ S-(R* r R*)]-N 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -(4-pyridinylmethyl)- 1,3-pyrroUdinediacetamide, lm) [S-(R* r R*)]-N 1 -(4-Fluorophenylmethyl)-N 3 -hydroxy-3-(2-methylpropyl)- 2-oxo-α 1 -(phenylmethyl)- 1 ,3-pyrroUdinediacetamide , In ) [S-(R* ff* ) ]-N 3 -Hydroxy-iV 1 -methyl-3- ( 2-methylpropyl)-2-oxo-α 1 -(2- phenylethyl)- 1,3-pyrroUdinediacetamide, lo) [S-(R*J?*)]-iS7 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(2-phenylethyl)- N phenymiethyl)-l,3-pyrroUdinediacetamide, lp) tS-(R*- β *)]-N 3 -Hydroxy-α 1 ,3-bis(2-methylpropyl)-2-oxo-N 1 -2-pyridinyl- 1,3-pyrroUdinediacetamide, lq ) [S-(-R*J?* ) ]-α 1 -Cyclohexyl-iV 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2- oxo-l,3-pyrroUdinediacetamide, lr) [S-(R* r R*)]-α 1 -Cyclohexyl-Λ^ 3 -hydroxy-3-(2-methylpropyl)-2-oxo-iV 1 -2- pyridinyl-l.S-pyrroUdinediacetamide, Is) [S-(-R*J^*)]-3-(Cy opentylmethyl)-N θ -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, It) [5-(R* τ β *)]-3-(Cyclopentylmethyl)-iV 3 -hydroxy-N 1 -methyl-2-oxo-α 1 - (phenylmethyl)-l,3-pyrroUdinediacetamide, lu) t3S-[l(R*),3R*(R*)]]-a 3 -[2-(Benzoylamino)ethyl]-N 3 -hydroxy-N 1 - methyl-3-(2-methylpropyl ) -2-oxo-α 1 -(phenymιethyl)-l,3-pyrroUdinediacetamide, lv) [S-(Λ* β*)3-N 3 -Hydroxy-3-(2-methylpropyl)-N 1 -[2-(4- morphoUnyl)ethyl]-2-oxo-α -(phenyimethyl)-l,3-pyrroUdinediacetamide, lw ) [S-(i2*-R*)]-iV-Hydroxy-3-(2-methylpropyl)-l-[2-(4-morphoUnyl)-2-oxo-l- (phenylmethyl)ethyl]-2-oxo-3-pyrroUdineacetamide, lx ) [l(lSm[R*(R*)l 3α,5α]]-l-[2-(3,5-Dimethyl-l-piperazinyl)-2-oxo-l- (phenylmethyl)ethyl]-N-hydroxy-3-(2-methylpropyl ) -2-oxo-3-pyrroUdineacetamide, ly) [S-(R*J2*)]-iV 3 -Hydroxy-3-(2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)- N -2-pyridinyl-l,3-pyrroUdinediacetamide, lz) [3S-[l(R* ) ,3R* ( Λ* ) ]]-o: 3 -[2-(l,3-DUιydro-l,3-dioxo-2H-isoindol-2- yl ) ethyl]--V 3 -hydroxy-N 1 -methyl-3- ( 2-methylpropyl)-2-oxo-α 1 -(phenylmethyl)-l,3- pyrroUdinediacetamide , 2a) [S-(R* r R* ) ]-α 1 -Cyclohexyl-N 1 -cyclopropylmethyl-iV 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 2b) [S-(.R*J2*)]-α 1 -Cyclohexyl-N 1 -(4-fluorophenyl)-iV 3 -hydroxy-3-(2- methylpropyl)-2-oxo-l,3-pyrroUdinediacetamide, 2c) [S-(R* -R*)]-α 1 -tert-Butyl-N 3 -hydroxy-N 1 -methyl-3-(2-methylpropyl)-2- oxo- 1 ,3-pyrroUdinediacetamide, 2d) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(5- propyloxy-l,3-d ydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-3-pyrroUdineacetamide, 2e) [R-(R*,S*)]-5-Fluoro-l,3-dihydro-JV-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylei^yl)-3-pyrrolidinyl]-l,3-dioxo-2H-isoindole-2-butanamide, 2f) α-[2-(5,6-Difluoro-l,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-iV- hydiOxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2g) N-Hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-α-[2-(5- trifluoromethyl-l,3-d^ydro-l,3-o oxo-2H-isoindol-2-yl)ethyl]-3-pyrroUα neacetar-iide, 2h) α-[2-(l,3,4,5,6,7-Hexahydro-l,3-dioxo-2H-isoindol-2-yl)ethyl]-N- hydroxy-3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyπOUdineacetamide, 2i) α-[2-( 1,3-Dihydro- 1 ,3-dioxo-2H-isoindol-2-yl)ethyl]-N-hydroxy-3-(2- methylpropyl)-2-oxo-l-(3-phenylpropyl)-3-pyrroUdineacetamide, 2j) l-[2-(4-Fluorophenyl)ethyl]-α-[2-(l,3-dihydro-l,3-dioxo-2H-isoindol-2- yl)e1_hyl]-N-hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 2k) α-[2-(o-benzoic su_lfiπ-ide)ethyl]--V-hydroxy-3-(2-methylpropyl)-2-oxo- 1- (2-phenylethyl)-3-pyrroUdineacetamide, 21) Ethyl Phenylmethyl [4-(hydroxyamino)-3-[3-(2-methylpropyl)-2-oxo-l- (2-phenylethyl)-3-pyrroUdinyl]-4-oxobutyl3imidodicarbonate, 2m) S-(β* τ R*)]-l,3-Dihydro--V-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdinyl3- 1 ,3-dioxo-2H-isoindole-2-butanamide , 2n) l,3-Dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-[2-(4- fluorophenyl)ethyl]-3-pyrroUdinyl]-l,3-dioxo-2H.-isoindole-2-butanaπύde, 2o) α-[2-t(3,4-Dύ uorobenzoyl)amino]ethyl]-iV ' -hydroxy-3-(2-methylpropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2p) [R-(R*,S*)-α-[2-[(3-Fluorobenzoyl)amino]ethyl]-V-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2q) α-[2-[(4-Fluorobenzoyl)a ino]ethyl]-iV-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2r) iV-Hydroxy-3-(2-methylpropyl)-α-[2-[(3-nitrobenzoyl)amino]ethyl3-2-oxo- 1 -(2-phenylethyl)-3-pyrroUdineacetamide , 2s) α-[2-[(3-Fluorobenzoyl)amino]ethyl3-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2t) α-[2-[(3-Fluorobenzoyl)amino]ethyl]-l-t2-(4-fiuorophenyI)ethyl3-N- hydroxy-3-(2-methylpropyl)-2-oxo-3-pyrroUdineacetamide, 2u) α-[2-[(4-Biphenylcarbonyl)amino3ethyl]-N-hydroxy-3-(2-methylpropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2v) N-Hydroxy-α-[2-[[(4-methylphenyl)sulfonyl3amino3ethyl3-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2w) α-[2-[[(4-Fluorophenyl)suUOnyl]arnino3ethyl3-JV-hydroxy-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2x) N-Hydroxy-α-[2-t[(4-methoxyphenyl)suUOnyl3amino]ethyl3-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 2y) N-Hydroxy-3-(2-methylpropyl)-2-oxo- l-(2-phenylethyl)-α-[2- [(phenylsu Onyl)ammo3ethyl]-3-pyrroUdmeacetamide, 2z) [R-(R*,S*)]-α-[2-[[(4-Fluorophenyl)sulfonyl3amino3ethyl]-iV-hydroxy-3- (2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3a) 5,6-Difiuoro-l,3-dihydro-N-hydroxy-α-[3-(2-methylpropyl)-2-oxo-l-(2- phenylethyl)-3-pyrroUdinyl3-l-oxo-2H-isoindole-2-butanamide, 3b ) l,3-Dihydro--V-hydroxy-α-t3-(2-methylpropyl)-2-oxo-l-(2-phenylethyl)-3- pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 3c) [Λ-(R*,S*)3-6-Fluoro-l,3-di-hydro-iV-hydroxy-α-[3-(2-methylpropyl)-2- oxo- l-(2-phenylethyl)-3-pyrroUdinyl3- l-oxo-2fiT-isoindole-2-butanamide, 3d) [Λ-(J?*,-5*)3-5-Fluoro-l,3-dihydro-JV-hydroxy-α-[3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUαUnylJ-l-oxo-2H-isoindole-2-butanamide, 3e ) [R-(JΪ*,S*)3-5,6-Difluoro-l,3-dihydro-iV-hydroxy-α-t3-(2-methylproρyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdinyl]-l-oxo-2H-isoindole-2-butanamide, 3f) N-Hydroxy-α-[[[(4-methoxyphenyl)sulfonyl3amino3-methyl]-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αR-diastereomer), 3g ) N-Hydroxy-α-[[[(4-methoxyphenyl)sulfonyl]amino]-methyl3-3-(2- methylpropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αS-diastereomer), 3h ) α-[[(4-Fluorophenyl)su Onyl]amino]-N ' -hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (R-diastereomer), 3i) α-[[(4-FluorOphenyl)suUOnyl3amino3-N-hydroxy-3-(2-methylpropyl)-2- oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide (αS-diastereomer), 3j ) α-[2-[(3 ,4-Difluorobenzoyl)an ino]ethyl3-N-hydroxy-3-(3-hydroxypropyl)- 2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide, 3k) α-[2-[(3,4-Difluorobenzoyl)amino]ethyl3-N-hydroxy-3-(2-hydroxyethyl)- -oxo- l-(2-phenylethyl)-3-pyrroUdineacetamide, or 31) [R-(R*,S*)3-α-[2-[(3-Fluorobenzoyl)amino3ethyl3-N : hydroxy-3-(3- hydroxypropyl)-2-oxo-l-(2-phenylethyl)-3-pyrroUdineacetamide. 14. A method of inhibiting excess matrix metaUoproteinase which comprises administering to a patient in need thereof an effective amount of a compound of claim 1. 15. A method of claim 14 wherein matrix metalloproteinases comprises coUagenases, stromelysins, or gelatinases. 16. A method of treating a human, suffering from or susceptible to a diseases involving connective tissue degradation which comprises administering to a patient in need thereof an effective amount of a compound of claim 1. 17. A method of 16 wherein the diseases related to connective tissue degradation is osteoarthrits, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, or gastric ulceration. 18. A pharmaceutical composition which comprises an amount of the compound of claim 1 effective to inhibit excess matrix metaUoproteinase and a pharmaceuticaUy acceptable carrier. 19. The method of claim 14 wherein the effective inhibitory amount of the compound of claim 1 is administered oraUy, parenterally, or topicaUy in a pharmaceutical composition. 20. The method of claim 16 wherein the effective amount of the compound of claim 1 is administered oraUy, parenteraUy, or topicaUy in a pharmaceutical composition. 21. The method of claim 14 or 16 wherein said compound is administered in an amount of from about 0.1 to about 100 mg/kg of body weight day.

Inventors: JACOBSEN E JON, JACOBSEN, E., JON
Applicants: JACOBSEN E JON, UPJOHN CO, JACOBSEN, E., JON, PHARMACIA & UPJOHN COMPANY
Application year: 1997
Main classification: C07D207
IPC codes: A61K31, A61P1, A61P19, A61P29, A61P35, A61P43, C07D207, C07D231, C07D233, C07D401, C07D403, C07D409, C07D417