PEPTIDE ANALOGS

Abstract: A genus of novel peptide analogs which have potent renin-inhibiting activity, methods of treating renin-based hypertension using these compounds, and pharmaceutical compositions containing these compounds as active ingredients.

Description: I PEP IDE ANALOGS Technical Field The present invention relates to novel organic compounds which inhibit renin, processes for making such compounds, synthetic intermediates employed in these processes and methods of treating hypertension with such compounds. Background Art Renin is a proteolytic enzyme synthesized and stored principally in a specific part of the kidney called the juxtaglomerular apparatus. Any of three different physiologic circumstances may cause the release of renin into the circulation: (a) a decrease in the blood pressure entering or within the kidney itself; (b) a decrease in the blood volume in the body; or (c) a fall in the concentration of sodium in the distal tubules of the kidney. When renin is released into the blood from the kidney, the renin-angiotensin system is activated, leading to vasoconstriction and conservation of sodium, both of which result in increased blood pressure. The renin acts on a circulating protein, angiotensinogen, to cleave out a fragment called angiotensin I (Al). Al itself has only slight pharmacologic activity but, after additional cleavage by a second enzyme, angiotensin converting enzyme (ACE), forms the potent molecule angiotensin II (All). The major pharmacological effects of All are vasoconstriction and stimulation of the adrenal cortex to release aldosterone, a hormone which causes sodium retention. All is cleaved by an aminopeptidase to form angiotensin III (AIII), which compared to All, is a less potent vasoconstrictor but a more potent inducer of aldosterone release. Inhibitors of renin have been sought as agents for control of hypertension and as diagnostic agents for identification of cases of hypertension due to renin excess. With these objectives in mind, the renin- angiotension system has been modulated or manipulated, in the past, with ACE inhibitors. However, ACE acts on several substrates other than angiotensin I (Al), most notably the kinins which cause such undesirable side effects as pain, "leaky" capillaries, prostaglandin release and a variety of behavioral and neurologic effects. Further, ACE inhibition leads to the accumulation of Al . Although Al has much less vaso¬ constrictor activity than All, its presence may negate some of the hypotensive effects of the blockade of All synthesis. Inhibition of other targets in the renin- angiotensin system such as All with compounds such as saralasin can block All activity, but would leave unimpaired and perhaps enhance the hypertensive effects of AllI. On the other hand, there are no known side effects which result when renin is inhibited from acting on its substrate. Considerable research efforts have thus been carried out to develop useful inhibitors of renin. Past research efforts have been directed to renin antibodies, pepstatin, phospholipids and substrate analogs such as tetrapeptides and octapeptides to tridecapeptides. These inhibitors either demonstrate poor activity in inhibiting renin production or poor specificity for inhibiting renin only. However, Boger et al. , have reported that statine-containing peptides possess potent and specific renin-inhibiting activity (Nature. Vol. 303, p. 81, 1983). In addition, Szelke and co-workers have described polypeptide analogs containing a non-peptide link (Nature, Vol. 299, p. 555, 1982) which also cause potent renin inhibition and show a high specificity for this enzyme. Disclosure of the Invention In accordance with the present invention, there are renin inhibiting compounds of the formula: wherein A is hydrogen; loweralkyl; arylalkyl; OR, Q or SR 2Q wherein R 20 is hydrogen, loweralkyl or aminoalkyl; NR 21 R 22 wherein 21 and 22 are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; wherein B is NH, alkylamino, S, 0, CH 2 , NHCH 2 or CHOH and R 23 is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxy- alkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl) (alkyl)amino, [(dialkyl- amino)alkyl] ( lkyl)amino, (dihydroxyalkyl) (alkyl)amino, carboxyalkyl, aminoalkyl, N-protected aminoalkyl, alkyl- aminoalkyl, alkoxycarbonylalkyl, (N-protected) (alkyl)- aminoalkyl, dialkylaminoalkyl, (heterocyclic)alkyl or a substituted or unsubstituted heterocyclic; W is C=0 or CHOH; U is CH 2 or NR 2 , provided that when W is CHOH then U is CH 2 ; R, is loweralkyl, cycloalkylmethyl, benzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl) ethyl, (2-naphthyl)methyl, (4-imidazoyl)methyl, 4-hydroxy- benzyl, <* , ~J- -dimethylbenzyl, 1-benzyloxyethyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R. is phenoxy, thiophenoxy or anilino, B is CH, or CHOH or A is hydrogen; 3 is loweralkyl, loweralkenyl, [(alkoxy)alkoxy]loweralkyl, (thioalkoxy)alkyl, benzyl or heterocyclic ring substituted methyl; R 4 is ? ■ R 6 " OH R 6 Rl7 wherein R g is hydrogen or loweralkyl ; is loweralkyl, cycloalkylmethyl, benzyl, or CH 2 R 24' where R, 24 is selected from l,3-dioxan-2-yl; l,3-dioxolan-2-yl, l,3-dithiolan-2-yl or 1,3-dithian- 2-yl; R 7' ^8 and R Q are hydrogen or loweralkyl' and may be the same or different; V is NH, 0, S, SO, S0 2 , or CH 2 ; R 1Q is loweralkyl, cycloalkyl, cycloalkyl- alkyl, aryl, arylalkyl or an N-protecting group, or V and R 10 taken together are N 3 ; with the proviso that 10 may be an N-protecting group only when V is NH; "13 is CHOH or CO; "1 is CH 2' CF, or CF with the proviso that when R 13 "is CO',. "14 * is β "R1,5 is C C H H „,' C C H H R R , 25 wherein R 25 is loweralkyl, cycloalkyl, σycloalkylalkyl, aryl or arylalkyl, or R 14 and R 15 taken together can be with the proviso that when Λ 14 is CF, 2' '15 is CH 2 ; M is 0, S, SO, S0 2 , NR 26 wherein "26 is hydrogen or loweralkyl, NR 27 S0 2 or R 27 C0 wherein R 27 is hydrogen or loweralkyl, or M and "10 taken together are N 3.,;' R, 16,. is CH 2' CF 2 or" CH'R"4, 5 where R, is loweralkyl, hydroxy, hydroxyalkyl, alkoxy, allyl, alkaryloxy or thioalkyl χ7 is hydrogen or loweralkyl; R ιg is loweralkyl or lipophilic or aromatic amino acid side chains; P is- hydrogen, loweralkyl or -CH 2 0R 2a , wherein R 2 _ is hydrogen, loweralkyl or alkaryl; R,. is hydrogen or hydroxy; n is 0 or 1; when n is 0, T is alkylidene or alkylidene oxide; when n is 1, S is hydrogen or hydroxy and T is loweralkyl, hydroxyalkyl, aminoalkyl, haloalkyl, or azidoalkyl; R, g is hydrogen or loweralkyl; R 12 is hydrogen, loweralkyl, alkyl- cycloalkyl, ' arylalkyl, aminoalkyl, dialkyla inoalkyl; and pharmaceutically acceptable salts thereof. The chiral centers of the compounds of the invention may have either the "R" or "S" configuration but preferably have an "S" configuration except where noted. The terms "S" and "R" configuration are as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13-30. The term "N-protecting group" or "N-protected" as used herein refers to those groups intended to protect nitrogen atoms against undesirable reactions during synthetic procedures or to prevent the attack of exopeptidases on the final compounds or to increase the solubility of the final compounds and includes but is not limited to acyl, acetyl, pivaloyl, t-butylacetyl,. t-butyloxycarbonyl(Boc) , benzyloxycarbonyl (Cbz) or benzoyl groups or an L- or D-aminoacyl residue, which may itself by N-protected similarly. The term "loweralkyl" as used herein refers to straight or branched chain alkyl radicals containing from 1 to 7 carbon atoms including but not limited to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, 2-methylhexyl, n-pentyl, 1-methylbutyl, 2,2-dimethylbutyl, 2-methylpentyl, 2,2-dimethylpropyl, n-hexyl and the like. The term "arylalkyl" as used herein refers to an unsubstituted or substituted aromatic ring appended to an alkyl radical including but not limited to benzyl, 1- and 2-naphthylmethyl, halobenzyl and alkoxybenzyl . The term "alkylamino" as used herein refers to a loweralkkyl radical appended to an NH radical . The term "cycloalkyl" as used herein refers to an aliphatic ring having 4 to 7 carbon atoms. The term "cycloalkylmethyl" as used herein refers to a cycloalkyl group appended to a methyl radical, including but not limited to cyclohexylmethyl. The term "aryl" as used herein refers to a substituted or unsubstituted aromatic ring including but not limited to phenyl, naphthyl, halophenyl and alkoxy- phenyl. The term carboxyalkyl as used herein refers to a carboxylic acid group (-COOH) appended to a loweralkyl radical. The terms "alkoxy" and "thioalkoxy" as used herein refer to R29° ~ an< -~ R 2 9 S ~' respectively, wherein R 2g is a loweralkyl group. The term "arylalkoxy" as used herein refers to an aryl appended to an alkoxy radical. The term "arylalkoxyalkyl" as used herein refers to an aryalkoxy appended to a loweralkyl radical. The term "dialkylamino" as used herein refers to -N 3Q 31 wherein R 3Q and R 31 are independent¬ ly selected from loweralkyl groups. The term "N-protected aminoalkyl" as used herein refers to NH - 2 is appended to a loweralkyl group, where R 32 is an N-protecting group. The term "(heterocyclic)alkyl" as used herein refers to a heterocyclic group appended to a loweralkyl radical, including but not limited to imidazoylalkyl . The term alkoxycarbonylalkyl as used herein refers to R 33 C=OR 3 . , wherein R__ is an alkoxy group and 34 is loweralkyl. The terms "alkenyl" and "alkenyloxy", as used herein refer to R 35 ~ anc:i R 35°~' respectively wherein R 35 is an unsaturated alkyl group. The term "hydroxyalkoxy" as used herein refers to -OH appended to alkoxy radical. The term "dihydroxyalkoxy" as used herein refers to an alkoxy radical which is disubstituted with -OH radicals. The term "(hydroxyalkyl) (alkyl)amino" as used herein refers to -NR 3_6-R3,_7 wherein R3-6- is hydroxyalkyl and R 37 is loweralkyl. The term "(dihydroxyalkyl)(alkyl)amino" as used herein refers to -N 3a R 3g wherein R 3g is dihydroxyalkyl and R 3g is loweralkyl. The term "dihydroxyalkyl" as used herein refers to a loweralkyl radical which is disubstituted with -OH radicals. The term "((dialkylamino)alkyl)(alkyl) mino" as used herein refers to -NR 4. n 0R4.1, wherein R4.0- is an alkyl radical which is substituted with a dialkylamino radical and .. is loweralkyl. The term "carboalkoxyalkyl" as used herein refers to a loweralkyl radical which is substituted at any position with one or more carboalkoxy groups and includes but is not limited to carboalkoxymethyl, carboalkoxyethyl, carboalkoxypropyl, carboalkoxybutyl and carboalkoxypentyl. The term "carboalkoxy group" as used herein refers to an acyl radical which has appended to it an alkoxy group and includes but is not limited to methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, butyloxycarbonyl, isobutyloxy- carbonyl and t-butyloxycarbonyl. The term "alkylaminoalkyl" as used herein refers to NHR. 2 appended to a loweralkyl radical, wherein R. 2 is a loweralkyl group. The -term "(N-protected) (alkyl)aminoalkyl" as used herein refers to N 32 R 42 , which is appended to a loweralkyl radical, wherein R_ 2 and R. 2 are as defined above. The term "dialkylaminoalkyl" as used herein refers to NR «R appended to a loweralkyl radical wherein R. 3 and R.. are independently selected from loweralkyl. The term "(thioalkoxy)alkyl" as used herein refers to thioalkoxy appended to a loweralkyl radical. The term "aminoalkyl" as .used, herein refers to -NH 2 appended to a loweralkyl radical. The term "heterocyclic ring" or "heterocyclic" as used herein refers to any 5-, 6-, 9- or 10-membered ring containing from one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; having various degrees of unsaturation; wherein the nitrogen and sulfur heteroatoms may optionally be quaternized; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring. Heterocyclics in which nitrogen is the heteroatom are preferred. Fully saturated heterocyclics are also preferred. Preferred heterocyclics are: pyrryl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazo- linyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazo- lidinyl, pyridyl, piperidinyl, pyrazinyl, piperazinyl, " pyrimidinyl, pyridazinyl, morpholinyl, . thiazolidinyl, thiazolyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothi- azolyl, benzoxazolyl, furyl, thienyl and benzothienyl . Saturated heterocyclics may be unsubtituted or mono- or di-substituted with hydroxy, oxo, amino, alkyl¬ amino, dialkylamino or loweralkyl. Unsaturated heter¬ ocyclics may be unsubstituted or monosubstituted with hydroxy, amino, alkylamino, dialkylamino or loweralkyl. The most preferred heterocyclics are as follows .n wherein n is 1 or. 2 and X is N, NH, O, S, provided that X is the point of connection only when X is N, wherein Y is NH, N-loweralkyl, 0, S, or SO 2 , or wherein Z χ is N, 0, or S and not the point of connection and Z 2 is N when it is the point of connection and NH, 0 or S when it is not the point of connection. The terms "lipophilic or aromatic amino acid side chains" as used herein refers to those amino acid side chains which have an affinity for lipids or have an aromatic ring and include but are not limited to benzyl, isobutyl, isopropyl, sec-butyl, imidazol-4-yl- methyl, p-hydroxybenzyl , 1- and 2-naphthylmethyl, (pyrazolyl)- methyl, (thiazolyl)methyl, and cyclohexylmethyl . The term "hydrophilic amino acid side chain" as used herein refers to those amino acid side chains which have an affinity for water and include but are not limited to, those of serine, threonine, allothreonine, homoserine, cysteine, ornithine, arginine, and glutamine. General reference to amino acid side chains in both the description and claims herein is to be taken as reference to such, whether naturally occurring in protein or not, and to both D- and L-forms. The term "alkylidene" used herein refers to a straight or branched chain alkyl radical which is attached via a carbon-carbon double bond and includes but is not limited to methylidene, ethylidene, 1-propyl- idene, 1-butylidene, 1-pentylidene, 2-propylidene, 2-butylidene, 2-pentylidene, 3-pentylidene, 3-hexyl- idene, 3-heptylidene, and 4-heptylidene. The term "alkylidene oxide" used herein refers to an epoxide moiety which is derived from an alkylidene group. The terms "thioalkyl, haloalkyl or azidoalkyl" used herein refer to an alkyl radical which has appended to it a thio, halo or azido radical, respectively. The terms "Ala", "His", "Leu", "Phe", "Tyr", "Cys", "Gly", "Lys", Sar", "Ser", "Thr" and "Pro" as used herein refer to alanine, histidine, leucine, phenylalanine, tyrosine, cysteine, glycine, lysine, sarcosine, serine, threonine, and proline, respectively. The following examples will serve to further illustrate preparation of novel compounds of the present invention. Example 1 (3S, S)-4-t-Butyloxycarbonylamino- 3-hydroxy-6-methyl-l-heptene To a rapidly stirred -78°C solution of Boc- leucinal (1.5 g, 6.97 mmol) in anhydrous tetrahydrofuran (THF) (10 mL) was added a -78°C solution of vinyl magnesium bromide (7 mmol) in anhydrous THF (40 mL) dropwise over the course of 15 min; 2 h later the mixture was acidified to pH 7. The organic phase was separated, washed with brine (2 x 10 mL) and dried (Na-SO.). Filtration and evaporation provided an oil which was purified by flash chromatography on silica gel with 7/3 hexane-ether. There was obtained 3.9 (53%) of product, m.p. 57-59°C. Anal. calcd. for C 13 H 25 0 3 : C, 64.17; H, 10.36; N, 5.76. Found: C, 64.19; H, 10.13; N, 5.66. Example 2 (S)-Isobutyl-5(S)-vinyl-2-oxazo1idinone To a solution of (3S,4S)-4-t-butyloxycarbonyl- amino-3-hydroxy-6-methyl-l-heptane (10.5 g, 0.043 mol) in dimethylformamide (DMF) (100 mL) was added sodium hydride (2.4 g of 50% dispersion) portionwise at 0-5°C. After stirring for 20 h at room temperature, the reaction mixture was poured into cold aqueous NaCl solution. The resulting mixture was extracted with methylene chloride and the organic phase was washed several times with brine solution. Drying over MgSO. and evaporation gave a residue which was flash chromato- graphed on silica gel eluting with hexane/ethyl acetate mixtures. There was obtained 5.7 g (78%) of the desired compound as an oil. NMR (300 MHz, CDC1 3 , ppm) : 0.9 (2d,6H), 1.35-1.75 (m,3H), 3.6 (m,lH), 4.55 (t,lH), 5.4 (m,2H), 5.9 (m,lH). Example 3 4(S)-Isobutyl-5(S)-(2-mesyloxyethy1)-2-oxazolidinone To a 0°C solution of 4(S)-isobutyl-5(S)-vinyl- 2-oxazolidinone (4.7 g, 0.028 mol) in THF (20 mL) was added 9-BBN [9-borabicyclo-(3.3. Dnonane, 75 L, 0.0375 mol in THF] by dropwise addition. After stirring for 5 h at room temperature, the reaction was quenched by the addition of water (1 mL) . A solution of NaOH (6.7 g) in water (21 L) was then added followed by careful addition of H 2 0 2 (18 mL of 30%). The resulting mixture was heated at 65°C for 1 h, the THF was partially evaporated and the residue was distributed between ethyl acetate and brine solution. The organic phase was washed with brine solution and dried over MgSO.. Evaporation of the solvent gave a residual oil which was flash chromatographed on silica gel eluting with 5% MeOH in methylene chloride. The pure fractions were combined and evaporated to give 4.62 g of 4(S)-iso- butyl-5(S)-(2-hydroxyethyl)-2-oxazolidinone. A solution of this material (3.95 g, 0.021 mol) and triethylamine (3.2 g, 0.032 mol) in methylene chloride (40 mL) was cooled to 0°C and treated by dropwise addition with mesyl chloride (2.89 g, 0.025 mol). After stirring for 1 h at 0-5°C, the methylene chloride was washed successively with 0.5 N HC1, aqueous NaHC0 3 and brine solution. The organic solution was dried and evaporated to a solid product. Recrystallization . from hexane/ methylene chloride gave 3.9 g (70%) of product, m.p. 99-100°C. Anal. calcd. for C 10 H ιg NO 5 S: C, 45.27; H, 7.22; N, 5.28. Found: C, 45.38; H, 7.18; N, 5.23. Example 4 (S)-Isobuty1-5(S)-C2-(phenethylmercapto)ethyl]- 2-oxazolidinone To a 0°C solution of 4(S)-isobutyl-5(S)- (2-mesyloxyethyl)-2-oxazolidinone (500 mg, 1.88 mmol) and phenethyl mercaptan (273 mg, 1.98 mmol) in THF (6 mL) was added NaH (95 mg, 1.98 mmol of a 50% dispersion) all at once. The eaction was stirred for 3 h at room temperature and then distributed between methylene chloride and brine solution. The organic layer was washed with brine solution, dried over MgS0 4 and evaporated. The residue was chromatographed on silica gel eluting with 65/35 hexane/ethyl acetate to give 570 mg- (98%) of product as an oil. Anal. calcd. for C 17 H 25 N0 2 S: C, 66.41; H, 8.20; N, 4.56. Found: C, 66.60; H, 8.32; N, 4.58. Example 5 4(S)-Isobutyl-5(S)-[2-(isoamylmercapto)ethyl]- 2-oxazolidinone Using the procedure of Example 4 but changing phenethyl mercaptan to isoamyl mercaptan, gave the desired compound in 95% yield. Anal. calcd. for C 14 H 27 N0 2 S: C, 61.50; H, 9.95; N, 5.12.. Found: C, 61.19; H, 10.02; N, 5.00. Example 6 4(S)-Isobutyl-5(S)-[2-(isobutylmercapto)ethyl]- 2-oxazolidinone Using the procedure of Example 4 but changing phenethyl mercaptan to isobutyl mercaptan, gave the desired compound in 96% yield. Example 7 4(S)-Isobuty1-5(S)-[2-(isopropylmercapto)ethyl]- 2-oxazolidinone Using the procedure of Example 4 but changing phenethyl mercaptan to isopropyl mercaptan, gave the desired compound in 93% yield. Example 8 4(S)-Isobutyl-5(S)-[2-(phenethylsulfonyl)ethyl]- 2-oxazolidinone To a solution of 4(S)-isobutyl-5(S)-[2- (phenethylmercapto)-ethyl]-2-oxazolidinone (0.49 g, 1.59 mmol) in methylene chloride (6 L) was added 0.756 g (3.5 mmol) of m-chloroperoxybenzoic acid. After stirring for 1 h at room temperature, the methylene chloride solution was washed successively with aqueous NaHS0 3 and aqueous NaOH. The organic layer was dried and evaporated to a solid product. Trituration with hexane/ether (50/50) gave 495 mg (92%) of product, m.p. 100-101°C. Anal. calcd. for C 17 H 25 O.S: C, 60.15; H. 7.42; N, 4.13. Found: C, 60.27; H, 7.42; N, 4.00. Example 9 4(S)-Isobutyl-5(S)-[2-isoamylsulfonyl)ethyl]- 2-oxazolidinone Using the procedure of Example 8 with the resultant compound of- Example 5, gave the desired compound, m.p. 87-88°C. Anal. calcd. for C- 14.H o 2_7N04.S: C, 55.05; H, 8.91; N, 4.59. Found: C, 55.11; H, 9.31; N, 4.61. Example 10 (3S,4S)-4-Amino-3-hydroxy-6-methyl- 1-phenethylmercaptoheptane A solution of 4(S)-isobutyl-5(S)-[2-(phenethyl- mercapto)ethyl]-2-oxazolidinone (0.52 g, 1.69 mmol) and barium hydroxide octahydrate (1.06 g, 3.38 mmol) in dioxane (60 mL) and water (40 mL) was heated at reflux under 2 for 21 h. The solid barium carbonate was filtered and the filtrate was partially evaporated. The residue was diluted with water and the resulting solution was extracted with ether. The organic extract was washed with brine solution, dried over MgSO. and evaporated to a residue. Trituration with cold hexane gave 365 mg (77%) of product, m.p. 95-96°C. Anal. calcd. for C 16 H 27 NOS: C, 68.28; H, 9.67; N, 4.98. Found: C, 67.99; H, 9.66; N, 4.75. Example 11 (3S,4S)-4-Amino-3-hydroxy-l-isoamylmercapto- 6-methylheptane Using the procedure of Example 10 with the resultant compound of Example 5, gave the desired compound, m.p. 64-65°C. Anal. calcd. for C 13 H 2g NOS: C, 63.10; H, 11.81; N, 5.66. Found: C, 63.34; H, 12.09; H, 5.50. Example 12 (3S,4S)-4-Amino-3-hydroxy-6-methyl- 1-phenethylsulfonyIneptane Using the procedure of Example 10 with the resultant compound of Example 8, gave the desired compound, m.p. 153-154°C. Anal. calcd. for C 16 H 27 NO 3 S'H 2 0: C, 61.31; H, 8.68; N, 4.47. Found: C, 60.66; H, 8.63; N, 4.19. Example 13 (3S,4S)-4-Amino-3-hydroxy- l-isoamylsulfonyl-6-methylheptane Using the procedure of Example 10 with the resultant compound of Example 9, gave the desired compound, m.p. 125-126°C. Anal. calcd. for C. 3 H 2g N0 3 S: C, 55.88; H, 10.46; N, 5.01. Found: C, 55.75; H, 10.52; N, 4.65. Example 14 4(S)-Isobuty1-5(S)-(2-phenoxyethyl)-2-oxazo1idinone Using the procedure of Example 4 but changing phenethyl mercaptan to phenol and THF to DMF gave the desired compound in 54% yield. Mass spectrum: M + = 264. Example 15 (3S,4S)-4-Amino-3-hydroxy-6-methyl-l-phenoxyheptane Using the procedure of Example 10 with the resultant compound of Example 14, gave the desired compound as an oil in 82% yield. Mass spectrum: M = 238. Example 16 ... Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-6-methyl-l-phenethylmercaptoheptane To a stirred -12°C solution of Boc-Phe-Ala-OH (47.8 mg, 0.142 mmol) in anhyrous tetrahydrofuran (3 L) were added N-methylmorpholine (15.6 uL, 0.142 mmol) and iscbutylchloroformate (18.4 uL, 0.142 mmol) sequentially. After 3 min, a -12°C solution of the resultant compound of Example 10 (0.142 mmol) in anhydrous tetrahydrofuran (2 mL) was added. Ten minutes later, the mixture was allowed to warm to room temperature for 2 h, at which time the solvent was evaporated, and the resulting residue was partitioned between ethyl acetate (20 L) and saturated NaHC0 3 (5 mL) . The organic phase was washed sequentially with 0.01 M H 3 P0 ( 3 mL ) and brine (5 mL) . Drying (Na 2 SO.) and evaporating provided 77 mg (90%) of the desired compound as a glass. Anal. calcd. for C 33 H. g N 3 0 5 S: C, 66.08; H, 8.23; N, 7.00. Found: C, 66.11; H, 8.35; H, 6.84. Example 17 Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-l-isoamylmercapto-6-methylheptane Using the procedure of Example 16 with the resultant compound of Example 11, gave the desired compound, m.p. 137-138°C. Anal. calcd. for C 30 H 5] N 3 O 5 S: C, 63.68; H, 9.09; N, 7.43. Found: C, 64.01; H, 8.93; N, 7.39. Example 18 Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-6-methyl-l-phenethylsulfonylheptane Using the procedure of Example 8 with the resultant compound of Example 16, gave the desired compound, m.p. 186-187°C. Anal. calcd. for C 33 H 4g N 3 0-.S: C, 62.74; H, 7.82; N, 6.65. Found: C, 62.67; H, 7.56; N, 6.61. Example 19 Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-l-isoamylsulfonyl-6-methyIneptane Using the procedure of Example 8 with the resultant compound of Example 17, gave the desired compound. Anal. calcd. for C 30 H_.N 3 O 7 S: C, 60.27; H, 8.60; N, 7.03. Found: C, 60.47; H, 8.29; N, 6.98. Example 20 Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-l-isoamylfulfonyl-6-methylheptane Using the procedure of Example 8 but, using only one molar equivalent of m-chloroperoxybenzoic acid and conducting the reaction at 0°C, the resultant compound from Example 17 was converted to the desired compound. Example 21 Boc-Phe-Ala Amide of (3S,4S)-4-Amino- 3-hydroxy-6-methyl-l-phenoxyheptane Using the procedure of Example 16 with the resultant compound from Example 15, gave the desired compound. Example 22 Boc-Phe-His Amide of (3S,4S)-4-Amino-3-hydroxy- l-isoamylsulfonyl-6-methylheptane To a stirred -23°C solution of Boc-Phe-His-OH (153 mg, 0.38 mmol) in anhydrous dimethylforma ide (5 mL) was added a solution of the compound from Example 13 (0.38 mmol) in dimethylformamide (3 mL) . Hydroxybenzotriazole (HOBT, 77 mg, 0.57 mmol) and di- cyclohexylcarbodiimide (DDC, 78 mg, 0.38 mmol) were then added sequentially. After 2.5 h the mixture was warmed to 25°C, stirred 12 h, filtered and evaporated to a residue which was partitioned between ethyl acetate (20 mL) and saturated NaHC0 3 (8 mL) . The organic phase was then washed separately with saturated NaHC0 3 (8 mL) and brine (8 mL) . Drying (N 2 S0 4 ) and evaporating provided a white solid which was chromato¬ graphed on Si0 2 (95/5, dichloromethane/ methanol) to give 180 mg (75%) of the desired compound. Mass spectrum: (M+H) + = 664. Example 23 Boc-Phe-His Amide of (3S,4S)-4-Amino- 3-hydroxy-6-methyl-l-phenethylsulfonylhep ane Using the procedure of Example 22 with the resultant compound of Example 12, gave the desired compound. Anal. calcd. for C 36 H 5] N 5 0 7 S: C, 61.96; H, 7.37; N, 10.03. Found: C, 61.38; H, 7.71; N, 9.07. Example 24 (5S,6S)-5-Acetoxy-6-t-butyloxycarbonylamino- 8-methyl-l-nonene Using the procedure of Example 1 but changing vinyl magnesium bromide to butenyl magnesium bromide, gave a 56% yield of (5S,6S)-6-t-butyloxycarbonylamino- 5-hydroxy-8-methyl-l-nonene as an oil. A 25 g (0.092 mol) sample of this material was dissolved in methylene chloride (200 mL) containing 10 mL of pyridine. Acetic anhydride (11.74 g, 0.115 mol) was added by dropwise addition and the resulting mixture was stirred for 24 h at room temperature. The mixture was washed successively with aqueous NaHC0 3 , aqueous citric acid and brine solution. After drying over MgS0 4 , the solvent was evaporated to a residue. Flash chromatog- raphy on silica gel gave an 82% yield of product as an oil. Anal. calcd. for C 17 H 3] N0 4 : C, 65.15; H, 9.97; N, 4.47. Found: C, 65.11; H, 9.66; N, 4.30. Example 25 4(S)-Isobutyl-5(S)-(4-butenyl)-2-oxazolidinone A solution of the compound from Example 24 (33 g, 0.105 mol) dissolved in 150 mL of dimethylform¬ amide and 50 mL of tetrahydrofuran was treated with 11 g (0.204 mol) of sodium methoxide in one portion. The reaction mixture was stirred overnight at room temperature and then poured into an acidified solution of aqueous NaCl with cooling. The resulting mixture was extracted with ether. The ethereal extract was washed three times with brine solution and dried over MgSO.. Evaporation of the solvent gave 19.6 g (95%) of liquid product. - Anal. calcd. for *u H ιg N0 2 : C ' 66.97; H, 9.71; N, 7.10. Found: C, 67.25; H, 9.84; H, 6.91. Example 26 4(S)-Isobutyl-5(S)-(2-formylethyl)-2-oxazolidinone To a stirred solution of the compound from Example 25 (5.0 g, 25.2 mmol) in dichloromethane (60 mL) was added m-σhloroperbenzoic acid (MCPBA, 10.8 g of 80% MCPBA, 50 mmol). After 68 h the reaction mixture was cooled to 0°C, and 0°C 10% Na 2 S0 3 was added with stirring. After 15 min, the solid was filtered off and extracted with dichloromethane. The combined organic phase was washed sequentially with 0°C 10% a 2 S0 3 , saturated NaHC0 4 and water. Drying (MgS0 4 ), filtering and evaporating provided crude epoxide which was chromatographed on silica gel eluting with 50/50 hexane-ethyl acetate to give a 73% yield of purified epoxide. A 10 g (0.047 mol) sample of the above epoxide was mixed with 200 mL of 6% perchloric acid and kept for 24 h at room temperature. The solution was neutralized with solid sodium bicarbonate, saturated with sodium chloride and extracted with ethyl acetate. Evaporation of the solvent left 10 g of glycolic material as a viscous syrup. The above glycol (10 g, 0.043 mol) was dissolved in 150 mL of water and treated all at - once with a solution of periodic acid (9.1 g, 0.04 mol) in 150 mL of water. After stirring at 25°C for 5 h, the mixture was extracted with methylene chloride. The dried methylene chloride solution was evaporated to give a quantitative yield of product. Example 27 4(S)-Isobuty1-5(S)-(6-methy1-3-oxoheptyl)- 2-oxazolidinone A 2 g (0.01 mol) portion of the compound from Example 26 was dissolved in THF (50 mL) and treated at 0-5°C with 37.5 mL of an 0.8 M solution of isopentyl magnesium bromide in THF. The reaction was stirred for 2 h at room temperature and then poured into ice water which contained 6.5 mL of 6 * N HC1. The mixture was extracted with methylene chloride. Evaporation of the dried methylene chloride solution gave a quantitative yield of the Grignard adduct. This material was dissolved in 300 mL of acetone and treated by dropwise addition with Jones solution until the orange color persisted. The chromium salts were filtered and the filtrate was evaporated. The residue was diluted with ether and the resulting solution was washed successively with aqueous NaHC0 3 and brine solution. After drying over MgSO the solvent was evaporated to give 1.7 g (66%) of product as an oil. NMR (300 MHz, CDC1 3 , ppm) : 0.86-0.96 (m,12H), 2.41 (m,2H), 2.67 (m,2H), 3.5 (m,lH), 4.15 (m,lH) . Example 28 (S)-Isobuty1-5(S)-(6-methyl-3-oxohepty1)- 2-oxazolidinone Ethylene Ketal A mixture of the product from Example 27 (2.5 g, 9.3 mmol), ethylene glycol (7.5 mL) and p-toluenesulfonic acid (60 mg) in toluene (100 L) was heated at reflux with a Dean-Stark trap for 8 h. The cooled mixture was washed with aqueous NaHCO- and dried over MgS0 4 . Evaporation of the solvent gave a residue which was flash chromatographed on silica gel eluting with 65/35 hexane-ethyl acetate to give 2.3 g (79%) of product. NMR (300 MHz, CDC1 3 , pp ) : 0.85-0.95 (4d,12H), 3.5 (m.lH), 3.95 (s,4H), 4.15 (m-lH). Example 29 (4S,5S)-4-Amino-2,1l-dimethyl-5-hydroxy- 8-oxododecane Ethylene Ketal Using the procedure of Example 10 with the resultant compound of Example 28, gave the desired compound in 73% yield, m.p. 26°C. Example 30 Boc-Phe-Ala>Amide of (4S,5S)-4-Amino- 2,ll-dimethyl-5-hydroxy-8-oxododecane Using the procedure of Example 16 with the resultant compound of Example 29, gave a 90% yield of the title compound as the corresponding ethylene ketal . Anal. calcd. for C 33 H 55 3 0 7 : C, 65.43; H, 9.15; N, 6.94. Found: C, 65.28; H, 9.16; N, 6.67. The desired deketalized product was obtained as follows. A solution of the ketal (400 mg) was stirred for 24 h in 37 mL acetic acid/water/tetrahydrofuran (3/1/1) . The solvents were evaporated under reduced pressure and the residue was triturated with hexane- ether (65:35) to give 280 mg (76%) of product; m.p. 137-138°C. Anal. calcd. for C 31 H 51 N 3 O g : C, 66.28; H, 9.15; N, 7.48. Found: C, 66.29; H, 9.23; N, 7.32. Example 31 Boc-His Amide of (3S,4S)-4-Amino-3-hydroxy- 6-methyl-l-phenethylsulfonylheptane Using the procedure of Example 22 with the resultant compound of Example 12 and Boc-His-OH rather than Boc-Phe-His-OH, gave the desired compound. Example 32 [ (4-Morpholinyl)carbonyl]-Phe Methyl Ester A suspension of L-phenylalanine methyl ester hydrochloride (6 g) in toluene (125 mL) was heated to 100°C while phosgene gas was bubbled into the reaction mixture. After approximately 1.5-2 h, the mixture became homogeneous. The passage of phosgene was continued for an additional 15 min, keeping the temperature at 90-100°C. The toluene was then evaporated and the residue chased several times with benzene. A 6.5 g (0.03167 mol) sample of -isocyanato- L-phenylalanine methyl ester was dissolved in 50 mL of methylene chloride and cooled to 0°C. Mσrpholine (2.76 mL, 0.03167 mol) dissolved in 5 mL of methylene chloride was added dropwise. After 10 min at 0-5°C, the reaction mixture was distributed between 0.5 N HC1 and methylene chloride. The organic layer was washed with aqueous NaHC0 3 and dried over MgS0 4 . Evaporation of the solvent gave 7 g of product after trituration with hexane, m.p. 90-91°C. Example 33 C (4-Morpholinyl)carbonyl]-Phe-QH To a 0°C solution of the product from Example 32 (3.63 mmol) in dioxane (15 mL) was added a solution of lithium hydroxide (0.174 g, 4.15 mmol) in water (7.5 mL). After stirring for 1 h at 0-5°C, the reaction mixture was diluted with cold water ' and extracted 2X with ether. The aqueous portion was acidified with 6N HC1 and extracted with ether. The organic extract was washed with brine and evaporated to give an 87% yield of product as a viscous liquid. Example 34 Boc-(Me)His Amide of (3S,4S)-4-Amino- 3-hydroxy-6-methyl-l-phenethylsulfonyl Heptane To a stirred solution of N -(t-butyloxy- carbonyl)-N -methyl-N ιm -tosyl-L-histidine [J. Med. Chem. 29, 2088 (1986), 9.15 mmol] and the product from Example 12 (6.1 mmol) in dichloromethane (75 mL) was added 1.28 mL (9.18 mmol) of triethyl mine, followed by the slow addition of diethoxyphosphoryl cyanide (1.36 mL, 8.87 mmol). After being stirred at room temperature for 16 h, the reaction mixture was diluted with dichloromethane and then washed with saturated aqueous NaHCO- . The organic phase was dried (MgS0 4 ) and then concentrated. The residue was chromatographed on silica gel eluting with ethyl acetate/hexane mixture to give a 75% yield of coupled product. The above product was stirred in CH 3 0H with 5 equiv. HOBT for 16 h. The reaction mixture was filtered. The filtrate was evaporated to solid which was taken up with CHC1 * 3 , washed with dil NaHCO.,. brine, dried and filtered. The resultant residue after evaporation was chromatographed eluting with 5% CH 3 0H/CHC1 3 . The desired product was obtained in 60% yield. Example 35 C (4-Morpholinyl)carbonyl]-Phe-(Me)His Amide of (3S,4S)-4-Amino-3-hydroxy- 6-methyl-l-phenethylsulfonylheptane The product from Example 34 was deprotected with trifluoroacetic acid/methylene chloride (1:1) and the resultant amine coupled to the product from Example 33 using the method of Example 34. There was obtained a 50% yield of the title compound. Example 36 3-3enzyloxycarbonylamino-3-methylbutanoic Acid A solution of - 2,2-dimethyl-3-carbomethyoxy- propionic acid [LeMaul, Bull. Soc. Chim. Fr■ , 828 (1965), 20 g, 0.125 mol], diphenylphosphorylazide (34.3 g, 0.125 mol) and triethylamine was heated in toluene (150 mL) at 100°C for 2 h. After cooling to 5°C, the toluene solution was washed successively with 0.5 M HC1, aqueous NaHCO., and brine. Evaporation of the dried solution gave a residue which was chromato¬ graphed on silica gel eluting with 60/40 hexane/ether. There was obtained 13 g of methyl 3-isocyanato-3-methyl- butanoate as a mobile liquid. A solution of this material in toluene (20 L) was treated with benzyl alcohol (13 mL) and the resulting mixture heated at reflux for 40 h. Evaporation of the toluene left a residue which was dissolved in ethanol (125 mL) and then treated with a solution of NaOH (6.6 g, 0.165 mol) in 22 mL of water. After 5 h, the reaction mixture was partially evaporated, washed with ether and acidified with 6N HC1. Extraction with methylene chloride and evaporation gave 21 g of the desired product. 1-TMR (300 MHz, CDC1 3 ): 1.42 (s,6H), 2.78 (s,2H), 5.08 (s,2H). Example 37 Cbz-[ (β,β-di-Me)-β-Ala]-Phe-QCH 3 A 4.0 g sample of 3-benzyloxycarbonylamino- 3-methylbutanoic acid was coupled to phenylalanine methyl ester hydrochloride (3.43 g) using the mixed anhydride procedure described in Example 16. Purification of the crude product by flash chromatog- raphy eluting with 65/35 ether/hexane gave an 86% yield of product. NMR (300 MHz, CDC1 3 ): 1.32 (s,3H), 1.34 (S,3H), 2.46 (d,lH), 2.63 (d,lH), 2.98 (dd,lH), 3.09 (dd,lH), 3.70 (S,3H), 4.86 (dd.lH), 4.97 (d,lH), 5.2 (d,lH), 5.3 (S,1H), 6.13 (d,lH). Example 38 Cbz-[ (β,β-di-Me)-β-Ala3-Phe-OH To a 0°C solution of Cbz-C(β,β-di-Me)-β-Ala]- Phe-OMe (1.5 g, 3.63 mmol) in dioxane (15 mL) was added a solution of lithium hydroxide (0.174 g, 4.15 mmol) in water (7.5 mL) . After stirring for 1 h at 0-5°C, the reaction mixture was diluted with cold water and extracted 2X with ether. The aqueous portion was acidified with 6N HC1 and extracted with ether. The organic extract was washed with brine and evaporated to give an 87% yield of product as a viscous liquid. Example 39 Cbz-[(β,β-di-Me)-β-Al ]-Phe-His Amide of (3S,4S)- ■ 4-Amino-3-hydroxy-6-methyl-l-phenethylsulfonylheptane The product from Example 38 was coupled to the product from Example 31 using the procedure described in Example 22. There was obtained a 50% yield of the title compound. Example 40 H-[(β,β-di-Me)-β-Ala]-Phe-His Amide of (3S,4S)- 4-Amino-3-hydroxy-6-methyl-l-phenethylsulfonylheptane The resultant compound of Example 39 (0.2 g, 0.247 mmol) in acetic acid (5 mL) was hydrogenated at 1 atmosphere with 10% Pd/C (0.1 g) for 8 h. Filtration, extraction of the catalyst with acetic acid, and evaporation of the combined acetic acid solutions gave a residue which was dissolved in H 2 0 (10 mL) and lyopholized .to provide 75% of the desired product. Example 41 3-3enzyloxycarbonylamino-2,2-dimethylpropionic Acid 3-Carbomethoxy-3-methylbutanoic acid [Bull. Soc. Chi . F . , 828 (1965), 7.85 g, 0.049 mol] was reacted with diphenylphosphorylazide and triethylamine as described in Example 36. After heating the toluene solution for 1.5 h, benzyl alcohol (8 g) was added directly to the reaction mixture and heating at reflux was continued for 20 h. Work-up and chromatography gave methyl 3--benzyloxycarbonyl-amino-2,2-dimethylpropion- ate. NMR (300 MHz, CDC1 3 ): 1.2 (s,6H), 3.3 (d,2H), 3.68 (s,3H), 5.1 (s,2H), 5.22 (m,lH). A sample of the methyl ester (6.21 g, 0.023 mol) was saponified with 3.1 g (0.78 mol) of NaOH in 100 mL ethanol/10 mL H 2 0 at room temperature for 48 h. Work-up as in Example 36 gave the desired product as a liquid. NMR (300 MHz, CDC1 3 ): 1.23 (s,6H), 3.32 (d,2H), 5.10 (s,2H), 5.27 (m,lH) . Example 42 To a solution of 3-benzyloxycarbonylamino- 2,2-dimethylpropionic acid (1.5 g, 5.97 mmol) in methylene chloride (13 mL) was added oxalyl chloride (0.757 g, 5.97 mmol) and dimethylformamide (30 uL) . After stirring for 1 h at room temperature, the reaction mixture was cooled to 0°C and treated successively with OMe-tyrosine methyl ester hydrochloride (1.465 g, 5.97 mmol) and N-methylmorpholine (1.81 g, 17.9 mmol). Stirring for 1 h at 0-5°C was followed by distribution between CH 2 C1 2 and 0.5 N HC1. The organic phase was washed with aqueous NaHCO- and brine and dried over MgS0 4 . Evaporation of the solvent gave a residue which was purified by chromatography. There was obtained a 61.5% yield of product as a liquid. Example 43 Cbz-C , a-di-Me)- β -Ala]-(OMe)Tyr-QH To a 0°C solution of Cbz-[ ( a , a -di-Me)-β-Ala]- (OMe)-Tyr-OMe (1.2 g, 2.71 mmol) in dioxane (15 mL) was added a solution of lithium hydroxide (0.115 g, 2.75 mmol) in water (7.5 L) . After stirring for 1 h at 0-5°C, the reaction mixture was diluted with cold water and extracted 2X with ether. The aqueous portion was acidified with 6N HC1 and extracted with ether. The organic extract was washed with brine and evaporated to give an 87% yield of product as a viscous liquid. Example 44 H-[( a , a -di-Me)-β-Ala]-(OMe)Tyr-His Amide of (3S,4S)- 4-Amino-3-hydroxy-6-methyl-l-phenethylsulfonylheptane Using the procedures described in Examples 39 and 40, the product from Example 43 was converted to the desired product. Example 45 2(S)-C [ (4-Morpholinyl)carbonyl]oxy]- 3-phenylpropionic Acid Methyl Ester To L-phenyllactic acid methyl ester (3.2 g) was added 150 mL of 12.5% phosgene in toluene and 25 drops of dimethylformamide. After stirring for 16 h at room temperature, the solvent was evaporated and the residue chased several times with benzene. The resulting product was dissolved in methylene chloride (50 mL) , cooled to 0°C and treated by dropwise addition with 3.86 g (0.044 mol) of morpholine. The reaction mixture was stirred for 2 h at 0-5°C and then distributed between 0.5 N HC1 and methylene chloride. The organic phase was washed with aqueous NaHC0 3 and brine and evaporated to a residue. Flash chromatography on silica gel eluting with 2/1 ether-hexane gave a 65% yield of product. NMR (300 MHz): 3.08 (dd,lH), 3.20 (dd,lH), 3.8 (s,3H), 5.19 (dd,lH) . Example 46 2(S)-[ (4-Morpho1iny1)carbony1]oxy-3-phenylprO ionic Acid Using the hydrolysis procedure of Example 33, the title compound was obtained in 90% yield. Example 47 2(S)-[ (Morpho1iny1)carbony1]oxy-3-phenylpropionyl- His Amide of(3S,4S)-4-Amino-3-hydroxy- 6-methyl-l-phenethylsulfonylheptane Using the procedure of Example 22 with the resultant compound of Example 31 and the product from Example 46 rather than Boc-Phe-OH, gave the desired product. Example 48 3-t-Butyloxycarbonylamino-5-methylhex-l-ene To a stirred suspension of methyltriphenyl phosphonium bromide (10.97 g, 30.70 mmol) in anhydrous tetrahydrofuran (200 mL) at -78°C (dry ice/acetone bath) under an argon atmosphere, was added n-butyl lithium (19.8 mL of a 1.55 M hexane solution) dropwise over the course of 5 min. After 10 min, the -78°C bath was replaced with a 0°C bath for .5 h, at which time the resulting orange solution was cooled again to -78°C. The solution was then added dropwise by cannula to a stirred -78°C solution of Boc-leucinal (6.00 g, 27.91 mmol) in anhydrous tetrahydrofuran (30 mL) over the course of .5 h. The mixture was then allowed to warm to room temperature during a 3 h period after which water (150 mL) was added. Extraction with hexane (4 x 100 mL) provided a combined organic phase which was washed with brine (100 mL), dried (Na 2 S0 4 ), and concentrated to give crude 3-t-butyloxycarbonylamino-5-methylhex-l-ene (6.5 g) . Chromatography with ether/hexane (1/9) provided pure 3-t-butyloxycarbonylamino-5-methylhex- 1-ene (3.71 g, 60%). Mass spectrum: El, M + -57 = 156; CI, (M + H) + = 214. Example 49 3-t-Butyloxycarbonylamino-5-methyl-l,2-oxohexane To a stirred solution of 3-t-butyloxycarbonyl- amino-5-methylhex-l-ene (0.43 g, 2.0 mmol) in dichloro¬ methane (20 mL) was added m-chloroperoxybenzoic acid (MCPBA, 1.51 g of 80% MCPBA, 7.0 mmol). After 68 h the reaction mixture was cooled to 0°C, and 0°C 10%* a 2 S0 3 (5 mL) was added with stirring. After 15 min, the solid was filtered off and extracted with dichloromethane. The combined organic phase was washed sequentially with 0°C 10% Na 2 S0 3 (6 mL) , saturated NaHC0 3 (2 6 L) and water (5 L) . Drying (MgS0 4 ), filtering, and evaporating provided crude 3-t-butyl-oxycarbonylamino- 5-methyl-l,2-oxohexane (0.42 g) which was chromato¬ graphed on 50 g of Si0 2 (hexane/ether, 3/1) to give pure 3-t-butyloxycarbonylamino-5-methyl-l,2-oxohexane (0.27 g, 59%). Mass spectrum: M + = 229. Example 50 3-t-Butyloxycarbonylamino-l-cyclohexylmercapto- 2-hydroxy-5-methylhexane To a stirred solution of 3-t-butyloxycarbonyl- amino-5-methyl-l,2-oxohexane (200 mg, 0.87 mmol) in methanol (8.7 L) was added cyclohexyl mercaptan (102 mg, 0.87 mmol) and triethylamine (88 mg, 0.87 mmol). The resultant solution was refluxed for 2 h and then evaporated to give a residue which was chromatographed on 15 g of 40 u Si0 2 (7/3, hexane/ether) to give 281 mg (84%) of 3-t-butyloxycarbonylamino-l-cyclohexyl- mercapto-2-hydroxy-5-methylhexane. Mass spectrum: M •* ■ ** 345. Anal, calcd. : C, 62.6; H, 10.2; N, 4.0. Found: C, 62.9; H, 10.4; N, 3.9. Example 51 3-Amino-l-σyclohexylmercapto-2-hydroxy- 5-methylhexane Hydrochloride To a stirred solution of approximately 0.25 mmol of the resultant compound of Example 50 in methanol was added methanolic HCl (10 mL of approximately 0.75 M HCl). After 8 to 12 h, the solvent was evaporated, and the desired compound was used without further purification. Example 52 Boc-His Amide of 3-Amino- l-cyclohexylmercapto-2-hydroxy-5-methylhexane To a stirred suspens ion of Boc-His-OH ( 72 mg, 0 . 28 mmol ) in dry dimethylformamide ( 3 mL) at -23 °C was added a solution of 3-amino-l-cyciohexylmercapto- 2-hydroxy-5-methylhexane hydrochloride (derived from 98 mg, 0.28 mmol, of 3-t-butyl-oxycarbonylamino-l-cyclo- hexylmercapto-2-hydroxy-5-methylhexane using the procedure of Example 51) in dry dimethylformamide (2 mL) containing N-methylmorpholine (29 mg, 0.28 mmol). Hydroxybenzotriazole (HOBT, 58 mg, 0.43 mmol) and N,N'- dicyclohexylcarbodiimide (DCC, 59 mg, 0.28 mmol) were then added sequentially. After 2 h the mixture was allowed to warm to room temperature. After 22 h the mixture was filtered, evaporated, and partitioned between ethyl acetate (18 mL) and saturated aqueous NaHC0 3 (6 mL) . The layers were separated, and the organic phase was washed with brine (5 mL), dried (Na 2 S0 4 ), filtered, and evaporated to a solid which was chromatographed on Si0 2 (9/1, dichloromethane/ methanol) to give 86 mg (63%) of the desired compound. Mass spectrum: (M+H) = 483. Example 53 Boc-Phe-His Amide of 3-Amino- l-cyclohexylmercapto-2-hydroxy-5-methylhexane The resultant compound of Example 52 was treated with methanolic HCl according to the procedure used in Example 51, yielding the corresponding depro- tected HCl salt which was used as described below without further purification. To a stirred -12°C solution of Boc-Phe-OH (19.2 mg, 0.0725 mmol) in anhydrous tetrahydrofuran (3 mL) was added N-methyl¬ morpholine (8.0 1, 0.0725 mmol) in a dropwise fashion followed by isobutylchloroformate (9.4 1, 0.0725 mmol). After 3 min, a -12°C solution of the above HCl salt in anhydrous tetrahydrofuran (2 L) containing N-methyl¬ morpholine (16.0 1, 0.145 mmol) was added over the course of 30 sec. After 15 min, the mixture was allowed to warm to room temperature for 3 h at which time the solvent was evaporated, and the residue was partitioned between ethyl acetate (20 mL) and saturated NaHCO., (6 mL) . The layers were separated and the organic phase was washed with brine (5 mL) . Drying (Na 2 S0 4 ), evaporating, and chromatographing the resulting solid on Si0 2 (9/1, dichloromethane/methanol) provided 11 mg of the desired compound (24% yield). Mass spectrum: (M+H) + = 630. Example 54 (4 )-3-(3-Phenylpropiony1)- 4-(2-propyl)-oxazolidine-2-one To a stirred solution of 4-(2-propyl)- oxazolidine-2-one in anhydrous tetrahydrofuran (250 mL) under a nitrogen atmosphere at -78°C were added in a dropwise fashion a solution of -butyllithium in hexane (50 mL, 77.4 mmol) over 5 to 10 min. After stirring an additional 20 min at -78°C 3-phenylpropionyl chloride (12.7 mL, 85.2 mmol) was added neat. The reaction was warmed to room temperature and stirred 1 to 2 h at the temperature. The reaction was quenched by adding 100 mL of saturated aqueous ammonium chloride and the volatiles removed by rotary evaporation. The resulting aqueous residue was extracted three times with ether and the combined organic phases were washed with brine, dried (Na 2 S0 4 ), filtered and concentrated in vacuo. Recrystallization from hexanes/ethyl acetate provided the title compound (16.6 g, 82%). mp = 86.5 to 87.5°C. Mass spectrum: (M+NH 4 ) + = 279, (M+H) + = 262. Example 55 (4R)-3-[ (2-R)-2-(t-butyl acetyl)-3-phenylpropionyl]- 4-(2-propyl)-oxazolidine-2-one To a stirred solution of the product resulting from Example 54 (2.28 g, 8.72 mmol), in anhydrous tetra¬ hydrofuran (30 mL) under a nitrogen atmosphere at -78°C was added a solution of sodium hexamethyldisilylamide (9.6 mL, 9.59 mmol) in tetrahydrofuran. After stirring for 30 min at -78°C, t-butyl bromoacetate (2.21 g, 11.34 mmol) was added in anhydrous tetrahydrofuran and the resulting solution stirred 1 h at -78°C. The reaction was quenched by adding 20 mL of saturated aqueous ammonium chloride and partitioned between water and ether. The aqueous layer was drawn off and extracted with ether. The combined organic phases were washed with 10% aqueous HCl, saturated aqueous NaHC0 3 , and brine, dried (Na 2 S0 4 ), filtered, and concentrated in vacuo■ Recrystallization from acetone/hexanes provided the desired purified product (2.59 g, 79%). m.p. = 167-168°C. Mass spectrum: (M+NH 4 ) + = 393, (M+H) + = 376. Example 56 Benzyl (2R)-2-(t-butyl acetyl)-3-phenyl-proρionate To a stirred solution of dry benzyl alcohol (0.55 mL, 5.33 mmol) in anhydrous tetrahydron furan (18 mL) under a nitrogen atomosphere at 0°C was added a hexane solution of n-butyllithium (2.58 mL; 4.00 mmol). To this solution was added the product from Example 55 in anhydrous tetrahydrofuran (10 mL) . After stirring 1 h at 0°C the reaction was quenched by adding excess saturated aqueous ammonium chloride. The volatiles were removed by rotary evaporation and the resulting aqueous residue extracted two times with ether. The combined organic layers were washed with brine, dried (Na 2 S0 4 ), filtered, and concentrated in vacuo provided an oil which was purified by chromatography on Si0 2 (15% ethyl acetate/hexanes) to provide the desired product (0.89 g, 94%) as a colorless oil. Mass spectrum: (M) + = 354. Example 57 Benzyl (2R)-2-acetyl-3-phenylpropionate The product from Example 56 (0.52 g, 1.47 mmol) was dissolved in a 1:1 (v:v) solution (6 mL) of tri- fluoroacetic acid and dichloromethane and stirred at room temperature for 1 h. The volatiles were removed in vacuo to provide the title compound (0.437 g, 100%) as an oil which crystallized on standing. The unpurified material was of sufficient purity to employ in subsequent steps. Mass spectrum: (M) = 298.- Example 58 Benzyl-(2R)-2-benzyl- 3-(N-morpholinocarbamoyl)propiσnate The product from Example 57 (0.438 g, 1.47 mmol), diphenylphosphoryl azide (317 uL, 1.47 mmol), and triethylamine (205 uL, 1.47 mmol) in dry benzene (6 mL) were refluxed for 3 to 5 h to provide a solution of the derived isocyanate which was cooled to 0°C and treated with morpholine (141 uL, 1.62 mL) . The cooling bath was removed and the reaction stirred for 1 h. The reaction mixture was poured into 10% aqueous HCl and extracted two times with ether. The combined organic layers were washed successively with saturated aqueous NaHC0 3 and brine, dried (Na 2 S0 4 ), -filtered and concentrated in vacuo to provide the unpurified product. The desired product (0.403 g, 72%) was obtained in pure form after chromatography on Si0 2 (3% methanol/chloroform) as a thick oil which formed an amorphous solid on standing. Mass spectrum: (M) + = 382. NMR (300 MHz, C0C1 3 , pp , TMS as internal standard) 7.12-7.40 (m, 10H) , 5.18 (AB; J=12.6 Hz; 2H) , 4.8 (dd; J=5.7 Hz; 1H), 3.59 (d,d; J=6.0, 6.0 Hz; 4H) , 3.55 (d,d,d; J=3.0, 6.0, 14.4 Hz; 1H), 3.37 (d,d,d; J=5.4, 8.4, 14.4 Hz; 1H) , 3.13 (d,d; J=6.0, 6.0 Hz; 4H) , 2.8-3.10 (m, 3H) . Example 59 Benzyl (2R)-2-benzyl-3-(ethoxycarbamoyl)propionate The procedure as described in Example 58 was followed except absolute ethanol was employed in lieu of morpholine. Mass spectrum: (M) + = 341. NMR (300 MHz, CDC1 3 , ppm, TMS as internal standard) 7.1- 7.4 (m,10H), 5.17 (s,2H), 4.96 (br s,lH), 4.07 (d,d,d; J=6.6, 6.6, 6.6 Hz,2H), 3.25-3.5 (2 br ABX,2H), 2.9-3.05 (m,2H), 2.75-2.88 (br m,lH), 1.23 (d,d; J=6.6, 6.6 Hz; 3H ) . - — . Example.60 (2R)-2-Benzyl-3-(morpholinocarbamoyl)propionate The product from Example 58 (0.315 g, 0.86 mmol) was dissolved in ethyl acetate (5 mL) and syringed into a flask charged with 10% Pd/C ( '* 0.3 g) . The resulting suspension was exposed to 1 atm of gaseous hydrogen for 2 to 4 h. The catalyst was removed by filtration through a celite pad. The filtrate was concentrated in vacuo to provide the desired compound (0.21 g, 88%) as a cream colored foam which was employed without further purification. Mass spectrum: (M+H) = 278. Example 61 (2R)-2-Benzyl-3-ethoxycarbamoylpropionate The procedure as described in Example 60 was followed employing the product from Example 59 in lieu of that from Example 58. Mass spectrum: (M+H) + = 252. Example 62 Benzyl (2R)-2-benzyl-3-morpholinocarbonylpropionate The product of Example 57 was converted to the title compound using the mixed anhydride method of coupling as described in Example 53. Mass spectrum: (M) + = 367. Example 63 (2R)-2-Benzyl-3-morpholinocarbonylpropionate The product from Example 62 was converted to the title compound following the procedure described in Example 60. Mass spectrum: (M) + = 277. Example 64 (2R)-2-3enzyl-3-(morpholinocarbamoyl)- propionyl-His Amide of 3-Amino- l-cyclohexylmercapto-2-hydroxy-5-methylhexane The resultant compound from Example 52 was treated with ethanolic HCl according to the procedure in Example 51, yielding the corresponding HCl salt which was used as described below without further purifica¬ tion. Coupling of the resultant compound from Example 60 with the above salt was performed, in analogy to the procedure of Example 52, to provide the desired compound. Example 65 (2R)-2-Benzyl-3-(morpholinocarbonyl)- propionyl-His Amide of 3-Amino- l-cyclohexylmercapto-2-hydroxy-5-methylhexane Using the procedure from Example 64 with the resultant compound from Example 63 provided the desired compound. Example 66 2-t-Butyloxycarbonylamino-l-cyclohexylbut-3-ene Using the procedure of Example 48 but replacing Boc-leucinal with Boc-cyclohexylalaninal, gave the desired compound. Mass spectrum: (M+H) = 254. Example 67 3-t-Butyloxycarbonylamino-4-cyclohexyl-l,2-oxobutane Using the procedure of Example 49 with the resultant compound of Example 66 gave the desired compound. Mass spectrum: (M+H) ** • * - 270. Example 68 3-t-Butyloxycarbonylamino-4-cyclohexyl-2-hydroxy-l- isopropylmercaptobutane Using the procedure of Example 50 with the resultant cmpound of Example 67, but replacing cyclohexl mercaptan with isopropyl mercaptan, gave the desired compound. Mass spectrum: (M+H) + = 346. Example 69 3-t-Butyloxycarbonylamino-4-cyclohexyl-2-hydroxy-l- isopropylsulfonylbutane Treating the resultant compound of Example 68 with 2.5 equivalents of 3-chloroperoxy-benzoic acid in dichloromethane, gave the desired compound after work-up as described in Example 49. Mass spectrum: (M+H) τ = 418. Anal. calcd. for C 21 H 33 N0 5 S'0.5 H 2 0: C, 59.10; H, 9.45; N- 3.28. Found: C, 58.90; H, 9.46; N, 3.03. Example 70 Boc-His Amide of 3-Amino-4-cyclohexyl- 2-hydroxy-l-isopropylsulfonylbutane The resultant compound of Example 69 was deprotected in analogy to Example 51 and coupled to Boc-His OH according to Example 52 to provide the desired compound. Mass spectrum: (M) = 514. Example 71 Boc-Leu Amide of 3-Amino-4-cyclohexyl-2-hydroxy-l- isopropylsulfonylbutane The resultant compund of Example 69 was depro¬ tected in analogy to Example 51 and coupled to BocLeuOH in analogy to Example 53 to provide the desired compound. Mass spectrum: (M+H) = 491. Example 72 (2R)-2-Benzyl-3-(morpholinocarbonyl)- propionyl-His Amide of3-Amino-4-cyclohexyl- 2-hydroxy-l-isopropylsulfonylbutane Using the procedure of Example 65 with the resultant compound of Example 70 provided the desired compound. Mass spectrum: (M+H) = 674. Example 73 (2R)-2-Benzyl-3-(morpholinocarbonyl)- propionyl-Leu Amide σf3-Amino-4-cyclohexyl- 2-hydroxy-l-isopropylsulfonylbutane Using the procedure of Example 65 with the resultant compound of Example 71 provided the desired compound. Example 74 (2S)-2-Benzyl-3-(ethoxycarbamoyl)-propionyl-His Amide of 3-Amino-4-cyclohexyl-2-hydroxy-l-isopropylsulfonylbutane Using the procedure of Example 64 with the resultant compounds of Examples 61 and 70 provided the desired compound. Mass spectrum: (M+H) = 648. Anal, calcd. for C 32 H 4g 5 0 7 S" 1.5H 2 0: C, 56.95; H, 7.77; N, * 10.38. Found: C, 56.99; H, 7.47; N, 10.27. Example 75 (2S)-2-Benzyl-3-(ethoxycarbamoyl)-propionyl-Leu Amide of 3-Amino-4-cyclohexyl-2-hydroxy-l-isopropylsulfonylbut ne Using the procedure of Example 74 with the resultant compound of Example 71 in lieu of the resultant compound from Example 70, provided the desired compound. Example 76 (3S,4S)-3-hydroxy-4-t-butyloxycarbonyl- amino-5-cyclohexylpentanenitrile To a solution of lithium diisopropylamide (4.40 mmol) in dry tetrahydrofuran (4 L) at -78°C was added acetonitrile (0.25 mL, 4.4 mmol). To this enolate suspension was added 2(S)-t-butyloxycarbonylamino- 3-cyclohexylpropanal (0.76 g, 2.98 mmol) in tetrahydro¬ furan (5 mL) pre-cooled to -78°C. After stirring for 15 min, the mixture was quenched with 2M HCl (2.3 mL) , warmed to -10°C, acidified with 2M HCl (5.0 mL) , and extracted with ether which was dried over MgS0 4 and evaporated. Flash chromatography on silica gel with ethyl acetate/hexane mixtures afforded 0.360 g (41%) of the desired compound as an oil. Anal. Calcd for C 16 H 28 N 2°3°" 4 H 2 0: C, 63.30; H, 9.56; N, 9.23. Found: C, 63.51; H, 9.66; N, 8.81. Example 77 (3S,4S)-l-Amino-3-hydroxy-4-t-butyloxycarbonylamino- 5-cyclohexylpentane (3S, S)-3-Hydroxy-4-t-butyloxycarbonylamino- 5-cyclohexylpentane nitrile (0.2300 g, 0.766 mmol) and Raney nickel (0.230 g) were hydrogenated at 3 atm in methanol (20 mL) and ammonia (15 mL) . The mixture was filtered, evaporated, dissolved in ethyl acetate and extracted with 0.5 M H.PO.. The aqueous phase was made basic with solid K«CO, and extracted with 25% isopropanol in chloroform which was dried over a 2 S0 4 and evaporated to afford 0.1520 g (65%) of the desired product as an oil. Exact mass calculated for C 16 H 32 N 2 0 3 : 300.2411. Found: 300.2439. Examole 78 (3S,4S)-l-(3-Methylbutylcarbonylamino)-3-hydroxy-4-t- butyloxycarbonylamino-5-cyclohexylpentane To (3S,4S)-l-amino-3-hydroxy-4-t-butyloxy- carbonylamino-5-cyclohexylpentane (30.8 mg, 0.102 mmol) in dry methylene chloride (3 mL) at 0°C was added 4-methylpentanoyl chloride (17.0 uL, 0.123 mmol) and triethylamine (20.0 uL, 0.143 mmol). The mixture was stirred at 0°C for 1 h, evaporated, taken up in methanol (3 L) and treated with 1 M NaOH (1 mL) . After stirring for 1 h, the mixture diluted with ether, washed sequentially with 0.5 M H 3 P0 4 , saturated NaHC0 3 solution, and brine, and then dried over N 2 S0 4 and evaporated o afford 41.0 mg (100%) of the desired product as an oil. Analysis Calculated for C 1 6 H 28 N 2°3 0.25 H 2 0: C, 65.55; H, 10.63; N, 6.95. Found: C, 65.52; H, 11.02; N, 6.77. Example 79 Boc-Phe-His Amide of (3S,4S)-l-(3-Methylbutyl- carbonylamino)-3-hydroxy-4-amino-5-cyclohexylpentane The resultant compound from Example 78 (36.9 mg, 0.0926 mmol) was stirred for 1 h in 4 M HCl in dioxane. The solvent was removed and dimethylformamide (0.5 mL) and N-methylmorpholine (23 uL, 0.21 mmol) were added. To Boc-Phe-His-OH (38.5 mg, 0.0957 mmol) and 1-hydroxybenzotriazole (39.5 mg, 0.292 mmol) in dimethylformamide (0.3 mL) at -23°C was added 1-ethyl- 3-dimethylaminσpropylcarbodiimide hydrochloride (18.9 mg, 0.0986 mmol). After 1 h the amine solution was added and after an additional 2 h, the mixture was warmed to room temperature and stirred for 18 h. The mixture was poured into saturated NaHC0 3 solution and extracted into ethyl acetate which was washed with water and brine, then dried over Na 2 S0 4 and evaporated. Chromatography of the residue on silica gel with 3% CH 3 0H/CHC1 3 afforded 43.3 mg (69%) of a white solid, m.p. 168-172°C. Example 80 Boc-His Amide of (3S,4S)-l-(3-Methylbutylcarbonylamino)- 3-hydroxy-4-amino-5-cyclohexylpen ane Using the procedure of Example 79 with the resultant compound of Example 78 and Boc-His-OH rather than Boc-Phe-His-OH, gave the desired compound. Example 81 (3S,4S)-l-(2-Propylsulfonylamino)-3-hydroxy-4-t- butyloxycarbonylamino-5-cyclohexylpentane Using the procedure of Example 78 employing the resultant compound from Example 77 and isopropylsulfonyl chloride instead of 4-methylpentanoyl chloride afforded the desired compound. Example 82 Boc-Phe-His Amide of (3S,4S)-l-(2-Propylsulfonylamino)- 3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 employing the resultant compound from Example 81 gave the desired compound, m.p. 174-177°C. Example 83 Boc-Phe-dl-3-pyrazolylalanine Methyl Ester To dl-3-pyrazolylalanine methyl ester dihydro- chloride (dl connotes 50/50 mixture of dextrorotatory/ levorotatory) (2.05 g, 8.5 mmol) in dimethylformamide (10 mL) at -10°C was added Boc-Phe N-hydroxysuccinimide ester (2.50 g, 6.90 mmol) and N-methylmorpholine (2.8 mL, 25 mmol). The mixture was stirred at -10°C for 1 h and then at 25°C for 12 h. The mixture was partitioned between ethyl acetate and saturated NaHC0 3 solution, and extracted with ethyl acetate which was washed with water, dried over Na 2 S0 4 and evaporated to afford 2.75 g (95%) of the desired product. Analysis calculated for C 21 H 2 8 N 4 °_ 5 0.25 H 2 0: C, 59.92; H, 6.82; N. 13.31. Found: C, 59.82; H, 6.75; N, 13.13. Example 84 Boc-Phe-dl-3-pyrazolylalanine Boc-Phe-dl-3-pyrazolylalanine methyl ester (0.210 g, 0.505 mmol) in dioxane (1.5 mL) and water (1.0 mL) was treated with lithium hydroxide monohydrate (0.0272 g, 0.648 mmol), stirred at 25°C for 30 min and quenched with 0.32 mL 2 M HCl. The mixture was poured into chloroform, washed with water, dried over Na 2 S0 4 and evaporated to afford 0.184 g (91%) of the desired compound. Analysis calculated for C 2 0 H 2 6 N 4 ° 5 0.25 H 2 0: C, 59.03; H, 6.56; N, 13.77. Found: C, 58.66; H, 6.70; N, 13.65. Example 85 Boc-Phe-dl-3-pyrazolylalanine Amide of (3S,4S)-1-(3-Methylbutylcarbonylamino)- 3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 with the resultant compound from Example 78 and using the resultant compound from Example 84 rather than Boc-Phe-His-OH afforded the desired compound. Anal. Calcd for C 3 -.H 58 6 0g 0.75 H 2 0: C, 63.81; H, 8.61; N, 12.07. Found: C, 63.95; H, 8.70; N, 11.79. Example 86 Ethyl (3R,4S)-3-hydroxy-4-t-butyloxycarbonylamino- 2,2-difluoro-5-cyclohexylpentanoate Boc-cyclohexylalanal (6.60 g, 25.8 mmol) in dry tetrahydrofuran (THF, 100 mL) was treated with ethyl bromodifluoroacetate (10.5 g, 51.7 mmol) and zinc dust (4.25 g, 65.0 mmol). The mixture was subjected to ultrasonic mixing (15-25°C) for 2 h, then poured into saturated aqueous NaHC0 3 solution which was extracted with ethyl acetate. The organic phases'were dried over Na 2 S0 4 , evaporated, and the residue was chromato¬ graphed on silica gel with ethyl acetate/hexane mixtures to afford 3.27 g (33%) of the desired compound and 1.45 g (15%) of the 3S isomer. 3R isomer: m.p. 106-109°C; 3S isomer: m.p. 71-73°C. Example 87 (3R,4S)-l,3-dihydroxy-2,2-difluoro- 4-t-butyloxycarbonylamino-5-cyclohexylpentane To the resultant compound from Example 86 (525.0 mg, 1.38 mmol) in methanol (6 mL) was added NaBH 4 (106 mg, 2.8 mmol). The mixture was stirred for 1 h, poured into saturated aqueous NaHC0 3 solution, and extracted with ethyl acetate which was dried over a 2 S0 4 and evaporated to afford 467 mg (100%) of the desired product. DCI-MS: (M+H) + = 338. Example 88 (3R,4S)-4-Cyclohexylmethy1- 5-(2-hydroxy-l,1-difluoroethyl)-2-oxazolidinone The resultant compound from Example 87 (596 mg, 1.77 mmol) in dry dimethylformamide (DMF, 15 mL) was added to NaH (260 mg, 6.5 mmol, 60% in oil, hexane washed) in DMF (5 mL) at 0°C. The mi.rture was stirred at room temperature for 16 h and the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous NaHCO., solution and the organic phase was dried over Na 2 S0 4 and evaporated to afford 472 mg (100%) of product as an oil. - - Anal. Calcd for C 12 H 19 F 2 N0 3° ' 25 H 2 0: C, 53.82; H, 7.34; N, 5.23. Found: C, 54.01; H, 7.05; N, 5.32. Example 89 (3R,4S)-4-Cyclohexylmethyl- 5-(2-mesyloxy-l,1-difluoroethyl)-2-oxazolidinone To the resultant compound from Example 88 (460 mg, 1.75 mmol) in CH 2 C1 2 (5 mL) at 0°C was added triethylamine (0.36 L, 2.6 mmol) and methane- sulfonyl chloride (135 uL, 1.74 mmol). After stirring at 0°C for 20 min, the mixture was diluted with ethyl acetate, washed sequentially with 0.5 M H 3 P0 4 , saturated aqueous NaHC0 3 solution, and brine, then dried over a 2 S0 4 and evaporated to afford 558 mg (94%) product as an oil. Mass spectrum: FAB, (M+H) + = 342. Example 90 (3R,4S)-4-Cyclohexylmethyl- 5-(2-azido-l,1-difluoroethyl)-2-oxazolidinone To the resultant compound from Example 89 (179.9 mg, 0.527 mmol) in dimethylformamide (DMF, 3 mL) was added NaN 3 (111.0 mg, 1.71 mmol) and the mixture was heated 100-110°C for 16 h. The mixture was poured into ethyl acetate which was washed with water and brine, dried over Na 2 S0 4 and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane mixtures afforded 116.9 mg (77%) product as an oil. Mass specrum: El, (M+H) + = 289. Example 91 (3R,4S)-4-Cyclohexyl ethyl-5-(2-isopropylmercapto-l, 1- difluoroethyl)-2-oxazolidinone To NaH (85.0 mg, 2.22 mmol, 60% in oil, hexane washed) in DMF (4 mL) at 0°C was added isopropyl- ercaD an (0.40 L, 4.3 mmol). After 15 min the resultant compound from Example 89 (373.4 mg, 1.09 mmol) in DMF (4 mL) was added and the mixture was heated 50-60°C for 16 h. The mixture was poured into ethyl acetate which was washed with water and brine, dried over 2 S0 4 and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane mixtures afforded 258.0 mg (73%) product as a solid, m.p. 75-76°C. Anal. Calcd for C 15 H 25 F 2 N0 2 S: C, 56.05; H, 7.84; N, 4.36. Found: C, 56.09; H, 8.02; N, 4.14. Example 92 (3R,4S)-4-Cyclohexylmethyl- 5-(2-isopropyloxy-l,1-difluoroethyl)-2-oxazolidinone Using the procedure of Example 91 and isopropanol instead of isopropyl mercaptan afforded the desired product. Example 93 (3R,4S)-3-Hydroxy-4-amino-2,2-difluoro- 1-azido-5-cyclohexyIpentane To the resultant compound from Example 90 (113.9 mg, 0.395 mmol) in dioxane (4.5 mL) and water (3 L) was added Ba(OH) 2 8 H 2 0 (0.25 g, 0.79 mmol) and the mixture was heated at reflux for 13 h. The mixture was filtered, and the filtrate was concentrated, partitioned between water and ether, and extracted with ether. The organic extract was dried over Na 2 S0 4 and evaporated to afford 108 mg (100%) product as an oil. Mass spectrum: FAB, (M+H) + = 263. Example 94 (3R,4S)-3-Hydroxy-4-amino-2,2-difluoro-1-isopropyloxy- 5-cyclohexylpentane Using the procedure of Example 93 with the resultant compound from Example 92 afforded the desired compound. Example 95 Boc-Phe-Leu Amide of (3R,4S)-3-hydroxy-4-amino- 2,2-difluoro-l-azido-5-cyclohexylpentane To Boc-Phe-Leu-OH (169.8 mg, 0.449 mmol) in THF (2 mL) at -10°C was added N-methylmorpholine (48 uL, 0.44 mmol) followed by isobutyl chloroformate (57 uL, 0.44 mmol). After 3 min, the resultant compound from Example 93 (105.0 mg, 0.40 mmol) in THF (4 mL) was added and the reaction was stirred at -10°C 15 min then at room temperature for 2 h. The mixture was diluted with ethyl acetate, washed sequentially with 0.5 M H 3 P0 4 , saturated aqueous NaHC0 3 solution, and brine, then dried over Na 2 S0 4 and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane mixtures afforded 184.0 mg (74%) product as a glass. NMR (300 MHz, CDC1 3 , ppm): 0.9 (d,6H), 1.4 (S,9H), 3.15-3.00 (m,2H), 3.80-3.60 (m,3H), 4.05-3.95 (m,lH), 4.4-4.2 (m,2H), 4.85 (d,lH), 5.10 (d,lH), 6.15 (d,lH). Example 96 Boc-Phe-Leu Amide of (3R,4S)-3-hydroxy- 4-amino-2,2-difluoro-l-isopropyloxy-5-cyclohexylpentane Using the procedure of Example 95 with the resultant compound from Example 94 afforded the desired product. Example 97 Boc-Phe-Leu Amide of (3R,4S)-3-hydroxy-4-amino- 2,2-difluoro-l-isopropylmercapto-5-cyclohexylpentane Using the procedure of Example 95 and the resultant compound from Example 91 which had been hydrolyzed to the free amine according to the procedure in Example 93 afforded the desired product. Anal. Calcd for C 34 H-.-.F 2 N 3 0 5 S: C, 62.26; H, 8.45; N, 6.41. Found: C, 62.32; H, 8.78; N, 6.19. Example 98 Boc-Phe-Leu Amide (4-amino) of (3R,4S)- 3-hydroxy-l,4-diamino-2,2-difluoro-5-cyclohexylpentane The resultant compound from Example 95 (72.0 mg) and 10% palladium on carbon (42 mg) in methanol (3 mL) and acetic acid (1 mL) were stirred under a hydrogen atmosphere for 8 h. The mixture was filtered, concentrated, and partitioned between ethyl acetate and 1 M aqueous 2 C0 3 solution. The organic extracts were dried over N 2 SO Λ and evaporated to afford 63.2 mg (92%) of the desired product as a solid. Mass spectrum: El, M + = 596. Example 99 Boc-Phe-Leu Amide of (3R,4S)- 3-hydroxy-4-amino-2,2-difluoro- l-isopentylcarbonylamino-5-cyclohexylpentane To the resultant compound from Example 98 (586 mg, 0.0982 mmol) in CH 2 C1 2 (2 mL) at 0°C was added N-methylmorpholine (16 uL, 1.5 mmol) and iso- caproyl chloride (15 uL, 0.11 mmol). After stirring at room temperature for 1 h the mixture was diluted with ethyl acetate, washed sequentially with 0.5 M H 3 P0 4 , saturated aqueous NaHC0 3 solution and brine, dried over Na 2 S0 4 and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane mixtures afforded 39.6 mg (58%) product as a solid. Anal. Calcd for C 3_7H6 r 0-F o 2 4.0 c 6: C, 63.95; H, 8.70; N, 8.06. Found: C, 64.07; H, 9.07; N, 7.73. Example 100 Boc-Phe-Leu Amide of (3R,4S)-3-hydroxy-4-amino- 2,2-difluoro-1-isopropylsulfonyl-5-cyclohexylpentane To the resultant compound from Example 97 (50.0 mg, 0.0762 mmol) in CH 2 C1 2 (2 mL) was added m-chloroperbenzoic acid (42.0 mg, 0.20 mmol, 80% pure). After 1 h the mixture was diluted with ethyl acetate, washed sequentially with cold 10% aqueous Na 2 S0 3 solution, saturated aqueous NaHC0 3 solution and brine, then dried over Na 2 S0 4 and evaporated. Chromatog¬ raphy on silica gel with ethyl acetate/ hexane mixtures provided 42.4 mg (81%) product as a solid. Anal, Calcd for C,.H__F n N_0_S: C, 59.37; H, 8.06; N, 6.11. Found: C, 59.05; H, 8.33; H, 5.76. Example 101 Boc-Phe-Leu Amide of (4S)-3-oxo-4-amino- 2,2-difluoro-l-azido-5-cyclohexylpentane To oxalyl chloride (19 uL, 0.22 mmol) in CH 2 C1 2 (1 mL) at -60°C was added dimethylsulfoxide (24 uL, 0.34 mmol) in CH 2 C1 2 (1 mL) . After 15 min the resultant compound from Example 95 (44.0 mg, 0.0707 mmol) in CH 2 C1 2 (3 mL) was added. The reaction was stirred for 20 min and triethylamine (75 uL, 0.54 mmol) was added. The mixture was stirred for 20 min, poured quickly into cold 20% saturated aqueous NaHSO. solution and diluted with ethyl acetate (4 mL) and hexane (12 mL) . The organic phase was washed with water then brine, dried over Na 2 S0 4 and evaporated. Chromatography of the residue on silica gel with ethyl acetate/hexane mixtures provided 37.3 mg (85%) product as a solid. Mass spectrum: El, M = 620. Example 102 Boc-Phe-Leu Amide of (4S)-3-oxo-4-amino-2,2-difluoro- l-isopropylsulfonyl-5-cyclohexylpentane Using the procedure of Example 101 with the resultant compound from Example 100 afforded the desired product as a solid. Anal. Calcd for C 34 H 53 F 2 N 3 O 7 S'0.5 H 2 0: C, 58.77; H, 7.83; N, 6.05. Found: C, 58.85; H, 7.87; N, 5.90. Example 103 Boc-Phe-Leu Amide of (4S)-3-oxo-4-amino- 2,2-difluoro-l-isopropyloxy-5-cyclohexylpentane Using the procedure of Example 101 with the resultant compound from Example 96 provided the desired product. Example 104 Boc-Phe-Leu Amide of (4S)-3-oxo-4-amino-2,2-difluoro- l-isopropylmercapto-5-cyclohexylpentane Using the procedure of Example 101 with the resultant compound from Example 97 provided the desired product as a solid. Anal. Calcd for C 34 H 53 F 2 3 0 5 S" 0.5 H 2 0: C, 61.61; H, 8.21; N, 6.34. Found: C 61.68; H, 8.25; N, 6.22. Example 105 Boc-Phe-Leu Amide of (4S)-3-oxo-4-amino-2,2-difluoro-1- isopentylcarbonylamino-5-cyclohexylpentane Using the procedure of Example 101 with the resultant compound from Example 99 provided the desired product as a solid. Anal. Calcd for C 37 H_ Q F 2 4 0 6 : C, 64.14; H, 8.44; N, 8.09. Found: C 63.84; H, 8.43; N, 7.89. Example 106 (2S,3S)-l-Azido-3-t-butyloxycarbonylamino- 2-hydroxy-5-methylhexane A stirred solution of the resultant compound of Example 49 (1.0 mmol) in methanol (10 mL) was refluxed with sodium azide (2.4 mmol) and ammonium chloride (1.8 mmol) for 2 h. The solvent was evaporated, and the residue was extracted with several portions of hot chloroform. The extract was filtered and evaporated to a residue which was chromatographed on Si0 2 eluting with hexane/ether mixtures to give the desired compound in 76% yield, m.p. = 50-52°C. Example 107 (2S,3S)-l-Amino-3-t-butyloxycarbonylamino-2-hydroxy- 5-methylhexane Hydrochloride The resultant compound of Example 106 (400 mg) dissolved in methanol containing added CHC1 3 was hydrogenated over 10% Pd/C (40 mg) with 3 atmospheres hydrogen. Filtration and evaporation gave the desired compound (305 mg) . Example 108 (2S,3S)-3-t-Butyloxycarbonylamino-2-hydroxy- l-(isovalerylamino)-5-methylhexane To a solution of the resultant compound of Example 107 (1.0 mmol) and triethyl amine (2.0 mmol) in chloroform (10 mL) cooled to 0°C was added isovaleryl chloride (1.0 mmol) in CHC1 3 (2 mL) . After 3 h, the solution was washed sequentially with 10% citric acid, saturated NaHC0 3 , and brine. Drying and evaporating provided the desired compound. Example 109 (2S,3S)-l-Azido-2-hydroxy-3-t-butyloxycarbonylamino- 4-cyclohexylbutane The resultant compound from Example 67 was treated according to the procedure of Example 106 to give the desired compound. t Anal. Calcd for C 15 H 2 gN 4 0 3 : C, 57.67; H, 9.03; N, 17.93. Found: C, 57.54; H, 9.14; N, 17.57. Example 110 Boc-Phe-His Amide of (2S-3S)- l-(Isovalerylamino)-2-hydroxy-3-amino-5-methylhexane Using the procedure of Example 79 with the resultant compound from Example 108 gave the desired compound. Anal. Calcd for C, 32H c 5 n 0N c 606:0.5 H 4-0: C, 61.62; H, 8.24; H, 13.47. Found: C, 61.68; H, 8.31; N, 13,34. Example 111 Boc-Phe-His Amide of (2S,3S)-l-Azido- 2-hydroxy-3-amino-4-cyclohexylbutane Using the procedure of Example 79 with the resultant compound from Example 109 gave the desired compound. Anal. Calcd for C 3, n 0H4.4.N8.O5IH-2O; C, 58.62; H, 7.54; N, 18.22. Found: C, 58.71; H, 7.45; N, 18.22. Example 112 4(S)-t-Butyloxycarbonylamino- 5-cyclohexyl-3(R,S)-hydroxyl-l-pentene. To a stirred -78°C solutio . of Boc-cyclohexyl- alanine methyl ester (10.2 g, 35.8 mmol) in dry toluene (60 L) was added diisobutylaluminum hydride (34 mL of a 1.5 M solution in toluene). After 30 min, vinyl magnesium bromide (108 mL of 1 M solution in tetra¬ hydrofuran (THF)) was added. After stirring for 15 h at 0°C, the mixture was carefully quenched with methanol, treated with Rochelle salts (22 mL of saturated aqueous solution in 140 mL H 2 0 * ) ' anc ^ filtered. After extracting the solids 5 times with ethyl acetate, the extracts and filtrate were combined and the organic phase was washed with brine, dried, filtered and evaporated to an oil (10.2 g) . Chromatography on silica gel eluting with hexane/ethyl acetate mixtures provided 6.1 g (60%) of the desired product. Anal. Calcd for C 16 H 2g N0 3 H 2 0: C, 66.8; H, 10.3; H, 4.9. Found: C, 66.9; H, 10.2; N, 4.7. Example 113 4(S)-Cyclohexylmethyl-5(R,S)-viny1-2-oxazo1idinone The resultant product of Example 112 (2.80 g, 9.88 mmol) in dry dimethylformamide (DMF) (50 mL) was added to a stirred suspension of NaH (593 mg of a 60% dispersion in oil, 14.8 mmol, hexane washed) in dry DMF (50 mL) . After 3 h, the mixture was quenched (750 mL water +.. 100 mL brine) and extracted with ether (5 x 100 mL) . The combined organic phase was washed with brine (3 x 50 mL) , dried (MgS0 4 ), filtered and evaporated to an oil (2.23 g) . The NMR spectrum of the crude product revealed an 82:18 mixture of 5S:5R diastereomers. Silica gel chromatography gave 80% recovery of pure diastereomers. 5S: Anal. Calcd for C 12 H ιg N0 2 : C, 68.9; H, 9.1; N, 6.7. Found: C, 68.4; H, 9.2; N, 6.5. Mass spectrum: (M+l) + = 210. - 5R: Mass spectrum: (M+l) + = 210. Example 114 (3S,4S)-3-Hydroxy-4-amino-5-cyclohexyl-l-pentene To the resultant 5S-diasteriomer from Example 113 (2.06 g, 9.84 mmol) in dioxane (180 mL) and water (120 mL) was added barium hydroxide octahydrate (6.24 g, 19.8 mmol). The mixture was refluxed for 18 h, cooled, filtered, concentrated, taken up in water and extracted with ethyl acetate which was dried over 2 S0 4 and evaporated to afford 1.64 g (91%) of the desired product, mp: 59-61°C. Anal. Calcd for C n H 21 N0: C, 72.08; H, 11.55; N, 7.64. Found: C, 71.67; H, 11.68; N, 7.36. Example 115 (3S,4S)-3-Hydroxy-4-tert-butoxycarbonylamino- 5-cyclohexyl-l-pentene. To the resultant compound from Example 114 (1.62 g, 8.84 mmol) in methylene chloride (20 mL) was added di-tert-butyldicarbonate (1.93 g, 8.84 mmol). The mixture was stirred for 14 h, diluted with ethyl acetate, washed sequentially with 0.5 M H 3 P0 4 , saturated NaHC0 3 solution and brine, then dried over 2 S0 4 and evaporated to afford 2.51 g (100%) of the desired compound. Example 116 (3S,4S)-1,3-Dihydroxy-4-t-butyloxycarbonylamino- 5-cyclohexylpentane The resultant compound from Example 115 (327.6 mg, 1.16 mmol) in tetrahydrofur n (THF, 3 mL) of 0°C was treated with 9-borabicyclo(3.3. Dnonane (4.6 mL, 2.3 mmol in THF). After 3 h at room temperature water (0.1 mL) then NaOH (280 mg, 7.0 mmol) in water (1 mL) then 30% H 2°2 (°* 70 mL ' 6.9 mmol) were added and the mixture was heated at 50°C for 90 min. The mixture was concentrated, dissolved in ethyl acetate, washed with brine, dried over 2 S0 4 , evaporated and chromato¬ graphed on silica gel with 2% methanol in chloroform to give 351.1 mg (100%) of the desired compound as an oil. DCI-MS: (M+H) = 302. Example 117 (3S,4S)-l-Mesyloxy-3-hydroxy- 4-t-butyloxycarbonylamino-5-cyclohexylpentane The resultant compound from Example 116 was reacted according to the procedure in Example 89 to give the desired compound. EI-MS: M + = 379. Example 118 ' (3S,4S)-l-Azido-3-hydroxy-4-t-butyloxycarbonylamino- 5-cyclohexylpent ne The resultant compound from Example 117 was reacted according to the procedure in Example 90 to give the desired compound. DCI-MS: (M+H) = 327. Example 119 Boc-Phe-His Amide of (3S,4S)-l-Azido- 3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 with the resultant compound from Example 118 gave the desired compound. Anal. Calcd for C 31 H 46 N 8°5 0,5 H 2 0: C, 60.08; H, 7.64; N, 18.08. Found: C, 60.35; H, 7.48; N, 17.75. Example 120 l-Benzyloxycarbonylamino-2,3-propanediol l-Amino-2,3-propanediol (15.2 g, 167 mmol) and NaOH (8.1 g, 204 mmol) in water (70 mL) at -10°C was treated dropwise with benzyl chloroformate (28.5 L, 200 mmol) in ether (30 mL) over 20 min. The reaction was stirred at 0°C for 30 min then at room temperature for 2 h. The mixture was acidified with 2 M HCl and extracted with ethyl acetate which was washed with 0.5 M H 3 P0 4 and brine, then dried over Na 2 S0 4 and evaporated. Recrystallization of the residue from benzene afforded 16.59 g (44%) of the desired product as a white powder. NMR (300 MHz, CD 3 0D, ppm): 3.12 (dd,lH), 3.28 (dd,lH), 3.50 (m,2H), 3.68 (m,lH), 5.08 (s,2H), 7.35 (m,5H). Example 121 l-Methylamino-2,3-propanediol Lithium aluminum hydride (7.20 g, 189 mmol) in tetrahdyrofuran (THF, 300 mL) was heated to reflux and the resultant compound from Example 120 (17.0 g, 75.5 mmol) in THF (150 mL) was added dropwise over 10 min. The mixture was relfuxed for 2 h, cooled, quenched sequentially with water (10 mL) , 3 M NaOH (40 mL) and water (20 mL) , then filtered and concentrated. The residue was dissolved in water which was washed with ether and evaporated. Bulb to bulb distillation of the residue afforded 2.0 g (25%) of the desired compound as an oil. NMR (300 MHz, CDC1 3 , ppm): 2.45 (S,3H), 2.68 (dd,lH), 2.77 (dd.lH), 3.61 (dd.lH), 3.72 (dd,lH), 3.78 (M,1H) . Example 122 (N-Methy1-2,3-dihydroxypropylamino)carbonyl-(O-methyl) tyrosine methyl ester To the resultant compound from Example 136 (1.53 g, 6.5 mmol) in dioxane (5 mL) at 0°C was added the resultant compound from Example 121 (0.684 g, 6.5 mmol). The reaction was stirred at 0°C for 1 h then at room temperature for 1 h, evaporated and chromatographed on silica gel with 5% methanol in chloroform to afford 1.855 g (84%) of the desired product as an oil. NMR (300 MHz, CDC1 3 , ppm), 2.88, 2.89 (S,3H total), 3.05 (m,2H)., 3.26-3.60 (m,5H), 3.73 (S,3H), 3.80 (S,3H), 4.70 (m,lH), 5.07 (broad t,lH), 6.83 (dd,lH), 7.02 (dd,lH). Example 123 (N-Methyl-2,3-dihydroxypropylamino)carbonyl- (O-methy1)tyrosine The resultant compound from Example 122 (114 mg, 0.355 mmol) in dioxane (4 mL) and water (2 mL) at 0°C was treated with LiOH monohydrate (42.0 mg, 1 mmol). After 90 min 2 M HCl (0.6 mL, 1.2 mmol) was added and the mixture was evaporated to a foam which was uussee(d without further purification; DCI-MS: (M+H) 327 Example 124 (2R)-3-(N-Methyl-2,3-dihydroxypropylamino)- carbonyl-2-benzylpropionic Acid Benzyl Ester Prepared according to the procedure for Example 95 from the resultant compounds of Example 121 and Example 57. NMR (300 MHz, CDC1 3 , ppm), 3.00 (s,3H), 5.10 (m,2H), 7.10-7.40 (m,10H); EI-MS: M + = 385. Example 125 (2R)-3-(N-Methyl-2,3-dihydroxypropylamino)carbonyl- 2-benzylpropionic Acid The resultant compound from Example 124 (200 mg, 0.523 mmol) and 10% Pd on carbon (200 mg) in methanol (10 mL) were stirred under a hydrogen atmosphere for 3 h. The reaction was filtered and evaporated to afford 148 mg (97%) of the desired product as an oil. Anal. Calcd for c i5 H 2i N0 5 0, 25 H 2 0: C , 60 . 09 ; H , 7 . 23 ; N, 4 . 67 . Found: C, 59.76; H, 7.10; N, 4.45. Example 126 Dimethylaminocarbonyl-(Q-methyl)tyrosine Methyl Ester Prepared from dimethyl amine and the resultant compound from Example 136 according to the procedure for Example 122. Example 127 Dimethylaminocarbonyl-(O-methyl)-tyrosine Prepared according to the procedure of Example 123 from the resultant compound of Example 126 with the modification that the product was isolated by pouring the reaction mixture into 2 M HCl and extracting with ethyl acetate which was dried over Na 2 S0 4 and evaporated. EI-MS: M + = 266 Anal. Calcd for c i3 H i8 N 2°4 : C ' 58.64; H, 6.81; N, 10.52. Found: C, 58.44; H, 6.87; N, 9.95. Example 128 3,3-D.imethylqlutaric Acid Mono t-butyl Ester 3,3-Dimethylglutaric anhydride (455 mg, 3.2 mmol) in tetrahydrofuran (THF, 5 mL) was treated with sublimed potassium t-butoxide (395 mg, 3.5 mmol). After 30 min the solution was concentrated, poured into saturated NaHC0 3 solution and washed with ether. The aqueous phase was acidified to pH 4 with 0.5 M H 3 P0 4 and extracted with chloroform which was dried over a 2 S0 4 and evaporated to afford 179 mg (26%) of the desired product as an oil. NMR (300 MHz, CDC1 3 , ppm), 1.13 (s,6H), 1.47 (s,9H), 2.33 (s,2H), 2.45 (s,2H). Example 129 (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoyl- phenylalanine benzyl Ester Prepared according to the procedure from Example 95 from the resultant compound from Example 128 and phenylalanine benzyl ester p-toluenesulfonic acid salt. NMR (300 MHz, CDC1 3 , ppm), 0.96 (s, 3H) , 1.00 (s, 3H), 1.44 (s, 9H), 1.90 (d, 1H) , 2.16 (d, 1H) , 2.25 (d, 1H), 2.29 (d, 1H) , 3.03 (dd, 1H) , 3.17 (dd, 1H), 4.92 (m, 1H), 5.12 (d,lH), 5.16 (d,lH), 7.10-7.40 (m,10H) . Example 130 (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylpenylalanine Using the procedure of Example 125 with the resultant compound of Example 129 gave the desired product as an oil. NMR (300 MHz, CDC1 3 , / ppm) , 0 . , 93 (S,3H), 0.99 (s,3H), 1.45 (s,9H), 1 . 77 (d, lH) , 2 . , 10 (d,lH), 2.19 (d,lH), 2.25 (d,lH), 3 . 02 ι ( dd. lH ) , 3 . , 33 (dd,lH), 4.72 (m,lH), 7.25 (m,5H). Example 131 Dimethylaminocarbonyl (O-methyl)Tyr-His Amide of (3S,4S)-l-(3-Methylbutylcarbonylamino)- 3-hydroxy-4-amino-5-cyclohexylpen ane Using the procedure of Example 79 with the resultant compounds from Example 127 and Example 80 gave the desired compound. Example 132 (N-Methyl-2,3-dihydroxypropylamino)carbonyl- (O-methyl)Tyr-His Amide of (3S,4S)-l-(3-Methylbutyl- carbonylamino)-3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 with the resultant compounds from Example 122 and Example 80 gave the desired compound. Example 133 (2R)-3-(N-Methyl-2,3-dihydroxypropylamino)carbonyl- 2-benzylp " ropionyl-His Amide of (3S,4S)-l-(3-Methyl-butylcarbonylamino)- 3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 with the resultant compounds from Example 125 and Example 80 gave the desired compound. Example 134 (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoyl- Phe-His Amide of (3S, S)-l-(3-Methylbutyl- carbonylamino)-3-hydroxy-4-amino-5-cyclohexylpentane Using the procedure of Example 79 with the resultant compounds from Example 130 and Example 80 gave the desired compound. Example 135 (4-Hydroxycarbonyl-3,3-dimethyl)butanoyl- Phe-His Amide of (3-Methylbutylcarbonylamino)- 3-hydroxy-4-amino-5-cyclohexylpentane HCl Salt The resultant compound from Example 134 was stirred in 4 M HCl/methanol for 1 h and then evaporated to provide the desired compound. Example 136 α -Isocyanato-L-(Q-methyl)tyrosine A suspension of (O-methyl)tyrosine methyl ester hydrochloride (6 g) in toluene (125 mL) was heated at 100°C while phosgene was bubbled into the reaction mixture. After 2 h the mixture became homogeneous and the phosgene was continued for an additional 15 min. The mixture was cooled and evaporated with several benzene chasers to provide the desired product. Example 137 2-t-Butyloxycarbσnylamino-l-cyclohexyl- 3-hydroxy-6-methylheptane To a stirred -78°C solution of L-Boc-cyclo- hexylalaninal (1.0 g, 3.9 mmol) in anhydrous tetrahydro¬ furan (THF, 25 mL) was added isoamyl magnesium bromide (24.4 mL of 0.8 M solution in THF) dropwise over the course of 5 min. The mixture was warmed to 0°C for 2 h and then quenched with NH 4 C1 (1.34 g, 25 mmol) in H 2 0 (25 mL) . The THF was evaporated and the aqueous phase was extracted with ether (3 x 40 mL) . The combined organic phase was washed (brine) , dried (Na 2 S0 4 ), evaporated, and chromatographed on silica gel eluting with ethyl acetate/hexane (15/85). Combination of selected fractions provided the less polar "S"-hydroxy diastereoamer (375 mg, 29%). Mass spectrum: M = 327. Example 138 Boc-Phe-His Amide of 2-Amino-l-cyclohexyl- 3-hydroxy-6-methylheptane. The resultant compound of Example 137 (320 mg, 0.977 mmol) was dissolved in 25 mL of anhydrous 1 M HCl in methanol. After 12 h, evaporation of the solvent provided the corresponding deprotected amine hydro¬ chloride (241 mg, 93%) which was used in the below coupling without further purification. To a stirred -23°C solution of Boc-Phe-His-OH (82.4 g) was added a solution of the above amine salt (54 mg) in dimethylformamide. Hydroxybenzotriazole (HOBT, 41.5 mg) N-methylmorpholine (21 mg) , and N' ,N'-dicyclohexylcarbodiimide (DCC 42.2 mg) were then added sequentially. After 2.5 h, the mixture was allowed to warm to room temperature for 16 h, at which time the mixture was filtered and evaporated to a residue which was partitioned between ethyl acetate and saturated NaHCO- . The organic phase was then washed separately with saturated NaHC0 3 and brine. Drying (Na,S0 4 ) and evaporation of the solvent provided the crude product. Chromatography on Si0 2 eluting with dichloromethane-methanol mixtures gave the desired compound (79 mg, 63%). Mass spectrum: M = 611. Example 139 Boc-His-Amide of 2-Amino-l-cyclohexyl- 3-hydroxy-6-methylheptane Following the procedure of Example 138, but replacing Boc-Phe-His-OH with Boc-His-OH, gave the desired compound in 47% yield. Example 140 Cbz-D-Ala-Phe-His Amide of 2-Amino- l-cyclohexyl-3-hydroxy-6-methylheptane Following the procedure of Example 138, but replacing Boc-Phe-His-OH with Cbz-D-Ala-Phe-OH and replacing the resultant compound of Example 137 with the resultant compound of Example 139 gave the desired product. Example 141 D-Ala-Phe-His Amide of 2-Amino- l-cyclohexyl-3-hydroxy-6-methylheptane The resultant compound of Example* 140- (1.0 g) in glacial acetic acid (20 L) was hydrogenated with 10% Pd/C (450 mg) at 55 p.s.i. H.. After 3 h, the mixture was filtered and evaporated. The residue was partitioned between ethyl acetate and saturated aqueous NaHC0 3 for 30 min. The organic phase was washed (brine), dried (Na 2 S0 4 ), filtered, and evaporated to give the desired compound in 84% yield. Example 142 D-Ser-Phe-His Amide of 2-Amino- l-cyσlohexyl-3-hydroxy-6-methylheptane Following the procedures of Examples 140 and 141, but replacing Cbz-D-Ala-Phe-OH with Cbz-D-Ser- Phe-OH, gave the desired product in 39% yield. Example 143 (OCH-.)Tyr-His Amide of 2-Amino- l-cyclohexyl-3-hydroxy-6-methylheptane Following the procedures of Examples 140 and 141, but replacing Cbz-D-Ala-Phe-OH with Cbz-(0CH 3 )- Tyr, gave the desired product. Example 144 (Imidazol-4-yl)acetyl-(QCH-)Tyr-His Amide of 2-Amino-l-eyelohexyl-3-hydroxy-6-methylheptane Following the procedure of Example 138, but replacing Boc-Phe-His-OH with (imidazol-4-yl)acetic acid, and replacing the salt derived from the resultant compound of Example 137 with the resultant compound of Example 143, gave the desired compound in 34% yield after recrystallization. Example 145 (Imidazol-l-yl)acetyl-(QCH 3 )Tyr-His Amide of 2-Amino-l-cyclohexyl-3-hydroxy-6-methylheptane The resultant compound of Example 143 (250 mg) in dry THF at 0°C was treated sequentially with 2 eq. N-methylmorpholine and 1 ^equivalent bromoacetyl bromide. After 1 h, imidazole (5 eq) was added. The mixture was warmed to room temperature for 6 h and then evaporated. Chromatography of the residue on silica gel (dichloromethane/isopropyl amine/methanol, 89:9:2) provided the desired product. Example 146 N-(2,3-dihydroxypropyl)Gly-(0CH 3 )Tyr-His Amide of 2-Amino-l-cyclohexyl-3-hydroxy-6-methylheptane Following the procedure of Example 145, but replacing imidazole with l-amino-2,3-dihydroxypropane provided the desired product. Example 147 4-t-Butyloxycarbonylamino-3-hydroxy-6-methyl-l-(4- methylvaleryl)amino-l-phenylheptane. To a stirred 0°C solution of N-benzylvaleramide (600 mg, 2.92 mmol) in dry THF (20 ml) was added butyl lithium (4.17 ml of a 1.32 M solution in hexane). The solution was cooled to -78°C and a solution of the resultant product of Example 49 (300 mg, 1.31 mmol) in THF (6 ml) was added dropwise. Saturated NH 4 C1 (20 ml) and water (20 ml) was added 1.5 h later. Ether (75 ml) and 1 M H 3 P0 4 (5 ml) were then added. The layers were separated, and the organic phase was washed with saturated NaHC0 3 (15 ml) and brine (15 ml). Drying and evaporating provided an oil which was chromatographed on 100 g Si0 2 with CH 2 Cl 2 /CH 3 OH mixtures to give 378 mg, 67% of the desired material. Mass spectrum: M + = 434. Example 148 Boc-Phe-Ala Amide of 4-Amino-3-hydroxy-6-methyl-l-(4- methylvaleryl)amino-1-phenylheptane■ Following the deprotection procedure of Example 138 and using the resultant compound of Example 147 gave the corresponding hydrochloride which was coupled to Boc-Phe-Ala according to the procedures of Example 16. The desired compound was obtained in 98% yield. Mass spectrum: .(M+H) = 653. Anal. calcd.: C, 68.1; H, 8.7; N, 8.6. Found: C 68.1; H. 9.0; 8.3. Example 149 4-t-Butyloxycarbonylamino-1-cyclohexyl- 3-hydroxy-6-methyl-l-(4-methylvaleryl) minoheptane The resultant compound of Example 147 (70.0 mg, 0.161 mmol) in glacial acetic acid (15 ml) was hydrogenated over Pt black (70 mg) for 22 h. The mixture was filtered, diluted with H 2 0 (50 ml) and brine (50 ml), and extracted with ethe (50 ml). The organic phase was washed with water (2 x 50 ml), saturated K 2 C0 3 . (25 ml), and brine (10 ml). Drying (MgS0 4 ) and evaporating gave 54 mg of the desired material. Mass spectrum: (M+H) + = 441. Anal, calcd.: C, 68.1; H, 11.0; N, 6.4. Found: C, 68.3; H, 11.5; N, 6.3. Example 150 Boc-Phe-Ala-amide of 4-Amino-l-cyclohexyl- 3-hydroxy-6-methyl-l-(4-methylvaleryl)aminoheptane Following the deprotection procedure of Example 138 and using the resultant compound of Example 149 gave the corresponding amine hydrochloride which was coupled to Boc-Phe-Ala according to the procedure of Example 16, " the desired compound was obtained in 89% yield. Mass spectrum: M + = 658. Example 151 5-t-Butyloxycarbonylamino-4-hydroxy-7-methyl- 2-phenyloctanoic Acid Isoamyl Amide Using the procedure of Example 147, but replacing 4-methylvaleric benza ide with N-isoamyl phenylacetamide gave the desired compound in 15% after chromatography. Example 152 Boc-Phe-Ala Amide of 5-Amino-4-hydroxy-7-methyl- 2-phenyloctanoic Acid Isoamyl Amide Following the deprotection procedure of Example 138 and using the resultant compound of Example 151 gave the corresponding amine hydrochloride which was coupled to Boc-Phe-Ala according to the procedure of Example 16. The desired compound was obtained in 75% yield. Mass spectrum: M + = 652. Anal. calcd. for C 3~ -7U.5_ _6U4.06_ C, 68.1; H, 8.7; N, 8.6. Found: C, 67.8; H, 8.7; N, 8.1. Example 153 5-t-Butyloxycarbonylamino-2-cyclohexyl- 4-hydroxy-7-methyloctanoicAcid Isoamyl Amide The resultant compound of Example 151 was hydrogenated according to the procedure of Example * 149 to give the desired compound in 68% yield. Example 154 Boc-Phe-Ala Amide of 5-Amino-2-cyclohexyl- 4-hydroxy-7-methyloctanoic Acid Isoamyl Amide Following the deprotection of Example 138 and using the resultant compound of Example 153 gave the corresponding amine hydrochloride which was coupled to Boc-Phe-Ala according to the procedure of Example 16. The desired compound was obtained in 82% yield. Example 155 4-t-Butyloxycarbonylamino-3-hydroxy- 6-methylheptanoic Acid Ethyl Ester To diisopropylamine (7.7 g, 0.077 mol) in dry tetrahydrofuran (20 ml) cooled to -20°C under an argon atmosphere was added dropwise n-butllithium in hexane (1.46 M, 52.4 ml, 0.077 mol). The solution was stirred 15 min, the temperature lowered to -78°C and dry ethyl acetate (6.7 g, 0.077 mol) added dropwise while maintaining the temperature below -75°C. The solution was stirred 10 min and a precooled (-78°C) tetrahydrofuran solution of Boc-L-leucinal (11 g, 0.051 mol) was added. After 30 min, 2 M HCl (40 ml) was added and the mixture was slowly warmed to 10°C and extracted with ether (3 x 200 ml) . The combined ethereal extract was washed with satd. sodium chloride (NaCl) and r dried with magnesium sulfate (MgS0 4 ) and filtered. Evaporation of the filtrate in vacuo gave 14 g of crude product which was purified by flash column chromatography (20% ethylacetate in hexane) . Obtained 6 g of Boc-Sta-OEt. H' NMR (300 MHz, CDC1 3 , ppm), 0.93 (d,6H), 1.27 (t,3H), 1.3-1.75 (m,3H), 1.44 (S,9H), 2.50 (m,2H), 3.35 (s,lH), 3.63 (br m-lH), 4.03 (br m,lH), 4.18 (q,2H), 4.75 (br d,lH). Example 156 4-t-Butyloxycarbonylamino-3-hydroxy- 6-methylheptanoic Acid (Boc-Statine) To 0.8 g of Boc-Sta-OEt in 24 mi of dioxane/water (2:1) was added 120 mg of lithium hydroxide at 0°C. After 10 min, the mixture was warmed to room temperature. After 1 h, the mixture was poured to a 10% solution of potassium bisulfate and extracted with ethyl acetate (3 x 100 ml). The combine organic phase was washed with a satd. NaCl solution and dried with MgS0 4 and filtered. Evaporation of the filtrate in vacuo gave 0.7 g of a white solid. Recrystallization from ether/hexane gave a solid with a m.p.of 117-118°C. Example 157 Boc-Sta Amide of Benzyl Amine To a solution of 340 mg of Boc-Sta in 25 ml of tetrahydrofuran at -20°C was added 183 uL (1.25 eq. ) of N-methylmorpholine, followed by 216 uL (1.25 eg.) of isobutylchloroformate. The solution was stirred for 5 min at which time 300 uL (excess) of benzyl amine was added. After 15 min at -20°C, the solution was warmed to 0°C* for 30 min. The solid was filtered and the filtrate was evaporated in vacuo. The residual oil was dissolved in ethyl acetate (50 ml) and washed with 10 ml of 10% potassium bisulfate solution. The aqueous phase was extracted with ethyl acetate (2 x 50 ml) and the combined ethyl acetate solution was washed with satd. NaCl solution and dried with MgS0 4 . Evaporation in vacuo gave a colorless oil which upon purification by silica gel column chromatography (5% MeOH/95% CH 2 C1 2 ) gave 370 mg (82%) of pure product as a colorless oil. Mass spectrum: M + = 364 NMR (60 MHz, CDC1 3 , ppm); 0.95 (d,6H), 1.45 (S,9H), 1.35-1.55 (m,3H), 2.4 (d,2H), 3.4-4.4 (m,5H), 4.8 (br d,lH), 6.9 (br d,lH), 7.25 (s,5H). Example 158 Boc-Sta Amide of Isobutylamine Using the procedure of Example 157, but replacing benzylamine with isobutylamine gave the' desired compound (87% yield) . Mass spectrum: M = 330. Example 159 Boc-Sta Amide of Isopentylamine Using the procedure of Example 157, but replacing benzylamine with isopentylamine gave the desired compound (81% yield). Mass spectrum: M = 344. Example 160 Boc-Sta Amide of 2-Methylbutylamine Using the procedure of Example 157, but replacing benzylamine with 2-methylbutylamine gave the desired compound (86% yield). Mass spectrum: M + = 344. Example 161 Boc-Sta Amide of Isoleucinol Using the procedure of Example 157, but replacing benzylamine with isoleucinol gave the desired compound (85% yield). Mass spectrum: M + = 374. Example 162 Boc-Sta Amide of Methioninol Using the procedure of Example 157, but replacing benzylamine with methioninol gave the desired compound (83% yield). Mass spectrum: M = 392. Example 163 Amine Hydrochloride of Boc-Sta Amide of Benzyl Amine Boc-Sta amide of benzylamine (100 mg, 0.27 mmol) was dissolved in 3 ml of 4N HCl and stirred for 10 min. The solvent was evaporated in vacuo and the crude product, the amine hydrochloride from deprotection of the N-terminal of Boc-Sta-amide of benzylamine was dried under high vacuum for 12 h at room temperature. Likewise, the amine hydrochloride of the compounds in Example 158 to Example 161 are prepared by the same procedure. Example 164 Boc-Phe-His-Sta Amide of Benzylamine To the amine hydrochloride of Boc-Sta amide of benzylamine (200 mg, 0.34 mmol) in 4 ml of dimethyl formamide (DMF) was added triethylamine (47 uL, 0.34 mmol). The solution was cooled to 0°C and Boc-Phe-His-OH was added (136 mg, 0.34 mmol), followed by 1-hydroxybenzotriazole (70 mg, 0.51 mmol) and then dicyclohexylcarbodiimide (72 mg, 0.34 mmol). The solution was stirred at 0°C for 8 h and then at room temperature for 4 h. The solution was filtered and the solvent was evaporated under vacuum. The residual solid was dissolved in ethyl acetate (50 ml) and washed with satd. sodium bicarbonate and then satd. sodium chloride solution, dried with MgS0 4 , filtered and the solvent evaporated in vacuo. The crude product was purified by silica gel column (8% MeOH:92% CH 2 C1 2 ) and 110 mg (50%) of product was obtained. m.p. 169°-170°C. Mass spectrum: M = 648. Anal. calcd. for C 35 H 4 _N 6 0 6 : C, 64.79; H, 7.46; N, 12.95. Found: C, 64.56; H, 7.40; N, 12.81. Example 165 Boc-( α-Naphthyl)-Ala-Ala-Sta Amide of Benzylamine To the amine hydrochloride of Boc-Sta amide of benzylamine (100 mg, 0.34 mmol) in THF (3 ml) was added triethylamine (47 uL, 1 equivalent). This solution was added to the mixed anhydride of Boc-(α -NaphthyDAla- Ala-OH generated at -20°C in the following manner To Boc-( α-NaphthyDAla-Ala-OH (130 mg, 0.34 mmol) in 7 ml of THF at -20°C was added N-methylmorpholine (0.34 mmol), followed by isobutylchloroformate (0.34 mmol). The generation of the mixed anhydride was complete in 5-10 min. The reaction mixture was stirred at -20°C for 2 h then at 0°C for 30 min. It was poured into a 10% solution of potassium bisulfate (40 ml) and extracted with ethyl acetate (50 ml x 3). The combined ethyl " acetate solution was washed with satd. sodium bicar¬ bonate (40 ml) and then brine (40 ml), dried with MgS0 4 , and filtered. The solvent was evaporated in vacuo. The residual oil was purified by silica gel column (5% MeOH:95% CH 2 C1 2 ) to give 140 mg of product (65% yield). m.p. 95°-96°C. Mass spectrum: (M + H) + = 699. Example 166 Boc-Phe-His-Sta Amide of Isobutylamine Using the procedure of Example 164, but using the amine hydrochloride of Boc-Sta amide of isobutyl¬ amine gave the desired compound (60% yield). m.p. 163-164°C. Mass spectrum: (M+H) + = 615. Example 167 Boc-( t-Naphthyl)Ala-Ala-Sta Amide of Isoleucinol Using the procedure of Example 165, but using the amine hydrochloride of Boc-Sta amide of iso¬ leucinol gave the desired compound (81% yield), m.p. 181-182°C. Mass spectrum: (M+H) + = 643. Example 168 Boc-( α-Naphthyl)Ala-Ala-Sta Amide of Methioninol Using the procedure of Example 165, but using the amine hydrochloride of the Boc-Sta amide of methioninol gave the desired product (76% yield). m.p. 183-184°C. Mass spectrum: (M+H) + = 661. Example 169 Boc-His-Sta Amide of 2-Methylbutylamine Using the procedure of Example 164, but using the amine hydrochloride of Boc-Sta amide of 2-methyl- butylamine and replacing Boc-Phe-His with Boc-His-OH gave the desired compound (60% yield). m.p. 115-116°C. Mass spectrum: M = 681 L. Example 170 t-Butylacetyl-Phe-His-Sta Amide of 2-Methylbutylamine Using the procedure of 165, but using the amine hydrochloride of Example 169 and replacing Boc( -Naph- thyl)-Ala-Ala-OH with t-butylacetyl-Phe-OH gave the desired compound (45% yield). m.p. 186-188°C. Mass spectrum: (M+H) = 627. Example 171 Boc-p-iodo-Phe-His-Sta Amide of 2-Methylbutylamine Using the procedure of Example 165, but using the amine hydrochloride of Example 169 and replacing Boc ( " -Naphthyl ) -Ala-Ala-OH with Boc-p-iodo-Phe-OH gave the desired compound (65% yield). m.p. 213°C (decomp.). Mass spectruumrn:: ((MM++HH)) + = 755 Example 172 4-t-Butyloxycarbonylamino-5-phenyl- 3-hydroxypentanoic Acid Ethyl Ester (Boc-F-Sta Ethyl Ester) Using the procedure of Example 155, but replacing Boc-L-leucinal with Boc-L-phenylalaninal gave the desired compound (52% yield). Mass spectrum: M + = 337. Example 173 4-t-Butyloxycarbonylamino-5-phenyl- 3-hydroxypentanoic Acid (Boc-F-Sta) Using the procedure of Example 156 but using the compound in Example 172 gave the desired compound (95% yield) . m.p. 88°C. Example 174 Boc-F-Sta Amide of Isopentylamine Using the procedure of example 157, but replacing Boc-Sta with Boc-F-Sta and replacing benzyl¬ amine with isopentylamine gave the desired compound (75% yield), m.p. 157-158°C. Mass spectrum: M + = 378. Example 175 Boc-Phe-His-F-Sta Amide of Isopentylamine Using the procedure of Example 164, but using the amine hydrochloride of Boc-F-Sta amide of isopentyl¬ amine gave the desired compound (51% yield). m.p.- 201-202°C. Mass spectrum: (M+H) + = 663. Example 176 4-t-3utyloxycarbonylamino-3-hydroxy- 5-cyclohexylpentanoic Acid Ethyl Ester (Boc-ACHPA Ethyl Ester) Using the procedure of Example 155, but replacing Boc-Leucinal with Boc-Cyclohexylalaninal gave the desired compound in 40% yield. Mass spectrum: M + = 343 . Example 177 4-t-Butyloxycarbonylamino-3-hydroxy- 5-cyclohexylpentanoic Acid (Boc-ACHPA) Using the procedure of Example 156, but using the compound from Example 176, gave the desired compound (100% yield). Mass spectrum: M + = 315. Example 178 Boc-ACHPA Amide of Isopentylamine Using the procedure of Example 157, but replacing Boc-Sta with Boc-ACHPA and benzyl amine with isopentylamine gave the desired compound (70% yield). Mass spectrum: M + = 384. Example 179 Boc-Phe-His-ACHPA Amide of Isopentylamine Using the procedure of Example 164, but using the amine hydrochloride of Boc-ACHPA amide of isopentylamine gave the desired compound (42% yield) . m.p. 108-110°C. Mass spectrum: (M + H) = 669. Example 180 4-t-Butyloxycarbonylamino-2-benzyloxy-3-hydroxy- 5-cyclohexylpentanoic Acid Methyl Ester Using the procedure of Example 155, but replacing Boc-leucinal with Boc-cyclohexylalaninal, and replacing ethyl acetate with benzyloxymethyl acetate gave the desired compound in 14.5% yield. Mass spectrum: M + = 435. Example 181 4-t-Butyloxycarbonylamino-2-benzyloxy-3-hydroxy- 5-cyclohexylpentanoic Acid Using the procedure of Example 156, but using the compound from Example 180 gave the desired compound (100% yield). Mass spectrum: M + = 431. Example 182 4-Boc-amino-2-benzyloxy-3-hydroxy-5-cyclohexyl- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 157, but replacing Boc-Sta with the compound in Example 181 and benzyl amine with 2-methylbutylamine gave the desired compound (72% yield). Mass spectrum: M = 490. Example 183 4-3oc-amino-2,3-dihydroxy-5-cyclohexyl- pentanoic Acid Amide of 2-Methylbutylamine A solution of 400 mg of the compound in Example 182 in 20 ml of methanol with 200 mg of palladium black added was stirred vigorously under 3 atmosphere of hydrogen for 17 h. The catalyst was filtered off and the solution was concentrated in vacuo. The crude product was purified by silica gel chromatography to give 203 mg (62% yield) of desired product. Mass spectrum: M = 400. Example 184 Amine Hydrochloride of 4-Boc-amino-2-benzyloxy- 3-hydroxy-5-cyclohexyl-pentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 163, but replacing Boc-Sta amide of benzylamine with the compound is Example 182 gave the desired product (100% yield). Example 185 Amine Hydrochloride of 4-Boc-amino-2,3-dihydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine '" Using the procedure in Example 163 but replacing Boc-Sta amide of benzylamine with the compound in Example 183 gave the desired product (100% yield). Example 186 3oc-Phe-Alaninyl-4-amino-2-benzyloxy- 3-hydroxy-5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure- of Example 165, but replacing Boc-( α-Naphthyl)-Ala-Ala-OH with Boc-Phe- Ala-OH and using the amine hydrochloride in Example 184 gave the desired product (59% yield). Mass spectrum: (M+H) + = 709. Example 187 Boc-Phe-Histidinyl-4-amino-2-benzyloxy-3-hydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 166, but using the amine hydrochloride in Example 184 gave the desired product (40% yield). Mass spectrum: (M+H) = 776. Example 188 Boc-Phe-Alaninyl-4-amino-2,3-dihydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 165, but replacing Boc-(α -Naphthyl)-Ala-Ala-OH with Boc-Phe- Ala-OH and using the amine hydrochloride in Example 185 gave the desired product. Mass spectrum: (M+H) = 619. Example 189 Boc-Phe-Histidinyl-4-amino-2,3-dihydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure in Example 165, but using the amine hydrochloride in Example 185 gave the desired product (35% yield). Mass spectrum: (M+H) + = 685. Example 190 4-t-Butyloxycarbonylamino-2-methoxy-3-hydroxy- 5-cyclohexylpentanoic Acid Ethyl Ester Using the procedure of Example 155 but- replacing Boc-Leucinal with Boc-cyclohexylalaninal, and replacing ethyl acetate with methoxy ethyl acetate gave the desired product (33% yield) . Mass spectrum: M = 407. Example 191 4-t-Butyloxycarbonylamino-2-methoxy-3-hydroxy- 5-cyclohexylpentanoic Acid Using the procedure of Example 156, but using the compound from Example 190 gave the desired product (100% yield). Mass spectrum: M + = 379. Example 192 4-Boc-ammo-2-methoxy-3-hydroxy-5-cyclohexyl- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 157, but replacing Boc-Sta with the compound in Example 191 and benzyl amine with 2-methylbutyl mine gave the desired product (80% yield). Mass spectrum: (M+H) + = 449. Example 193 Amine Hydrochloride of 4-Boc-ammo-2-methoxy- 3-hydroxy-5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 163, but replacing Boc-Sta amide of benzyl amine with the compound in Example 192 gave the desired compound (100% yield) . Example 194 Boc-Phe-Histidinyl-4-amino-2-methoxy-3-hydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 164, but using, the amine hyrochloride in Example 193 gave the desired product (35% yield). Mass spectrum: (M+H) + = 699. Example 195 4-t-Butyloxycarbonylamino-2-allyl-3-hydroxy- 5-cyclohexylpentanoic Acid Ethyl Ester Using the procedure of Example 155, but replacing Boc-Leucinal with Boc-cyclohexylalaninal, and - replacing ethyl acetate with ethyl-4-pentenoate gave the desired product in 55% yield. Mass spectrum: M = 383. Example 196 4-t-Butyloxycarbonylamino-2-allyl-3-hydroxy- 5-cyclohexylpentanoic Acid Using the procedure of Example 156, but using the compound from Example 195 gave the desired compound (100% yield). Mass spectrum: M' = 355. Example 197 4-Boc-amino-2-allyl-3-hydroxy-5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 164, but replacing Boc-Phe-His-OH with the compound in Example 196 and using 2-methylbutylamine instead of an amine hydrochloride gave the desired product (50% yield) -*- Mass spectrum: M = 424 _ . Example 198 Amine Hydrochloride of 4-t-Boc-amino-2-allyl- 3-hydroxy-5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 167, but replacing Boc-Sta amide of benzylamine with the compound in Example 59 gave the desired compound (100% yield). Example 199 Boc-Phe-Histidinyl-4-amino-2-allyl-3-hydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 164, but using the amine hydrochloride in Example 199 gave the desired product (40% yield). Maassss ssppeeccttrruumm: (M+H) + = 709 Example 200 Boc-Phe-Histidinyl-4-amino-2-propyl-3-hydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine A solution of 11 mg of the compound of Example 199 in methanol with 3 mg of 10% palladium on charcoal added was stirred vigorously under hydrogen atmosphere " for 2 h at room temperature. The catalyst was filtered off and the filtrate concentrated to give a colorless oil. Purification by silica gel column chromatography gave 11 mg of pure product (100% yield). Mass spectrum: (M+H) + = 711. Example 201 Boc-Phe-Methioninyl-4-amino-2-methoxy-3-hydroxy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 165, but replacing Boc-( α-Naphthyl)-Ala-Ala-OH with Boc-Phe- Met-OH and using the amine hydrochloride in Example 193 gave the desired compound (80% yield). Mass spectrum: (M+H) + = 693. Example 202 Boc-Phe-S-methyleysteinyl-4-amino-2-methoxy-3-hydroxy- 5-cvclohexlpentanoic Acid Amide of 2-Methylbutyl mine Using the procedure of Example 165, but replacing Boc-( α-Naphthyl)-Ala-Ala-OH with Boc-Phe- S-methylcysteine and using the amine hydrochloride in Example 193 gave the desired compound (63% yield). Mass spectrum: (M+H) + = 679. Example 203 Boc-Phe-Alaninyl-4-ammo-2-allyl-3-hydroxy- 5-cyclohexylpentanoicAcid Amide of 2-Methylbutyl mine Using the procedure of Example 165, but replacing Boc-( α-Nap thyl)-Ala-Ala-OH with Boc-Phe- Ala-OH and using the amine hydrochloride in Example 198 gave the desired compound (56% yield). Mass spectrum: (M+H) + = 643. Example 204 Boc-Phe-S-methylcysteinyl-4-amino-2-allyl-3-hydroχy- 5-cyclohexylpentanoic Acid Amide of 2-Methylbutylamine Using the procedure of Example 165, but ' replacing Boc-(α -Naphthyl)-Ala-Ala-OH with Boc-?he- S-methylcysteine and using the amine hydrochloride in Example 198 gave the desired compound (52% yield). Mass spectrum: (M+H) + = 689. Example 205 2-Benzyloxycarbonylamino-l,4-butanediol To 15 g of N-benzyloxycarbonyl L-aspartic acid in 250 ml of tetrahydrofuran at 0°C was added two equivalents of BH'THF (1 M) . The solution was stirred at 0°C for 30 min and then at room temperature for 3.5 h. The reaction was carefully quenched with cold water. The product was extracted with ethyl acetate (3 x 300 ml) and the combined organic phase washed with brine and dried with anhydrous MgS0 4 . Filtration and concentration gave an oil which was purified by silica gel column chromatography (10% MeOH/CH 2 Cl 2 ) to give 7.1 g of white solid. Mass spectrum: M + .= 239. Example 206 4-Hyd oxyethy1-oxazo1idin-2-one To 1.1 g of the compound in Example 204 in 25 ml of DMF at 0°C was added 360 mg of sodium hydride (60% oil dispersion) portionwise. At the end of the addition, the suspension was stirred at 0°C for 2 h and then at room temperature overnight. The solvent was evaporated under reduced pressure. The crude oily product was purified by silica gel column chromatography (10% MeOH/CH 2 Cl 2 ) to give 580 mg of white solid, m.p. 90-91°C. Mass spectrum: M + = 131. Example 207 (Oxazolidin-2-one-4-yl)ethanal To 520 mg of the product from Example 206 in 110 ml of CH 2 C1 2 was added 2.1 g of pyridinium dichromate. The suspension was stirred at room temperature overnight. The reaction mixture was filtered through a thightly packed layer of celite an " concentrated under reduced pressure. The crude brown oil was purified by silica gel column chromatography (5% MeOH/CH 2 Cl 2 ) to give 270 mg of pure aldehyde. Mass spectrum: M + = 129. Example 208 4-[ (1,3-Dithiolan-2-yl)methyl]oxazolidin-2-one To a solution of 370 mg of the aldehyde from Example 207 in 30 ml of dichloromethane was added 0.48 ml of 1,2-ethanedithiol . To this solution at 0°C was added 2 drops of boron trifluoride-ether complex. The solution was stirred at 0°C for 10 min and then at room temperature for 20 min. TLC analysis showed no aldehyde was left. The solution was concentrated and the crude oily residue was purified by silica gel column chromatography (CH 2 Cl 2 /EtOAc 1:1) to give 270 mg of product. Mass spectrum: M = 205. Example 209 4-[(1 ' ,3 '-Dithian-2'-yl)methyl]oxazolidin-2-one Using the procedure of Example 208, replacing 1,2-ethanedithiol with 1,3-propane-dithiol gave the desired product (70%). Mass spectrum: M = 219. Example 210 4-[ (1 ' ,3 '-Dioxolan-2'-yl)methyl]oxazolidin-2-one To 320 mg of the aldehyde from Example 207 in 25 ml of benzene was added 1 ml of ethylene glycol and 10 mg of p-toluenesulfonic acid. The solution was heated to reflux for 1 h and cooled to room temperature. It was washed with satd. sodium bicarbonate solution and extracted with ethyl acetate (3 x 50 ml). The organic phase was dried with anhydrous MgS0 4 , filtered and concentrated under reduced pressure. Purification of the crude product by silica gel column chromatography (5% MeOH/CH 2 Cl 2 ) gave 2 21133 img of the desired product. Mass spectrum: M 173. Example 211 4-C (1 ' ,3 '-Dioxan-2 '-yl)methyl]oxazolidin-2-one Using the procedure of Example 210, replacing ethylene glycol with 1,3-propanediol gave the desired product (53%). Mass spectrum: M + = 187. Example 212 2-t-Butyloxycarbonylamino- 3-(l' ,3 '-dithiolan-2'-yl)-propanol To 360 mg of the product from Example 208 in ethanol/water (25 ml/25 ml) was added 785 mg of barium hydroxide (2 equivalents). The suspension was heated to reflux for 16 h. Upon cooling to room temperature, the solid formed was filtered and washed with methanol. The solution was concentrated under reduced pressure. The residue was dissolved in 20 ml of dichloromethane. To this solution was added 1.5 equivalents of di-t- butyldicarbonate. After 2 h, the solvent was removed under reduced pressure and the crude product was purified by silica gel column chromatography (CH 2 Cl 2 /EtOAc 6.4) to give 430 mg of pure product. Mass spectrum: M = 279. Example 213 2-t-Butyloxycarbonylammo- 3-( 1 ' , 3 ' -dithian-2 ' -yl )-propanol Using 110 mg of the product from Example 209 and the procedure in Example 212 gave 90 mg of the desired product. Example 214 2-Benzyloxycarbonylamino- 3-(l ' ,3 '-dioxolan-2'-yl)-propanol To 200 mg of the oxazolidinone from Example HS-56 in dioxane/ water (15 ml/15 ml) was added 400 mg of barium hydroxide (2 equivalents). The suspension was heated to reflux for 3.5 h, at which time all the starting material was consumed. The suspension was cooled to room temperature and filtered. The solid was washed with methanol and the solution was concentrated " under reduced pressure. The residue was dissolved in 10 ml of dichloromethane and 1.5 equivalents of N-(benzyloxycarbonyloxy)-succinimide was added. After 1 h, the solution was concentrated under reduced pressure and the crude product was purified by silica gel column chromatography (5% MeOH/CH Cl ) to give 305 mg of the desired product. Mass spectrum: M = 281, m.p. 85-86°C. Example 215 2-Benzyloxycarbonylamino-3-(l' ,3 '-dioxan-2'-yl)-propanol Using 300 mg of the product from Example 211 and using the procedure of Example 214 gave 280 mg of the desired product. Example 216 3-hydroxy-4-t-Butyloxycarbonylamino- 5-(l' ,3 '-dithiolan-2'-yl)-pentanoic Acid Ethyl Ester To a solution of 0.28 ml of DMSO in 15 ml of dichloromethane at -78°C was added 0.24 ml of oxalyl chloride. After 5 min, a solution of 430 mg of the product from Example 219 in 20 ml of dichloromethane was added. After stirring at -78°C for 20 min, 1.6 ml of triethylamine was added and the solution stirred for another 20 min. It was poured into a 10% aqueous solution of potassium hydrogen sulfate. After separation of the organic phase, the aqueous phase was extracted with dichloromethane (2 x 100 ml). The combined organic solution was washed with water (3 x 50 ml) and then saturated NaCl solution and then dried with anhydrous sodium sulfate. The solution was filtered and concentrated under reduced pressure. The residual oily product as dried under high vacuum for 2 h at room temperature. It was then dissolved in 15 ml of THF and added at -78°C to 2.75 equivalents of lithio ethyl acetate generated in the following manner: (To 0.59 ml of diisopropyl amine in 1.5 ml of THF at -78°C was added 1 equivalent of a hexane solution of n-butyl-- lithium (1.6 M) . After 15 min, 0.41 ml of dry ethyl acetate was added and the solution was stirred at -78°C for 20 min. After The reaction was quenched with 10% potassium hydrogen sulfate solution after 30 min. The aqueous phase was extracted with ethyl acetate (3 x 100 ml) and the combined organic phase was dried with anhydrous MgSO d ) . It was filtered and concen¬ trated under reduced pressure to give a pale yellow oil which was purified by silica gel column chromatography (20% ΞtOAc/80% CH 2 C1 2 ) to give 258 mg of the desired product. Mass spectrum: M = 365. Example 217 3-Hydroxy-4-t-butyloxycarbonylamino- 5-(1' ,3 '-dithian-2 '-yl)-pentanoic Acid Ethyl Ester Using the same sequence of reactions outlined in Example 216 and using 140 mg of the product from Example 213 as the starting material provided 57 mg of the desired product after silica gel column chromatog¬ raphy. (CH 2 Cl 2 /EtOAc 2:8). Mass spectrum: M + 379. Example 218 3-Hydroxy-4-benzyloxyca bonylamino- 5-(l' ,3 '-dioxolan-2'-yl)-pentanoic Acid Ethyl Ester Using the same sequence of reactions outlined in Example 216 and using 270 mg of the product from Example 214 as the starting material gave 210 mg of the desired product after silica gel column chromatography (CH 2 Cl 2 /EtOAc 1:1). Mass spectrum: M + = 333. Example 219 3-Hydroxy-4-benzyloxycarbonylamino- 5-(l' ,3 '-dioxan-2'-yl)-pentanoic Acid Ethyl Ester Using the same sequence of reactions outlined in Example 216 and using 274 mg of the product from Example 215 as starting material gave 200 mg of the desired product after silica gel column chromatography (CH 2 Cl 2 /EtOAc 6:4). Mass spectrum: M + = 347. Example 220 3-Hydroxy-4-t-butyloxycarbonylamino- 5-(1 ' ,3 '-dithiolan-2'-yl)-pentanoic Acid To a solution of 250 mg of the product from Example 216 in 6 ml of dioxane/water (1:1) was added 1.2 equivalents of lithium hydroxide. The solution was stirred at room temperature for 30 min. The solution was acidified with 10% potassium hydrogen sulfate solution and extracted with ethyl acetate (3 x 50 ml) dried with anhydrous MgS0 4 and filtered. The solution was concentrated under reduced pressure to afford 248 mg of a gummy white solid which is used without further purification. Mass spec :ttrruumm:: MM = ***• 337. Example 221 3-Hydroxy-4-t-butyloxycarbonylamino- 5-(l ' ,3 '-dithian-2 '-yl)-pentanoic Acid Using the procedure described in Example 220 and using 50 mg of the product from Example 217 as starting material gave 49 mg of the desired product. Mass spectrum: M = 351 L. Example 222 3-Hydroxy-5-benzyloxycarbonylamino- 5-(l' ,3 '-dioxolan-2 '-yl)-pentanoic Acid Using the procedure described in Example 220 and using 200 mg of the product for Example 219 as the starting material gave 147 mg of the desired product. Mass spectrum: M = 305 Example 223 3-Hydroxy-5-benzyloxycarbonylammo- 5-(l' ,3 '-dioxan-2'-yl)-pentanoic Acid Using the procedure described in Example 220 and using 200 mg of the product from Example 219 as the starting material gave 200 mg of the desired product. Mass spectrum: M = 319 3. Example 224 3-Hydroxy-4-t-butyloxycarbonylamino- 5-(l ' ,3 '-dithiolan-2'-yl)-pentanoic Acid Amide of 2-Methylbutyl Amine To a solution of 250 mg of the product from Example 220 in 30 ml of dry THF at -15°C was added 0.13 ml of N-methylmorpholine, followed by 0.155 ml of isobutylchloro-formate. After stirring for 10 min, 0.25 ml of (S)-2-methylbutylamine was added. The reaction was complete after 20 min and was poured into 10% potassium hydrogen sulfate solution and extracted with ethyl acetate (3 x 50 ml), dried with anhydrous MgS0 4 and filtered. The solution was concentrated under reduced pressure to give a pale yellow oil which was purified by silica gel column chromatography (2% MeOH/CH 2 Cl 2 ) to give 200 mg of pure product. Mass spectrum: M = 406. Example 225 3-Hydroxy-4-t-butyloxycarbonylamino- 5-(1 ' ,3 '-dithian-2'-yl)-pentanoic Acid Amide of 2-methylbutylamine Using the procedure described in Example 224 and using 50 mg of the product from Example 221 as the starting material gave 49 mg of the desired product after silica gel column chromatography (3% MeOH/ CH 2 C1 2 ). Mass spectrum: M + = 420. Example 226 3-Hydroxy-4-benzyloxycarbonylamino- 5-(l ' ,3 '-dioxolan-2 '-yl)-pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 224 and using 147 mg of the product from Example 222 as the starting material gave 124 mg of the desired product after silica gel column chromatography (2% MeOH/ CH 2 C1 2 ). Mass spectrum: M + = 408. Example 227 3-Hydroxy-4-benzyloxycarbonylamino- 5-(l' ,3'-dioxan-2'-yl)- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 224 and using 200 mg of the product from Example 223 as the. starting material gave 190 mg of the desired product after silica gel column chromatography (2% MeOH/ CH 2 C1 2 ) . Mass spectrum: M + = 422. Example 228 Amine Hydrochloride of 3-hydroxy- 4-t-butyloxycarbonylamino-5-(1 ' ,3 '-dithiolan-2'-yl)- pentanoic Acid Amide of 2-Methylbutylamine To 0.2 g of the product from Example 224 was added 8 ml of 4N HCl in dioxane. The solution was stirred at room temperature for 30 min and the solvent was then removed under reduced pressure to give a gummy solid which was used without further purification. Example 229 Amine Hydrochloride of 3-hydroxy- 4-t-butyloxycarbonylamino-5-(1 ' ,3 '-dithian-2'-yp- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 228 and using the product from Example 225 gave the desired product which was used without further purification. Example 230 3-Hydroxy-4-amino-5-(l ' ,3 '-dioxolan-2'-yp- pentanoic Acid Amide of 2-Methylbutylamine To 124 mg of the product from Example 226 in a 50 ml roundbottom flask was added 10 mg of 10% palladium on charcoal. To this was added carefully 10 ml of methanol. The suspension was stirred vigorously under a hydrogen atmosphere by attaching a 3-way stopcock with a hydrogen-filled balloon attached. Reaction was complete in 10 min as shown by the complete disappearance of the starting material on TLC analysis. The suspension was filtered and the catalyst was washed with 20 ml of "* methanol. The combined methanol solution was concentrated under pressure to give the desired product which was used without further purification. Example 231 3-Hydroxy-4-amino-5-(l ' ,3 '-dioxan-2'-yl)- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 230 and using the product from Example 227 as the starting material gave the desired product which was used without further purification. Example 232 Boc-Phe-S-methylcysteinyl-[3-hydroxy-4-ammo- 5-(l ' ,3 '-dithiolan-2 '-yl) ]-pentanoic Acid Amide of 2-Methylbutylamine To a solution of 57 mg of Boc-Phe-S-methyl- cysteine in 5 ml of THF at -15°C was added 0.017 ml of N-methylmorpholine, followed by 0.020 ml of isobutyl- chloroformate. After 10 min, a solution of the product from Example 228 (starting with 49 mg) in 5 ml of THF with 0.016 ml of N-methylmorpholine was added. After the solution was stirred at -15°C for 1 h, it was poured into 10% potassium hydrogen sulfate and extracted with ethyl acetate (3 x 50 ml), dried with anhydrous MgS0 4 and filtered. The solvent was evaporated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (CH 2 Cl 2 /EtOAc 3:7) to give 36 mg of product. Mass spectrum: (M + H) + = 671; m.p. = 144-145°C. Example 233 Boc-Phe-S-methylcysteinyl- [3-hydroxy-4-amino-5-(l' ,3 '-dithian-2'-yl) 3- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 232 and using 57 mg of Boc-Phe-S-methyl-cysteine and the product from Example 229 (from 44 mg of starting material) gave 25 mg of the desired product after silica " gel column chromatography (CH 2 Cl 2 /EtOAc 3:7). Mass spectrum: (M+H) + = 685. Example 234 Boc-?he-S-methylcysteinyl- [3-hydroxy-4-amino-5-(1 ' ,3 '-dioxolan-2 '-yl) ] - pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 232 and using 63 mg of Boc-Phe-S-methylcysteine, 40 mg of the product from Example 230, gave 51 mg of the desired product after silica gel column chromatography (2% MeOH/CH 2 Cl 2 ) . Mass spectrum: (M+H) + = 639. Example 235 Boc-Phe-S-methylcysteinyl- [3-hydroxy-4-amino-5-(l ' ,3 '-dioxan-2'-yl) ]- pentanoic Acid Amide of 2-Methylbutylamine Using the procedure described in Example 232 and using 40 mg of Boc-Phe-S-methylcysteine, 40 mg of the product from Example 231 gave 40 mg of the desired product after silica gel column chromatography (2% MeOH/CH 2 Cl 2 ) . Mass spectrum: (M+H) + = 653. Example 236 Ethoxycarbonyl-Phe-Leu- [3-hydroxy-4-amino-5-(l' ,3'-dioxan-2'-yl) ]- pentanoic Acid Amide of 2-Methylbutyl mine Using the procedure described in Example 232 and using 42 mg of the ethoxycarbonyl-Phe-Leu, 35 " mg of the product from Example 231 gave 36 mg of product after silica gel column chromatography (2% MeOH/CH 2 Cl 2 ) . Mass spectrum: (M+H) + = 621. Example 237 Boc-Phe-His-[3-hydroxy-4-amino- 5-(l' ,3'-dithiolan-2'-yl)3- pentanoic Acid Amide of 2-Methylbutylamine To a solution of 47 mg of Boc-Phe-His-OH in 5 ml of DMF at -15°C was added sequentially 45 mg of 1-hydroxybenzotriazole, 21 mg of ethyl dimethylamino-" propyl carbodiimide. After 1 h at -15°C, a solution of 37 mg of the product from Example 228 in .3 ml of DMF was added. The solution was kept at -15°C for several hours and then at room temperature overnight. The solvent was removed under reduced pressure and the residue was washed with saturated sodium bicarbonate and extracted with ethyl acetate (3 x 50 ml), dried with anhydrous MgS0 4 and filtered. The solution was concentrated under reduced pressure and the crude product was purified by silica gel column chromatography (5% MeOH/CH 2 Cl 2 ) to give 12 mg of product. Mass spectrum: (M+H) + = 691. Example 238 2(R,S)-(4-morpholinylcarbonylmethyP- 3-(1 '-naphthyp-propionic Acid To 50 ml of absolute ethanol was added 2 g of sodium metal. The suspension was stirred vigorously until all the sodium dissolved and the evolution of hydrogen ceased. To this solution of sodium ethoxide was added a solution of 11.6 g of diethylsuccinate in 10.4 g of 1-naphthaldehyde. The solution was heated to reflux for 3 h, . at which time it was cooled to room temperature and concentrated on the rotavap. The residue was dissolved in 320 ml of water and extracted 6 times with 100 ml portions of ether. The aqueous layer was acidified with 2N HCl and extracted with 2 x 300 ml of ether and dried with anhydrous magnesium sulfate. Evaporation of the solvent gave a yellow gummy solid which was hydrogenated to the saturated acid using Pd/C as catalyst. Coupling of the resulting saturated acid to morpholine using the mixed anhydride method described in Example 17 followed by ester hydrolysis using the procedure of Example 156 gave the desired acid. Mass spectrum: (M+H) + = 328. Example 239 Boc-ACHPA-amide of 2-methylbutyl mine Using the procedure of Example 157, but replacing Boc-Sta with Boc-ACHPA and benzylamine with 2-methylbutylamine gave the .desired compound (76% yield). Mass spectrum: M = 384. Example 240 Boc-His-ACHPA-amide of 2-methylbutylamine Using the procedure of Example 164, but using the amine hydrochloride of Boc-ACHPA-amide of 2-methylbutylamine and replacing Boc-Phe-His with Boc- His-OH gave the desired compound (62% yield). Mass spectrum: (M+H) + = 522. Example 241 2(R,S)-(4-morpho1inylcarbonylmethyl)-3-(1 '-naphthyl)- propionyl-His-ACHPA-amide of 2-methylbutylamine Using the procedure of Example 164, but replacing Boc-Phe-His-OH with the product in Example 238, and using the amine hydrochloride of Example 240 gave the desired product (65% yield). Mass spectrum: (M+H) "1" = 719 Example 242 2(R,S)-(4-morpho1inylcarbonylmethyl)- 3-(4'-methoxyphenyP-propionic Acid Using the procedure described in Example 238, but replacing 1-naphthaldehyde with anisaldehyde gave the desired compound. Mass spectrum: M ** = 295. Example 243 2(R,S)-(4-morpholinylcarbonylmethyP- 3-(4'- ethoxyphenyP-propionyl-His-ACHPA-amide of 2-methylbutylamine Using the procedure of Example 164, but replacing Boc-Phe-His-OH with the product in Example 242, and using the amine hydrochloride of Example 240 gave the desired product (61% yield). Mass spectrum: (M+H) + = 699. Example 244 (3,4-cis-dihydroxypyrrolidinylcarbonyl)-Phe-methyl Ester- A suspension of L-phenylalamine methyl ester hydrochloride (10 g) in toluene (-200 ml) was heated to 100°C while phosgene gas was bubbled into the reaction mixture. After approximately 2 h the mixture became homogeneous. The bubbling of phosgene was continued for 15 more minutes keeping the temperature at -100°C. The toluene was then evaporated and the residue chased with benzene several times. The isocyanate from L-?he-OCH- was then dissolved in -100 ml of methylene chloride and 1.1 equivalent of 3-pyrroline (75% pure) was added dropwise at 0°C. After 15 min, the reaction mixture was washed with 0.5 N HCl and methylene chloride. The organic layer was washed with aqueous NaHC0 3 and dried over MgS0 4 . Evaporation of the solvent gave 3-pyrro- linylcarbonyl-Phe-methyl ester which was cis-hydroxyl- ated under the following conditions: 2.5 g of the 3-pyrrolinylcarbonyl-Phe-methyl ester was dissolved in 50 ml of THF and 1 ml of a 2.5% solution of OsO 4. in t-butanol was added, followed by 1.15 g of N-methyl- morpholine-N-oxide. After 1 h, the solvent was evaporated and the residue dissolved in 150 ml of ethyl acetate and washed with dilute N 2 S0 3 solution, satd. NaHC0 3 solution and then dried with MgS0 4 . Evaporation of the solvent gave a gummy solid which was purified by Si0 2 column chromatography (5% MeOH/ CH 2 C1 2 ) to give the desired compound (65% yield). Mass spectrum: M + = 308. Example 245 (3,4-cis-dihydroxypyrrolidinylcarbonyP-Phe-OH Using the procedure of Example 156 and replacing Boc-Sta-OEt with the compound from Example 244 gave the desired compounidd.. MMaassss ssppectrum: M = 294. Example 246 (3,4-cis-dihydroxypyrrolidinylcarbonyP- O-methyl-Tyr-methyl Ester Using the procedure described in Example 244 " and replacing L-phenylalanine methyl ester with L-O-methyl-tyrosine methyl ester gave the desired compound. Mass spectrumt.:: MM + == 333388 Example 247 ( 3 , 4-cis-dihydroxypyrrol idmylcarbonyP - O-methyl-Tyr-OH Us ing the procedure described in Example 156 and replacing Boc-Sta-OEt with the compound from Example 92 gave the desired* compound. Mass spectrum: M + = 324. Example 248 Boc-S-methyl-cys-ACHPA- mide of 2-Methylbutylamine Using the procedure described in Example 165, but replacing Boc-( α -NaphthyPAla-Ala-OH with 3oc-S- methyl-Cys-OH and using the amine hydrochloride of the compound from Example 85 gave the desired compound. Mass spectrum: (M+H) + = 502. Example 249 (3,4-cis-dihydroxypyrrolidinylcarbonyl)-Phe- S-methyl-cys-ACHPA-amide of 2-Methylbutylamine Using the procedure described in Example 165 but replacing . Boc( α -Naphthyp-Ala-Ala-OH with the compound from Example 245 and the amine hydrochloride of the compound from Example 248 gave the desired compound. Mass spectrumn:: ((MM++HH)) + == 678 Example 250 Boc-O-methyl-Ser-ACHPA-amide of 2-Methylbutylamine Using the procedure described in Example 165, but replacing Boc-( -NaphthyP-Ala-Ala-OH with Boc-O- methyl-Ser-OH and using the amine hydrochloride of the compound from Example 239 gave the desired compound. Mass spectrum: (M+H) + = 486. Example 251 (3,4-cis-dihydroxypyrrolidinylcarbonyl)- O-methyl-Tyr-O-methyl-Ser-ACHPA Amide of 2-Methylbutylamine Using the procedure described in Example 165, but replacing Boc-(α -NaphthyP-Ala-Ala-OH with the compound from Example 247 and using the amine hydro¬ chloride of the compound from Example 250 gave the desired compound. Mass spectrum: (M+H) = 682. Example 252 [ (4-Thiomorpholinyl)carbonyl3-?he Methyl Ester A suspension of L-phenylalamine methyl ester hydrochloride (6 g) in toluene (125 ml) was heated to 100°C and phosgene gas was bubbled into the reaction mixture. After approximately 1.5 h, the mixture became homogeneous. The bubbling of phosgene was continued for 10 more min. The solvent was then evaporated and the residue chased with benzene several times. The residue was then dissolved in -100 ml of methylene chloride and cooled to -0°C, and 1.1 equivalent of thiomorpholine was added dropwise. After 10 min the solution was washed with IN HCl and the organic layer was dried with MgS0 4 . Evaporation of solvent gave 5.5 g of product. Mass spectrum: M = 308. Example 253 [ (4-Sulphonylmorpholinyl)carbonyl3-Phe Meth y l Ester To 2 g of the product from Example 252 in 100 ml of methylene chloride was added 2.94 g of a meta-chloroperbenzoic acid at 0°C. After 30 min the solvent was evaporated and ether solution was washed with 10% sodium sulfite solution and then with satd. sodium bicarbonate several times. The organic layer was dried with MgS0 4 and evaporation of the solvent gave a white solid which was purified by silica gel column chromatography (20% EtOAc/80%/CH 2 Cl 2 ) to give 2.10 g (95%) of pure product. Mass spectrum: M + = 340. Example 254 [ (4-sulfonylmorpholinyl)carbonyl]-Phe-OH Using the procedure described in Example 156, but replacing Boc-Sta-OEt with the compound from " Example 253 gave the desired compound. Example 255 [ (4-sulfonylmorpholinyl)carbonyl]-Phe- O-methyl-Ser-ACHPA-amide of2-Methylbutylamine Using the procedure described in Example 165, but replacing 3oc-( α -NaphthyPAla-Ala-OH with the product from Example 254 and using the amine hydro¬ chloride of the compound from Example 250 gave the desired compound (70% yield). Mass spectrum: (M+H) + = 694. Example 256 N-(3-MethylbutyP-4-hydroxy-5-t-butyloxycarbonylamino- 6-cyclohexylhex-l-ene-2-carboxamide A solution of N-(3-methylbutyl)-2-methylpropen- amide (643 mg, 4.15 mmol) in 25 ml of dry tetrahydro¬ furan was cooled under an 2 atmosphere to -78°C and treated dropwise with 3.28 ml (8.5 mmol) of n-butyl- lithium in hexane. The resulting solution was warmed to 0°C for 20 min, recooled to -78°C and treated with 6.2 ml (6.2 mmol) of chlorotitanium triisopropoxide in hexane. After again warming to 0°C for 5 min, the dark solution was recooled to -78°C treated with a solution of N-t-butyloxycarbonylcyclohexylalininal (670 mg, 2.3 mmol) in 5 ml of tetrahydrofuran, stirred for 5 min at -78°C, warmed to 0°C for 20 min and quenched with saturated aqueous ammoniun chloride. The resulting suspension was treated with ca. 50 ml of ether, stirred until the salts became white, extracted with two 100 ml portions of ether, dried over MgS0 4 and concentrated in vacuo. The crude mixture was separated by flash column chromatography using 4:1 chloroform/ ethyl acetate to give 249 mg (26%) of the (4S,5S) product (R f .44), 292 g (31%) of the (4R,5S) product (R f .36, 3:2 chloroform/ethyl acetate) and 184 mg (20%) of a ca. 1:1 mixture of the two products. Mass spectrum: M = 410. Example 257 N-Isobuty1-4-hydroxy-5-t-butyloxycarbonylamino- 6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 256, but replacing N-(3-methylbutyl)-2-methyl-propenamide with N-isobutyl-2-methylpropenamide gave a ca. 1:1 mixture of the (4S,5S) product (R f .39) and (4R,5S) product (R f .31, 3:2 chloroform/ethyl acetate) which were separated by flash column chromatography using 3:1 chloroform/ ethyl acetate. Mass spesccttrruumm:: MM = 396 Example 258 N-Methyl-4-hydroxy-5-t-butyloxycarbσnylamino- 6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 256, but replacing N-(3-methylbutyl)-2-methyl-propenamide with N,2-dimethylpropenamide gave a c_a. 1:1 mixture of (4S,5S) product (R f .13) and (4R,5S) product (R f .08, 3:2 chloroform/ethyl acetate) in 61% yield which were partially separated by flash column chromatography using 3:2 chloroform/ethyl acetate. Mass spectrum: M + = 354. Example 259 N-(2,2-Dimethy1-3-(N, -dimethylamino) ro yl)- 4-hydroxy-5-t-butyloxycarbonylamino- 6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 256, but replacing N-(3-methylbutyl)-2-methylpropenamide with N-(2,2-dimethy1-3-(N,N-dimethylamino)propyl)-2-methy1- propenamide gave a ca. 1:1 mixture of (4S,5S) and (4R,5S) products (R f .39, 1:1 methanol/chloroform) in 77% yield which were separated from remaining starting material by preparative thin layer chromatography using 1:1 methanol/chloroform. Further separation of diastereomers was not feasible. Mass spectrum: M = 453. Example 260 N-(3-t-Butyloxycarbonylammo-2,2-dimethylpropyl)- 4-hydroxy-6-cyclohexyl-5-triphenyl- methylaminohex-l-ene-2-carboxamide A solution of N-t-butyloxycarbonyl-N'-2-methyl- propenoyl-2,2-dimethyl-l,3-propanediamine (270 mg, 1.0 mmol) in 10 ml of dry tetrahydrofuran was cooled under a N 2 atmosphere to -78°C, treated dropwise with 1.68 ml (3.0 mmol) of n-butyllithium in hexane, stirred at -78°C for 5 min, warmed to 0°C for 30 min, recooled to -78°C and treated with 266 mg (0.67 mmol) of N-(triphenyl- methypcyclohexylalaninal in 3 ml of tetrahydrofuran. After stirring at -78°C for 10 min, the resulting solution was treated with acrueous NH 4.C1, extracted with 40 ml of ether, washed with 10 ml of saturated aqueous NaCl, dried over MgS0 4 , and concentrated in vacuo. Pure product (51% yield), as a mixture of (4S,5S) and (4R,5S) diastereomers was obtained after flash column chromatography using 1.8:1 hexane/ethyl acetate (R f .51, 1:1 hexane/ethyl acetate). Mass spectrum: (M+l) + = 668. Example 261 5-t-3utyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-(N- (3-methylbutyl)carboxamido)hex-l-ene-1,2-oxide A solution of the resultant (4S,5S) diastereomer of Example 256 (206 mg, 0.50 mmol) in 8 ml of dichloromethane was treated with 217 mg (1.0 mmol) of 3-chloroperoxybenzoic acid and allowed to stand at room temperature. After 18 h, the solution was diluted with 5 ml of ether, treated with 10% aqueous Na 2 S 2 0 3 , stirred vigorously for 1.5 h, extracted with 25 ml of ether, washed sequentially with 3N NaOH and saturated brine, dried over MgS0 4 and concentrated m vacuo to give a 1.1:1 mixture of (2R) (R f .49) and (2S) (R f .40, 3:2 chloroform/ethyl acetate) diastereomers, respectively, in 100% yield. The diastereomeric products were separated by flash column chromatography " using 5.5:1 chloroform/ethyl acetate. For each isomer, mass spectrum: M + = 426 Example 262 5-t-Butyloxycarbonylamino-6-cyclohexyl-4-hydroχy- 2-(N-isobutylcarboxamido)hex-l-ene-l,2-oxide Using the procedure of Example 261, but replacing the compound from Example 256 with the resultant (4S,5S) diastereomer from Example 257 gave, after flash column chromatography using 5:1 chloroform/ethyl acetate, the desired (2R) (R .44) and (2S) (R f .37, 3:2 chloroform/ethyl acetate) diastereomeric products in 53% and 47% yields, rreessppectively. For each isomer, mass spectrum: M = 412. Example 263 (4S,5S)-N-(3-Methylbutyl)-5-t-butyloxycarbonylamino- 6-cyclohexylhexane-l,4-diol-2-carboxamide Ammonia (ca.. 10 ml) was condensed into a flask containing 10 ml of dry tetrahydrofuran precooled to -78°C. The resulting mixture was treated with <ca. 30 mg of lithium metal, stirred at -78°C for 10 min, treated with a solution of the mixture of epoxides produced in Example 261 in 1 ml of tetrahydrofuran, stirred at -78°C for 6 min and cautiously poured into a rapidly stirred mixture of ether and saturated aqueous NH 4 C1. The organic layer was separated, dried over MgS0 4 and reduced iτ_ vacuo. Separation by flash column chromatography using 1.8:1 chloroform/ethyl acetate followed by 13:1 chloroform/methanol gave a 66% yield (78% based on recovered starting material) of the desired compound as an inseparable 1.5:1 mixture of diastereomers (R f .04, 3:2 chloroform/ethyl acetate). Mass spectrum: (M+l) + = 429. Example 264 (4S,5S)-N-(3-Methylbutyl)-l-acetoxy- 4-hydroxy-5-t-butyloxycarbonylamino- 6-cyclohexylhexane-2-carboxamide A solution of the resultant compound of Example 263 (40.2 mg, 0.094 mmol) in 0.3 ml of dry dichloromethane was treated sequentially with 14.5 uL (0.10 mmol) of triethylamine and 9.8 uL (0.10 mmol) of acetyl chloride. After being allowed to stir overnight, the mixture was partitioned between dichloromethane and water, dried over a 2 S0 4 and purified by flash column chromatography using 24:1 chloroform/ methanol as eluent to give a quantitative yield of the desired compound as a mixture of diastereomers (Rf .45, 12:1 chloroform/methanol) , Examp,e 265 (2R > 4S,5S)-N-Isobutyl-l-azido-5-t-butyloxycarbonylamino- 6-cyclohexylhexane-2,4-diol-2-carboxamide A solution of 51.0 mg (0.124 mmol) of the resultant (2R) diastereomer from Example 261, 24 mg (0.37 mmol) of sodium azide and 15 mg (0.28 mmol) of ammonium chloride in 7 ml of methanol was heated at reflux for 18 h. The resulting mixture was partitioned between chloroform and water, dried over Na„ 2SO4. and reduced to give a 98% yield of the desired compound which was homogenous by tic (R- .54, 3:2 chloroform/ ethyl acetate). Mass spectrum: (M+l) = 456. Example 266 (2S,3S,5S)-N-Isobutyl-2-t-butyloxycarbonylammo- l-cyclohexyl-7-methyloctane-3,5-diol-5-carboxamide A solution of 21,4 mg (0.052 mmol) of the resultant (2R) diastereomer of Example 261 in 1 ml of dry tetrahydrofuran was cooled under a N 2 atmosphere to 0°C and treated with 0.13 ml * (0.26 mmol) of isopropylmagnesium chloride in ether. After 45 min, the mixture was treated with saturated aqueous NH 4 C1, extracted with ether and dried over MgS0 4 ). Separation by flash column chromatography using 3:1 hexane/ethyl acetate gave a 25% yield (57% based on" recovered starting material) of the desired compound ( ^ .30, 6:1 chloroform/ ethyl acetate). Mass spectrum: (M+l) + = 457. Example 267 (4S,5S)-N-(3-Methylbutyl)-5-t-butyloxycarbonylamino- 6-cyclohexylhexane-l,2,4-triol-2-carboxamide A solution of 135 mg (0.33 mmol) of the (4S,5S) diastereomer from Example 256 in 4 ml of tetrahydrofuran was treated sequentially with 170 ml (0.017 mmol) of osmium tetroxide in t-butanol and ca. 100 mg (0.7 mmol) of 4_-methylmorpholine-N-oxide. After stirring for 24 h, the solution was diluted with 50 ml of ether, washed sequentially with five 4 ml portions of 10% Na 2 S 2 0 3 , 4 ml of 1M HCl, 4 ml of H 2 0 and 4 ml of saturated aqueous NaHC0 3 and dried over MgS0 4 . Separation by flash column chromatography using 19:1 chloroform/ methanol gave an 88% yield of the desired compound as a 1:1 mixture of diastereomers (R .35, 12:1 chloroform/ methanol). Mass spectrum: M = 444. Example 268 (4S,5S)-N-Isobuty1-5-t-butyloxycarbonyl mino- 6-cyclohexylhex-l-ene-3,4-diol-2-σarboxamide A solution of 173 mg (0.44 mmol) of the (4S,5S) diastereomer from Example 257 and 68 mg (0.52 mmol) of selenious acid in 4 ml of dioxane was heated at 70°C for 16 h and 95°C for 4 h. After cooling, filtration through Celite and separation by flash column chromatography using 7:3 chloroform/ethyl acetate gave a 50% yield of the desired compound (R f .25, 7:3 chloro¬ form/ethyl acetate) as a 1:1 mixture of diastereomers. Mass spectrum: M + = 412. Example 269 (4S,5S)-N-(3-Methylbutyl)-5-amino-4-hydroxy- 6-cyclohexylhex-l-ene-2-carboxamide hydrochloride The (4S,5S) diastereomer from Example 256 (31.5 mg, 0.077 mmol) was treated with 0.5 ml of a 4 M " solution of HCl in dioxane and allowed to stand at ambient temperature for 1 h. After removal of the solvent in vacuo, the residue was treated twice with 0.5 ml of anhydrous ether followed each time by removal of the solvent m vacuo. The crude amine hydrochloride was used without further purification. Example 270 (4S,5S)-N-Isobutyl-5-amino-4-hydroxy- 6-cyclohexylhex-l-ene-2-carboxamide hydrochlo ide Using the procedure of Example 269 with the resultant (4S,5S) diastereomer of Example 257 gave the desired compound. Example 271 (4S,5S)-N-Methyl-5-amino-4-hydroxy- 6-cyclohexylhex-l-ene-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant (4S,5S) diastereomer of Example 258 gave the desired compound. Example 272 N-(2 ,2-Dimethy1-3-(N, -dimethylamino) ropy1)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene- 2-carboxamide dihydrochloride A solution of 45 mg (0.1 mmol) of the resultant compound of Example 259 in ___.. 0.1 ml of absolute ethanol was treated with 0.6 ml of 4 M HCl in dioxane and allowed to stand at ambient temperature for 1.5 h. After removal of the solvent in vacuo, the residue was treated twice with 0.5 ml of anhydrous ether followed each time by removal of the solvent m vacuo. The crude diamine dihydrochloride was used without further purification. Example 273 N-(3-t-Butyloxycarbony1amino-2,3-dimethylpropy1)- 5-ammo-4-hydroxy-6-cyclohexylhex-l-ene- 2-carboxamide acetic acid salt A solution of 80.3 mg (0.12 mmol) of the resultant compound of Example 260 in c_a. 1.5 ml of 1:1 acetic acid/ethanol was treated with 5 drops of H 2 0 and allowed to stir at ambient temperature for 9 h. After concentration in vacuo, the residue was treated twice with benzene and once with ether followed each time by removal of the solvent in vacuo. The resulting oil was digested twice with hexane, followed each time by decantation. Removal of the last traces of solvent gave the desired compound as a mixture of diastereomers which was used without further purification. Example 274 (4S,5S)-N-(3-Methylbuty1)-l-acetoxy-5-amino-4-hydroxy- 6-cyclohexylhexane-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant compound of Example 264 gave the desired compound. Example 275 (2R,4S,5S)-N-Isobutyl-5-amino-l-azido- 6-cyclohexylhexan-2,4-diol-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant compound of Example 265 gave the desired compound. Example 276 (2S,3S,5S)-N-Isobutyl-2-amino-l-cyclohexyl- 7-methyloctan-3,5-diol-5-carboxamide hydrochloride Using the procedure of Example 269 with the resultant compound of Example 266 gave the desired compound. Example 277 (2S,4S,5S)-N-Isobutyl-4-amino-l-chloro- 6-cyclohexylhexane-2,4-diol-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant (2R) diastereomer of Example 262 gave the desired compound. Example 278 (4S,5S)-N-(3-Methylbutyl)-5-amino-6-cyclohexylhexane- 1,2,4-triol-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant compound of Example 267 gave the desired compound as a mixture of diastereomers. Example 279 (4S,5S)-N-Isobutyl-5-ammo-6-cyclohexylhex-l-ene- 3, -diol-2-carboxamide hydrochloride Using the procedure of Example 269 with the resultant compound of Example 268 gave the desired compound as a mixture of diastereomers. Example 280 Boc-Phe-Ala amide of (4S,5S)-N-(3-methylbutyP- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide A solution of 39 mg (0.115 mmol) of Boc-Phe-Ala-OH and 13 uL (0,12 mmol) of 4-methyl- morpholine in 0.5 ml of dichloromethane and 0.1 ml of dimethylformamide was cooled to -15°C and treated with 15 uL (0.12 mmol) of isobutyl chloroformate. After being allowed to stir for 5 min, the solution was treated with a mixture of 0.077 mmol of the resultant compound of Example 269 and 8.4 uL (0.077 mmol) of 4-methylmorpholine in 0.6 ml of 2:1 dimethylformamide/ dichloromethane, and allowed to stir at -15 - 0°C for .5 h and at ambient temperature for 2 h. After dilution with ca_. 10 ml of ethyl acetate; the solution was washed successively with 1 ml of 1 M HCl, 1 ml of H 2 0, 1 ml of saturated ' aqueous NaHC0 3 and 1 ml of H 2 0; dried over MgS0 4 and concentrated m vacuo. Separation by flash column chromatography using 2.5% methanol in chloroform gave 27 mg (56%) of the desired compound which was recrystallized from chloroform/hexane. Mass spectrum: (M+H) + = 629. Example 281 3oc-Phe-Ala amide of (4S,5S)-5-amino-4-hydroxy- 6-cyclohexyl-2-(N-(3-methylbutyl)carbox- amidohex-l-ene-1,2-oxide A solution of 11 mg (0.018 mmol) of the resultant compound of Example 280 and 13 mg (0.11 mmol) of 3-chloroperoxybenzoic acid in 0.5 ml of dichloro¬ methane was allowed to stir at ambient temperature overnight. The resulting solution was treated with 0.5 ml of 10% Na 2 S 2 0 3 , allowed to stir for 1 h, diluted with 3 ml of ethyl acetate, extracted with aqueous NaHC0 3 , dried over MgS0 4 and concentrated in vacuo. Purification by flash column chromatography using 1-2% methanol in chloroform gave 7.6 mg (67%) of the desired compound as a ca. 1:1 mixture of diastereomers (R f .38, .41, 7.5% methanol in chloroform) . - Mass spectrum: (M+H) = 645. Example 282 Boc-Phe-His amide of (4S,5S)-N-( -methylbutyl)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide A solution of 52 mg (0.13 mmol) of Boc-Phe- His-OH and 52 mg (0.39 mmol) of 1-hydroxybenzotriazole monohydrate in 0.6 ml of dimethylformamide was cooled to -23°C, treated with 25 mg (0.13 mmol) of l-ethyl-3-(di- methylaminopropyPcarbodiimide hydrochloride, and allowed to stir for 1 h. A solution of 0.13 mmol of the resultant compound of Example 269 and 29 uL (0.26 mmol) of 4-methylmorpholine in 0.6 ml of dimethylformamide was subsequently added, and the resulting solution was stirred at -23°C for 3 h and at ambient temperature for 16 h. After dilution with 10 ml of ethyl acetate, the solution was washed sequentially with 1 ml of saturated aqueous NaHC0 3 and 1 ml of H 2 0, dried over MgS0 4 , and concentrated m vacuo. Purification by flash column chromatography using 10% methanol in chloroform gave 49 mg (55%) of the desired compound (R f .20, 10%" methanol in chloroform) which was recrystallized from tetrahydrofuran/hexane, m.p. 178-180°C (dec). Mass spectrum: M + = 694 Example 283 Boc-Phe-His amide of N-(2,2-dimethy1- 3-(N,N-dimethylamino)propyl)-5-amino- 4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide A solution of 3.09 g (6.83 mmol) of the resultant compound of Example 272, 2.75 g (6.83 mmol) of Boc-Phe-His-OH, and 3.27 g (24.2 mmol) of 1-hydroxy- benzotriazole in 20 ml of dimethylformamide was treated with 750 uL (6.83 mmol) of 4-methylmorpholine, cooled to -23°C, and treated with 1.31 g (6.83 mmol) of 1-ethyl- 3-(dimethylaminopropyPcarbodiimide hydrocholo ide. After being allowed to stir at -23°C for c_a. 2 h and at ambient temperature for 14 h, the solution was diluted with ethyl acetate, washed sequentially with aqueous NaHC0 3 and H 2 0, dried (MgS0 4 ) and concentrated in vacuo■ Separation by flash column chromatography using 2% methanol/2% isopropylamine in chloroform gave a 58% yield of the desired compound (R f .10, 2% methanol/2% isopropylamine in chloroform) as a mixture of stereoisomers. Mass spectrum: (M+H) = 738. Example 284 Boc-Phe-His amide of (4S,5S)-N-(3-methylbutyP- l-acetoxy-5-amino-4-hydroxy- 6-cyclohexylhexane-2-carboxamide Using the procedure of Example 282 with the resultant compound of Example 274 gave, after purification by flash column chromatography using 7.5-10% methanol in chloroform, a 67% yield of the desired compound (R- .26, 10% methanol in chloroform) as a mixture of diastereomers. Mass spectrum: (M+H) = 755. Example 285 Boc-Phe-His amide of (4S,5S)-N-(3-methylbutvP- 5-amino-6-cyclohexylhexan-l_ 4-diol-2-carboxamide A solution of 40 mg (0.05 mmol) of the resultant compound of Example 284 in 0.3 ml of dioxane and 0.15 ml of H 2 0 was treated with 7 mg of LiOH " H 2 0 and allowed to stir at ambient temperature for 3 h. The resulting solution was partitioned between ethyl acetate and H 2 0, dried over MgS0 4 , and concentrated in vacuo. Separation by flash column chromatography using 15% methanol in chloroform gave the desired compound as a mixture of diastereomers. Mass spectrum: (M+H) + = 713. Example 286 Boc-Phe-His Amide of (2R,4S,5S)-N-isobutyl-5-ammo- l-azido-6-cyclohexylhexane-2,4-diol-2-carboxamide Using the procedure of Example 283 with the resultant compound of Example 275 gave, after purification by flash column chromatography using 5% methanol in chloroform, a 72% yield of the desired compound (R f .23, 7.5% methanol in chloroform). Mass spectrum: (M+H) + = 740.. Example 287 (5N)-Boc-Phe-His amide of (2R,3S, 5S)-N-isobutyl- 6-cyclohexyl-l,5-diaminohexane-2,4-diol-2-carboxamide A solution of 8.2 mg (0.011 mmol) of the resultant compound of Example 286, 2 uL ^ (0.035 mmol) of glacial acetic acid, and c_a. 5 mg of 10% palladium on carbon in 0.5 ml of methanol was stirred overnight under a H 2 atmosphere. After dilution with chloroform, the mixture was filtered through Celite, concentrated in vacuo, filtered through a plug of basic alumina using 1:1 methanol/ethyl acetate as an eluent, concentrated, dissolved in chloroform, filtered, and concentrated to give 7.9 mg (100%) of the desired compound as a white solid. Mass spectrum: ((MM++HH)) ++ == 77114 Example 288 Boc-Phe-His amide of (2S,3S,5S)-N-isobutyl-2-amino- l-cyclohexyl-7-methyloctane-3,5-diol-5-carboxamide Using the procedure of Example 283 with the resultant compound of Example 276 gave, after purification by flash column chromatography using 6% methanol in chloroform, an 85% yield of the desired compound (R f .16; 7.5% methanol in chloroform). Mass spectrum: (M+H) + = 741. Example 289 Boc-Phe-His amide of (2S,4S,5S)-N-isobutyl-4-ammo- l-chloro-6-cyclohexylhexane-2,4-diol-2-carboxamide Using the procedure of Example 283 with the resultant compound of Example ' 277 gave, after purification by flash column chromatography using 7.5% methanol in chloroform, a 68% yield of the desired compound (R f .24, 7.5% methanol in chloroform). Mass spectrum: (M+H) + = 733, 735. Example 290 Boc-Phe-Ala amide of (4S,5S)-N-(3-methylbutyl)- 5-amino-6-cyclohexylhexan-l,2,4-triol-2-carboxamide Using the procedure of Example 280 with the resultant compound of Example 278, gave, after purification by flash column chromatography using 5% methanol in chloroform, a 38% yield of the desired compound (R f .27, 7.5% methanol in chloroform) as a 1:1 mixture of diastereomers. Mass spectrum: (M+H) + = 663. Example 291 Boc-Phe-His amide of (4S,5S)-N-isobutyl- 5-amino-6-cyclohexylhex-l-ene-3,4-diol-2-carboxamide Using the procedure of Example 283 with the resultant compound of Example 279 gave, after purification by flash column chromatography using 7.5-10% methanol in chloroform, the desired compound as a 1:1 mixture of diastereomers. Mass spectrum: (M-H)- = 695. - Example 292 Boc-His amide of (4S,5S)-N-(3-methylbutvP- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 282 but replacing Boc-Phe-His-OH with Boc-His-OH gave, after purification by flash column chromatography using 7.5% methanol in chloroform, a 76% yield of the desired compound (R^ .21, 7.5% methanol in chloroform), m.p. 97-99-C. Mass spectrum: (M+H) + = 548. Example 293 His amide of (4S,5S)-N-(3-methylbutyP- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene- 2-carboxamide dihydrochloride Using the procedure of Example 272 with the resultant compound of Example 292 gave the desired compound. Example 294 Boc-6-aminohexanoic acid A mixture of 3.0 g (0.02 mol) of 6-amino- hexanoic acid, 5.04 g (0.02 mol) of di-t-butyldicar- bonate and 3.84 g (0.05 mol) of NaHC0 3 in 160 ml of 1:1 H_0/tetrahydrofuran was stirred vigorously for 24 h. After concentration of the solvent, the mixture was acidified with HCl, saturated with NaCl, extracted with ethyl acetate, dried over MgS0 4 and concentrated in vacuo to give the desired product (R f 0.48, 9:1 chloroform/methanol) . Example 295 Boc-6-aminohexanoyl-Phe benzyl ester A solution of 1.50 g (6.5 mmol) of the resultant compound of Example 294, 2.77 g (6.5 mmol) of phenylalanine benzyl ester p-toluenesulfonate salt, 0.87 g (6.5 mmol) of 1-hydroxybenzotriazole hydrate, 1.19 ml (8.4 mmol) of triethylamine and 1.74 g (8.4 mmol) of dicyclohexylcarbodiimide in 150 ml of tetra¬ hydrofuran was allowed to stir at ambient temperature " for 18 h. After concentration iri vacuo, the residue was taken up in 300 ml of ethyl acetate, filtered, washed consecutively with 1 M HCl, H 2 0, saturated NaHC0 3 , H 2 0 and saturated NaCl; dried over MgS0 4 and concentrated. Purification by flash column chromatog¬ raphy using 4:1 chloroform/ethyl acetate gave 2.35 g (77%) of the desired compound (R f 0.21, 4:1 chloroform/ethvl acetate) . Example 296 Boc-6-aminohexanoyl-Phe-OH A mixture of 0.5 g (1.07 mmol) of the resultant compound of Example 295 and 30 mg of 10% palladium on carbon in 50 ml of methanol was stirred under an H„ atmosphere for 3.5 h. After filtration through Celite, concentration in vacuo gave the desired compound. Example 297 Boc-6-aminohexanoyl-Phe-His amide of (4S,5S)-N-(3-methylbutyl)-5-amino-4-hydroxy- 6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 283 with the resultant compound of Example 293 but replacing Boc-Phe- His-OH with Boc-6-aminohexanoyl-Phe-OH gave, after purification by flash column chromatography using 7.5% methanol in chloroform, the desired compound (R tf .20, 10% methanol m chloroform) . Mass spectrum: (M+H) = 808. Example 298 6-Aminohexanoyl-Phe-His amide of (4S,5S)-N-(3-methylbutyl)-5-amino-4-hydroxy- 6-cyclohexylhex-l-ene-2-carboxamide bis trifluoroacetate A solution of the resultant compound of Example 297 (17 mg, 0.021 mmol) in 0.2 ml of trifluoroacetic acid was allowed to stand at ambient temperature for 40 min. After removal of the solvent .in vacuo, and the residue was treated three times with 0.5 ml of ether and concentrated in vacuo to give the desired compound as a ~ white solid. Mass spectrum: (M+H) = 708. Example 299 t-Butylacetyl-Phe-His amide of N-(3-t-butyloxycarbonylamino-2,2-dimethylpropyl)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 283 with the resultant compound of Example 273 but replacing Boc-Phe- His-OH with t-butylacetyl-Phe-His-OH gave, after purification by flash column chromatography using 7.5% methanol in chloroform, a 32% yield of the desired compound as a mixture of diastereomers (R f .09, .11, 7.5% methanol in chloroform). Mass spectrum: (M+H) = 808. Example 300 (5N)-t-Butylacetyl-Phe-His amide of N-(3-ammo-2,2-dimethyloropyl)-5-amino- 6-cyclohexylhex-l-en-4-ol-2-carboxamide Using the procedure of Example 272 with the resultant compound of Example 299 gave a white solid. Purification and neutralization by flash column chromatography using .7.5-10% methanol/2% isopropyl¬ amine in chloroform gave a 38% yield of the desired compound (R f .29, 10% methanol/2% isopropylamine in chloroform). Mass spectrum: (M+H) + = 708. Example 301 (4S,5S,8R,10R,llS)-N-Isobutyl-6-aza- ll-(t-butyloxycarbonylamino)-5-(cyclohexylmethyl)- 4,10-dihydroxy-8-isobutyl-7-oxo-12- phenyldodec-l-ene-2-carboxamide Using the procedure of Evans, et aP (J. Orq. Chem. 1985, 5_0, 4615) with the resultant compound of Example 270 and (3R,5R,1 'S)-5-(l-(t-butyloxycarbonyl- amino)-2-phenylethyl)-3-isobutyldihydrofuran-2-(3H)-one (D.J. Kempf, J. Orq. Chem. 1986, __1 , 3921) gave the desired compound after purification by column chromatog¬ raphy using 3:2 ethyl acetate: exane. Mass spectrum: " (M+H) + = 658. Example 302 (4S,5S,8R,10S,llS)-N-Isobutyl-6-aza- ll-(t-butyloxycarbonylamino)-5-(cyclohexylmethyl)- 4, 10-dihydroxy-7-oxo-8-(4-pentenyP- 12-phenyl-dodec-l-ene-2-carboxamide Using the procedure of Evans, et aP (J. Orq. Chem, 1985, 5_0, 4615) with the resultant compound of Example 270 and (3R,5S,1 'S)-5-(l-(t-butyloxycarbonyl- amino)-2-phenylethyl)-3-(4-pentenyl)dihydrofuran- 2-(3H)-one (D.J. Kempf, J. Orq. Chem. 1986, 5_1, 3921) gave the desired compound after purification by MPLC using 3:2 ethyl acetate:hexane. Mass spectrum: (M+H) = 670. Example 303 N-Methyl-N-(2-(N,N-dimethylamino)ethyl)carba oyl- (0-methyl)tyrosine methyl ester A solution of 0.5 g (2.1 mmol) of the resultant compound of Example 136 in 50 ml of dichloromethane was cooled to 0°C and treated with 0.3 ml (2.3 mmol) of N,N,N'-trimethylethylenediamine. After being allowed to stir for 16 h, the solution was concentrated and the desired compound was isolated by flash column chroma¬ tography using 1% methanol/2% isopropylamine in chloroform. Example 304 N-Methyl-N-(2-(N,N-dimethylamino)ethyl)carba oyl- (O-methyl)tyrosine lithium salt A solution of the resultant compound of Example 303 in dioxane was cooled to 0°C, treated with 1.05 equiv. of aqueous lithium hydroxide (0.5 M) and stirred for 1.5 h. The resulting solution was concentrated in vacuo to give the desired compound as a white solid. Example 305 N-Methyl-N-(2-(N,N-dimethylamino)ethyl)carbamoyl- (O- ethyl)Tyr-His amide of (4S,5S)-N-(3-methylbutyl)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 283 but replacing Boc-Phe-His-OH with the resultant compound of Example 304 and replacing the resultant compound of Example 272 with the resultant compound of Example 293 gave the desired compound. Example 306 5-Carbomethoxypentanoyl-(0-methyl)Tyr benzyl ester Using the procedure of Example 280 but replacing Boc-Phe-Ala-OH with adipic acid monomethyl ester and replacing the resultant compound of Example 269 with (O-methyl)tyrosine benzyl ester hydrochloride gave the desired compound. Example 307 5-Carbomethoxypentanoyl-(O-methyl)Tyr-OH A solution of the resultant compound of Example 306 and 20% palladium on carbon in methanol was shaken under an H 2 atmosphere. After filtration, concentra¬ tion of the solution in vacuo gave the desired compound. Example 308 5-Carbomethoxypentanoyl-(O-methyl)Tyr-Leu benzyl ester Using the procedure of Example 280 but replacing Boc-Phe-Ala-OH with the resultant compound of Example 307 and replacing the resultant compound of Example 269 with leucme benzyl ester p-toluenesulfonate salt gave, after purification by flash column chromatog¬ raphy using 20% ethyl acetate in chloroform, the desired compound in 64% yield. Example 309 5-Carbomethoxypentanoyl-(O-methyl)Tyr-Leu-OH A solution of the resultant compound of Example 308 and 20% palladium on carbon in methanol was shaken under an H 2 atmosphere. After filtration, concentra¬ tion of the ' solution in vacuo gave the desired compound " in 97% yield. Example 310 5-Carbomethoxypentanoyl-(O-methyl)Tyr-Leu amide of N-(2,2-dimethyl-3-(N,N-dimethylamino)propyl)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide Using the procedure of Example 280 but replacing Boc-Phe-Ala-OH with the resultant compound of Example 309 and replacing the resultant compound of Example 269 with the resultant compound of Example 272 gave, after purification by flash column chromatography using 1.25% methanol/1% isopropylamine/chloroform, the desired compound in 57% yield (R f 0.38 (2.5% methanol/ 2% isopropylamine/chloroform) ) . Example 311 5-Carboxypentanoyl-(O-methyl)Tyr-Leu amide of N-(2,2-dimethyl-3-(N,N-dimethylamino) ropy1)- 5-amino-4-hydroxy-6-cyclohexylhex-l-ene-2-carboxamide A solution of the resultant compound of Example 310 (319 mg, 0.41 mmol) in 10 ml of tetrahydrofuran was treated with a solution of 85 mg (2.0 mmol) of lithium hydroxide hydrate in 10 ml of H 2 0 and allowed to stir at ambient temperature for 1 h. The resulting solution was neutralized to pH 7 with 1 M HCl, extracted with three 100 ml portions of chloroform, dried, and concentrated to give 268 mg (86%) of the desired compound as a white solid. Mass spectrum: (M+H) = 772. Example 312 4-t-Butyloxycarbonylamino-2,2-difluoro- 3-hydroxy-5-cyclohexylpentanoic acidethyl ester. To a solution of 8.0 g of Boc-cyclohexyl¬ alaninal in 125 ml of tetrahydrofuran at 10°C was added 10 ml of ethyl bromodifluoroacetate. The reaction flask was immersed in a sonicating bath. To this solution was added portionwise 6.18 g of zinc dust. After 30 min of sonication TLC check showed reaction was essentially- complete. The reaction mixture was filtered through a tightly packed pad of Celite and the filtrate was concentrated. The residual oil was dissolved in methylene chloride and washed with 0.5 M potassium bisulfate. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated. Purification by silica gel column (20% ethyl acetate/80% hexane) provided 4.5 g of 3R isomer and 4.0 g of 3S isomer. Mass spectrum: M = 379. Example 313 4(S)-t-butyloxycarbonylamino-2,2-difluoro- 3R-hydroxy-5-cyclohexylpentanoic acid. Using the procedure of Example 156, but replacing Boc-Sta-OEt with the product from Example 312 gave the desired product. Mass spectrum: M = 351. Example 314 4S-t-butyloxycarbonylamino-2,2-difluro- 3R-hydroxy-5-cyclohexylpentanoic acid amide of 2-methylbutyl mine. Using the procedure of Example 157, but replacing Boc-Sta-OH with the product from Example 313 • and replacing benzyl amine with 2-methylbutylamine gave the desired product (75% yield). Mass spectrum: M + = 420. Example 315 Boc-Phe-His-4S-amir.o-2,2-difluorσ- 3R-hydroxy-5-cyclohexylpentanoic acid amide of 2-methylbutylamine. Using the procedure of Example 164, but using the amine hydrochloride of the product in Example 314 gave the desired product (47% yield). Mass spectrum: (M+H) + = 705. The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include but are not limited to the following: acetate, adipate, alginate," aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, heptonate, glycerophosphate, hemisulfate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, oxalate, 2-naphthalenesulfonate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, and undecanoate. Also, the basic nitrogen-containing groups can be quaternized with such agents as loweralkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides, and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl. , and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. Water or oil-soluble or dispersible products are thereby obtained. The novel compounds of the present invention possess an excellent degree of activity and specificity in treating renin-associated hypertension in a host. The ability of the compounds of the invention to inhibit human renal renin can be demonstrated .in vitro by reacting a selected compound at varied concentrations with human renal renin, free from acid proteolytic activity, and with human renin substrate (angio- tensinogen) at 37°C and pH 6.0. At the end of the incubation, the amount of angiotensin I formed is measured by radioimmunoassay and the molar concentration required to cause 50% inhibition, expressed as the ICo- n O, is calculated. Total daily dose administered to a host in single or divided doses may be in amounts, for example, from 0.001 to 10 mg/kg body weight daily and more " usually 0.01 to 1 mg. Dosage unit compositions may contain such amounts of sub ultiples thereof to make up the daily dose. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, and the severity of the particular disease undergoing therapy. The compounds of the present invention may be administered orally, parenterally, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers, .adjuvants, and vehicles as desired. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection, or infusion techniques. Injectable preparation, for example, sterile injectable aqueous or oleagenous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol . Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be " employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable nonirritating excipient such as cocoa butter and polyethylene glycols which are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug. Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, ' and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents. The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims.

Claims: WHAT IS CLAIMED IS: 1. Compounds of the formula wherein A is hydrogen; loweralkyl; arylalkyl; OR 2Q or SR 2Q wherein R 2Q is hydrogen, loweralkyl or aminoalkyl; NR l R 22 wherein R 21 and R 22 are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; wherein B is NH, alkylamino, S, 0, CH 2 , NHCH 2 or CHOH and R 23 is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxy- alkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl) (alkyl)amino, [(dialkyl¬ amino)alkyl] (alkyl) mino, (dihydroxyalkyl) (alkyl) mino, carboxyalkyl, aminoalkyl, N-protected aminoalkyl, alkyl- aminoalkyl, alkσxycarbonylalkyl, (N-protected) (alkyl)- aminoalkyl, dialkylaminoalkyl, (heterocyclic)alkyl or a ' substituted or unsubstituted heterocyclic; W is C=0 or CHOH; U is CH 2 or N 2 , provided that when W is CHOH then U is CH 2 ; R, is loweralkyl, cycloalkyl ethyl, benzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)methyl, 4-hydroxy- benzyl, _ , _ -dimethylbenzyl, 1- enzyloxyethyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R is phenoxy, thiophenoxy or anilino, B is CH 2 or CHOH or A is hydrogen; R 3 is loweralkyl, loweralkenyl, [ (alkoxy)alkoxy]loweralkyl, (thioalkoxy)alkyl, benzyl or heterocyclic ring substituted methyl; R 4 is FL R< Rr R 1 1 O wherein R_ is hydrogen or loweralkyl; R g is loweralkyl, cycloalkylmethyl, benzyl, or CH,,R 24 , where R 24 is selected from l,3-dioxan-2-yl; l,3-dioxolan-2-yl, l,3-dithiolan-2-yl or 1,3-dithian- 2-yl; R ? , R~ and R g are hydrogen or loweralkyl and may be the same or different; V is NH, 0, S, SO, S0 2 , or CH 2 ; 1Q is loweralkyl, cycloalkyl, cycloalkyl- alkyl, aryl, arylalkyl or an N-protecting group, or V and - 0 taken together are N 3 ; with the proviso that R 1Q may be an N-protecting group only when V is NH; 13 is CHOH or CO; R 14 is CH 2 , CF 2 or CF with the proviso that when R- 3 is CO, R. 4 is CF 2 ; R 15 is CH 2 , CHR 25 wherein 25 is loweralkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or R. 4 and R, 5 taken together can be with the proviso that when R 14 is CF 2 , R ιg is CH2; M is 0, S, SO, S02, NR26. wherein R2-6- is hydrogen or loweralkyl, N 27 S0 2 or NR 2? CO wherein R 27 is hydrogen or loweralkyl, or M and 1Q taken together are N 3 ; R lg is CH 2 , CF 2 or CH R 45 where R 45 is loweralkyl, hydroxy, hydroxyalkyl, alkoxy, allyl, alkaryloxy or thioalkyl R- 7 is hydrogen or loweralkyl; R, g is loweralkyl or lipophilic or ' aromatic amino acid side chains; P is hydrogen, loweralkyl or -CH 2 OR 2 g, wherein R 2g is hydrogen, loweralkyl or alkaryl; R is hydrogen or hydroxy; n is 0 or 1; when n is O, T is alkylidene or alkylidene oxide; when n is 1, S is hydrogen or hydroxy and T is loweralkyl, hydroxyalkyl, aminoalkyl, haloalkyl, or azidoalkyl; R ιg is hydrogen or loweralkyl; R 12 is hydrogen, loweralkyl, alkyl- cycloalkyl, arylalkyl, aminoalkyl, dialkylaminoalkyl; and pharmaceutically acceptable salts thereof. 2. A compound according to Claim 1 wherein R. and R, is 1- or 2-naphthylmethyl, benzyl or 4-methoxybenzyl; R 3 is loweralkyl, imidazol-4-yl- methyl, pyrazolylmethyl, or thiomethoxymethyl; 5 , ?/ g and R Q are hydrogen; R g is isobutyl or cyclohexylmethyl; V is 0, S, SO 2 , CH 2 or NH; and R 10 is loweralkyl or cycloalkyl. 3. A compound according to Claim 1 wherein R. and R. is 1- or 2-naphthylmethyl , benzyl or 4-methoxybenzyl; R 3 is loweralkyl, imidazol-4-yl- methyl, pyrazolylmethyl, or thiomethoxymethyl; R_ is hydrogen; R g is isobutyl or cyclohexylmethyl; - 3 is- CHOH or C=O; R χ4 is CF 2 or CH 2 ; R is CH 2 ; M is S, SO 2 or NHC=0; and R 1Q is loweralkyl or cycloalkyl. 4. A compound according to Claim 1 wherein R. R 6 R 17 and R χ is 1- or 2-naphthylmethyl, benzyl or 4-methoxybenzyl; R g is loweralkyl, imidazol-4-yl- methyl, pyrazolylmethyl, or thiomethoxymethyl; Rg, R 17 is hydrogen; R. g is CH 2 ; R g is isobutyl, cyclohexylmethyl or CH 2 R 24 , where 24 is l,3-dithiolan-2-yl; P is hydrogen or hydroxymethyl; and R 18 is loweralkyl. 5. A compound according to Claim 1 wherein R 4 and R, is 1- or 2-naphthylmethyl, benzyl or 4-methoxybenzyl; R 3 is loweralkyl, imidazol-4-yl- methyP pyrazolylmethyl, or thiomethoxymethyl; R_, R 11 and R, g are hydrogen; R g is isobutyl or cyclohexylmethyl; and R, 2 is loweralkyl, aminoalkyl or dialkylaminoalkyl. 6. A compound according to Claim 2 wherein A is (morpholin-4-yl)carbony1-CH 2 ; R. is benzyl; W is carbonyl; U is NH; R 3 is (imidazol-4-yl)methyl; R β is cyclohexylmethyl; V is S0 2 and R. Q is isopropyl. 7. A compound according to Claim 2 wherein A is BocNH; R^ ^ is benzyl; W is carbonyl; U is NH; 3 is (imidazol-4-yl)methyl; R g is cyclohexylmethyl; V is" CH 2 and R 1Q is isopropyl. 8. A compound according to Claim 3 wherein A is BocNH; R χ is benzyl; W is carbonyl; U is NH; 3 is isobutyl; R g is cyclohexylmethyl; R-_ is C=0, R 14 is CF 2 ; M is S0 2 and R.- is isopropyl. 9. A compound according to Claim 3 wherein A is BocNH; R χ is benzyl; W is carbonyl; U is NH; R 3 is pyrazol-3-ylmethyl; R g is cyclohexylmethyl; R 13 is CHOH; χ4 is CH 2 ; M is NHC=0 and R 1Q is CH 2 CH 2 -isopropyl. 9. A compound according to Claim 4 wherein wherein A is 3,4-dihydroxypyrrolidinocarbonylamino; R 1 is benzyl; W is C=0; U is NH; 3 is thiomethoxymethyl; R g is cyclohexylmethyl; P is hydrogen; and R lg is sec-butyl. 10. A compound according to Claim 4 wherein wherein A is BocNH; R. is benzyl; W is C=0; U is NH; 3 is thiomethoxymethyl; R- is 1,3-dithiolan- 2-ylmethyl; P is hydrogen; and R ιg is sec-butyl. 11. A compound according to Claim 5 wherein A is 6-aminohexanoyl-NH; R 1 is benzyl; W is C=0; U is NH; 3 is imidazol-4-ylmethyl; R g is cyclohexyl¬ methyl; n is 0; T is methylidene; and R, 2 is 3-methylbutyl. 12. A compound according to Claim 5 wherein A is BocNH; R. is benzyl; W is C=0; U is NH; 3 is imidazol-4-ylmethyl; R g is cyclohexylmethyl; n is 1; S is OH; T is C1CH 2 ; and R, 2 is isobutyl. 13. A pharmaceutical composition for treating renin-associated hypertension comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of Claim 1. 14. A method of treating hypertension comprising administering to a host in need of such treatment a therapeutically effective amount of the compound of Claim 1.

Inventors: DELLARIA JOSEPH, FUNG ANTHONY K L, KEMPF DALE JOHN, LULY JAY RICHARD, PLATTNER JACOB JOHN, ROSENBERG SAUL HOWARD, SHAM HING LEUNG, DELLARIA, JOSEPH, FUNG, ANTHONY, K., L., KEMPF, DALE, JOHN, LULY, JAY, RICHARD, PLATTNER, JACOB, JOHN, ROSENBERG, SAUL, HOWARD, SHAM, HING, LEUNG
Applicants: DELLARIA JOSEPH, FUNG ANTHONY K L, KEMPF DALE JOHN, LULY JAY RICHARD, PLATTNER JACOB JOHN, ROSENBERG SAUL HOWARD, SHAM HING LEUNG, DELLARIA, JOSEPH, FUNG, ANTHONY, K., L., KEMPF, DALE, JOHN, LULY, JAY, RICHARD, PLATTNER, JACOB, JOHN, ROSENBERG, SAUL, HOWARD, SHAM, HING, LEUNG
Application year: 1987
Main classification: A61K37
IPC codes: A61K38, C07C67, C07C235, C07C237, C07C239, C07C253, C07C255, C07C271, C07C301, C07C307, C07C309, C07C311, C07C313, C07C317, C07C323, C07D207, C07D231, C07D233, C07D263, C07D295, C07D317, C07D319, C07D339, C07D405, C07D409, C07K5, C07K14, C12N9