bluuebunny/crossref_metadata_2025 huggingface dataset:
[(1,3‐Dioxolan‐2‐yliden)methyl]phosphonate und ‐phosphinate als (einfache) Synthone in der Heterocyclensynthese
Authors: Neidlein Richard , Eichinger Thomas
Published: December 2004

[(1,3‐Dioxolan‐2‐ylidene)methyl]phosphonates and ‐phosphinates as [simple] Synthons in Heterocyclic Synthesis

The readily available [(1,3‐dioxolane‐2‐ylidene)methyl]phosphonates and ‐phosphinates 2a–f (Scheme 1) can be transformed with amines to aliphatic ketene N,O‐and N,N‐acetales (see Scheme 2, 2a → 3–7). Alkanediamines yield with 2a–f the imidazolidines 8a–f and the hexahydropyrimidines 9a–d (Scheme 3). the oxazolidine derivatives 10a–e and the thiazolidine 11 are accessible under special reaction conditions starting from 2a, b (Scheme 4). Hydrazines react with the CN‐group‐containing ketene O,O‐acetals 2a–c to the pyrazoles 12a–g, whereof 12a, d, e can be cyclized to pyrazolo[1,5‐a]pyrimidines 13a–d (Scheme 5). Amidines as starting materials transform 2a–c in an analogous way to the pyrimidine derivatives 14a–c (Scheme 6).
Thermodynamic Enantioface‐Binding Selectivities of Monosubstituted Alkenes to a Highly Discriminating Chiral Transition ‐Metal Lewis Acid; equilibration of diastereoisomeric (cyclopentadienyl)(alkene)(nitrosyl)(triphenylphosphine)rhenium complexes ([Re(η5–C5H5)(CH2 = CHR)(NO) (PPh3)]+BF)
Authors: Peng Tang‐Sheng , Arif Atta M. , Gladysz John A.
Published: December 2004

Reactions of monosubstituted alkenes RCH = CH2 and [Re(η5–C5H5)(CH2Cl2) (NO)(PPh3)]+BF give complexes ([Re(η5–C5H5))(CH2CHR)(NO) (PPh3)]+BF (1a–g) in 63–99% yields as mixtures of (RS,SR)‐ and (RR,SS)‐diastereoisomers (1a (R = Me), 66:34; 1b (R = Pr), 63:37; 1c (R = PhCH2), 70:30; 1d (R = Ph), 75:25; 1e (R = i‐Pr), 64:36; 1f (R = t‐Bu), 84:16; 1g (R = Me3Si), 69:31; Scheme 2). These differ in the CC enantioface bound to the chiral Re fragment. In most cases, the analogous reactions of RCHCH2 and [Re(η5–C5H5) (C6H5Cl)(NO)(PPh3)]+ BF give comparable results. When 1a–e, g are heated in PhCl at 95–100°, equilibration to 96:4, 97:3, 97:3, 90:10, > 99:< 1, and > 99:< 1 (RS,SR)/(RR,SS) mixtures occurs (79–99% recoveries; Tables 1 and 2). Thus, thermodynamic enantioface‐binding selectivities are much higher than kinetic binding selectivities. This phenomenon is analyzed in detail. A crystal structure of (RS,SR)‐1e (monoclinic, P21/c, a = 10.256(1) Å. b = 17.191(1) Å, c = 16.191(1) Å, β = 101.04(1)°, Z = 4) shows that the Re–C(1)–C(2) plane (see Fig.2) is nearly coincident with the Re–P bond (angle 15°), and that the i‐Pr group is ‘syn’ to the nitrosyl ligand.
O‐Insertion into Nonactivated CH Bonds: The first observation of O2 cleavage by a P‐450 enzyme model in the presence of a thiolate ligand
Authors: Patzelt Heiko , Woggon Wolf‐Dietrich
Published: December 2004

On reaction with ‘O’‐donors or O2, the synthetic P‐450 analogue 2 undergoes O‐insertion at a nonactivated CH bond of the covalently bound substrate. The mechanism of O‐insertion with O2 most likely involves homolytic cleavage of the OO bond followed by O‐insertion via radical recombination.
Eine neue einfache Synthese spirocyclischer 1H‐Chinolin‐Derivate
Authors: Walter Harald , Sauter Hanspeter , Winkler Tammo
Published: December 2004

A New and Simple Method for the Synthesis of Spirocyclic la‐Quinolines

The reaction of anilines with (+)‐(R)‐pulegone in toluene at temperatures between 125 and 150° with 4‐toluenesulfonic acid or I2 as catalysts leads to diastereoisomeric mixtures of spiro[cyclohexane‐1,2′(1′H)‐quinoline] derivatives (see 1–4, Scheme 1; Table). The diastereoisomers are separated by column chromatography, and the structure of the single isomers is determined by NMR‐spectroscopic methods. A reaction mechanism proceeding via several 6π‐electrocyclic rearrangements and H‐shifts is proposed for the formation of 1H‐quinolines 1–4 (Scheme 2). This mechanism is in accordance with the results of the reaction of 2‐isopropenylaniline with 3‐methylcyclohexanone which leads to a stereoisomeric mixture of 3,4′‐dimethylspiro[cyclohexane‐1,2′(1H)‐quinolines] (Scheme 3).
Warum Pentose‐ und nicht Hexose‐Nucleinsäuren??. Teil II. Oligonucleotide aus 2′,3′‐Dideoxy‐β‐D‐glucopyranosyl‐Bausteinen (‘Homo‐DNS’): Herstellung.
Authors: Böhringer Markus , Roth Hans‐JÖRg , Hunziker Jürg , Göbel Michael , Krishnan Ravichandran , Giger Alfred , Schweizer Bernd , Schreiber Jakob , Leumann Christian , Eschenmoser Albert
Published: December 2004

Why Pentose and Not Hexose Nucleic Acids? Part II.
Preparation of Oligonucleotides Containing 2′,3′‐Dideoxy‐β‐D‐glucopyranosyl Building Blocks(7)

This paper describes the preparation of the 2′,3′‐dideoxy‐β‐D‐glucopyranosyl‐( = 2′,3′‐dideoxy‐β‐D‐erythro‐hexopyranosyl)‐derived nucleosides of the five bases adenine, cytosine, guanine, thymine, and uracil ( = ‘homo‐de‐oxyribonucleosides’) as well as the synthesis of oligonucleotides derived from them. The methods used for both nucleoside and oligonucleotide synthesis closely follow the known methods of synthesis in the corresponding series of natural 2′‐deoxyribonucleosides and oligonucleotides. The efficient methods of automated DNA synthesis proved to be fully applicable to the synthesis of homo‐DNA oligonucleotides, the only change necessary for achieving satisfactory coupling yields being a slight lengthening of the coupling time. Homo‐DNA oligonucleotides with chain lengths of up to twelve nucleoside units were assembled on solid support either manually or on a commercial DNA synthesizer in scales of 0.4 μmol to as much as 200 μmol and were purified by either reversed‐phase or ion‐exchange HPLC to single‐peak purity according to both chromatographic systems (estimated purity > 95%). The choice of the specific base sequences to be synthesized was determined primarily by the constitutional problems of base pairing that emerged from experimental observations made in the course of systematic studies of the pairing properties of homo‐DNA oligonucleotides. About 100 homo‐DNA sequences were prepared for this purpose. Their pairing properties will be described in Part III of this series; the present paper is restricted to the characterization of the purity and constitutional integrity of a few selected (single‐stranded) oligonucleotides by 1H‐, 31P‐, and 13C‐NMR spectroscopy as well as by FAB and time‐of‐flight mass spectroscopy.

The English Footnotes to Schemes 1–9, Fig. 1–12, and Table 1 provide an extension of this summary.
3‐Deaza‐2′‐deoxyadenosine: Synthesis via 4‐(methylthio)‐1H‐imidazo[4,5‐c]pyridine 2′‐deoxyribonucleosides and properties of oligonucleotides
Authors: Seela Frank , Grein Thomas , Samnick Samuel
Published: December 2004

The synthesis of 4‐(methylthio)‐1H‐imidazo[4,5‐c]pyridine 2′‐deoxy‐β‐D‐ribonucleosides 2 and 9 and the conversion of the N1‐isomer 2 into the 2′,3′‐didehydro‐2′,3′‐dideoxyribonucleoside 3a or (via 7) 3‐deaza‐2′‐deoxyadenosine (1) is described. Phosphonate building blocks of 1 were employed in solid‐phase synthesis of self‐complementary base‐modified oligonucleotides. Their properties were studied with regard to duplex stability and hydrolysis by the restriction enzyme Eco RI.
A Ring‐Enlargement Reaction Yielding 1,2,5‐Benzothiadiazonin‐6‐one 1,1‐Dioxides
Authors: Orahovats Alexander S. , Linden Anthony , Heimgartner Heinz
Published: December 2004

At room temperature or under reflux in MeCN, 3‐amino‐2H‐azirines 2 and 3,4‐dihydro‐2H‐1,2‐benzothiazin‐3‐one 1,1‐dioxide (4) give 1,2,5‐benzothiadiazonin‐6‐one 1,1‐dioxides5 in fair‐to‐good yield (Scheme 2). The structure of this novel type of heterocyclic compounds has been established by X‐ray crystallography of 5a (Fig.). A ring expansion via a zwitterionic intermediate of type A' is proposed as the reaction mechanism of the formation of 5.
Ruthenium‐Catalyzed Enantioselective Hydrogenation of 1,3‐O‐Disubstituted 1,3‐Dihydroxypropan‐2‐ones
Authors: Cesarotti Edoardo , Antognazza Patrizia , Mauri Angela , Pallavicini Marco , Villa Luigi
Published: December 2004

Optically active 1,3‐O‐disubstituted glycerols were obtained by enantioselective homogeneous hydrogenation of the corresponding 1,3‐O‐disubstituted 1,3‐dihydroxypropan‐2‐ones with different RuII‐binap complexes. The highest enantioselectivities were obtained with dimeric chloro‐ruthenium complexes on the substrates bearing bulky trityloxy groups.
A New Asymmetric Synthesis of Tricarbonylchromium Complexes of ortho‐Substituted Benzaldehydes. Preliminary communication
Authors: Kündig E. Peter , Liu Ronggang , Ripa Alberto
Published: December 2004

ortho‐Substituted [Cr(CO)3(benzaldehyde)] complexes are obtained via nucleophilic addition of alkyl‐ and aryllithium reagents to a [Cr(CO)3(phenylmethaneimine)] complex followed by endo‐hydride abstraction with triphenylmethyl cation. This sequence, when carried out with a [Cr(CO)3(benzaldehyde SAMP hydrazone)] complex affords substituted derivatives (Me, Bu, Ph, vinyl) with high (⩾97%) diastereoselectivity and, after hydrolysis, ortho‐ substituted [Cr(CO)3(benzaldehyde)] ((S)‐1) complexes of high enantiomeric purity.
New Monoterpene‐Substituted Dihydrochalcones from Piper aduncum
Authors: Orjala Jimmy , Wright Anthony D. , Erdelmeier Clemens A. J. , Sticher Otto , Rali Topul
Published: December 2004

Five New unusual monoterpene‐substituted dihydrochalcones, the adunctins A–E (1″S)‐1‐{2′‐hydroxy‐4′‐methoxy‐6′‐[4″‐methyl‐1″‐(1‴‐methylethyl)cyclohex‐3″ ‐en‐1″ ‐yloxy]phenyl}‐3‐phenylpropan‐1‐one (1), (5aR*,8R*,9aR*)‐3‐phenyl‐1‐[5′,8′,9′,9′a‐tetrahydro‐3′‐hydroxy‐1′‐methoxy‐8′‐(1″‐methylethyl)‐5′‐a‐methyldibenzo‐[b,d]furan‐4′‐yl]propan‐1‐one (2), (2′R*,4″S*)‐1‐{6′‐hydroxy‐4′‐methoxy‐4″‐(1‴‐methylethyl)spiro[benzo[b]‐furan‐2′(3′H),1″ ‐cyclohex‐2″ ‐en]‐7′‐yl}‐3‐phenylpropan‐1‐one (3), (2′R*,4″R*)‐1‐{6′‐hydroxy‐4′‐methylethyl‐4″‐(1‴‐methylethyl)spiro[benzo[b]furan‐2′(3′H),1″‐cyclohex‐2″‐en]‐7′‐yl}‐3‐phenypropan‐1‐one (4), and (5′aR*,6′S*, 9′R*,9′aS*)‐1‐[5′a,6′,7′,8′,9′a‐hexahydro‐3′,6′‐methoxy‐6′‐methyl‐9′‐(1″‐methylethyl)dibenzo[b,d]‐furan‐4′‐yl]‐3‐phenylpropan‐1‐one (5) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (−)‐methyllindaretin (6), trans‐phytol, and α‐tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D‐ and 2D‐NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.
Application of Electrospray Mass Spectrometry for Characterizing Supramolecular Coordination Complexes
Authors: Hopfgartner Gérara , Henion Jack D. , Piguet Claude , Williams Alan F.
Published: December 2004

The Electrospray Mass Spectrometry (ES‐MS) of eight different supramolecular complexes shows that the molecular peaks of the desolvated multiply charged cations can be recorded more easily than by Fast‐Atom‐Bom‐bardment Mass Spectrometry (FAB‐MS) measurements of similar compound. The preliminary application of the ES‐MS technique to self‐assembled helical complexes obtained from ligands L3 to L8 with various metal ions (Cu, Co, Eu, Tb) indicates that ES mass spectra qualitatively reflect the species present MeCN solution.
Glyconothio‐O‐lactones Part II. Cycloaddition to Dienes, Diazomethane, and Carbenoids
Authors: Hürzeler Marianne , Bernet Bruno , Mäder Thomas , Vasella Andrea
Published: December 2004

The addition of dienes, diazomethane, and carbenoids to the manno‐ and ribo‐configurated thio‐γ‐O‐lactones 1 and 2 was investigated. Thus, 1 (Scheme 1) reacted with 2,3‐dimethylbutadiene (→ 4, 73%), cyclopentadiene (→ 5a/b 1:1, 70%), cyclohexa‐ 1,3‐diene (→ 9a/b 2:3, 92%), and the electron‐rich butadiene 6(→7a/b 3:1, 82%). Wheras 5a/b was separated by flash chromatography, 7a/b was desilylated leading to the thiapyranone 8. Selective hydrolysis of one isopropylidene group of 9a/b and flash chromatography gave 10a and 10b. The structures of the adducts were elucidated by X‐ray analysis (4), by NOE experiments (4, 5a, 5b, 7a/b, 10a, and 10b), and on the basis of a homoallylic coupling (7a/b). The additions occurred selectively from the ‘exo’ ‐side of1. Only a weak preference for the ‘endo’‐adducts was observed. Hydrogenation of 9a/b with Raney‐Ni (EtOH, room temperature) gave the thiabicyclo [2.2.2]octane 11. Under harsher conditions (dioxane, 110°), 9a/b was reduced to the cyclohexyl ß‐DC‐glycoside 12 which was deprotected to 13. X‐Ray analysis of 13 proved that the desulfuration occurred with inversion of the anomeric configuration. The regioselective addition of the dihydropyridine 14 to 1 (Scheme 2) and the methanolysis of the crude adduct 15 gave the lactams 16a (32%) and 16b (38%). Desilylation of 15 with Bu4NF · 3H2O, however, gave the unsaturated piperidinedione 17 (92%) which was deprotected to the tetrol 18 (65%). Similarly, 2 was transformed via 19 (62%) into the triol 20 (74%). The cycloaddition of 1 with CH2N2 (Scheme 3) gave a 35:65 mixture of the 2,5‐dihydro‐ 1,3,4‐triazole 21and the crystalline 4,5‐dihydro 1,2,3‐triazole 22. Treatment of 21 and 22 with base gave the hydroxytriazoles 23 and 24, respectively. The structure of 24 was established by X‐ray analysis. The triazole mixture 21/22 was separated by prep. HPLC at 5°. At room temperature, 21 already decomposed (half‐life 21.6 h) leading in CDCI3 solution to a complex mixture (containing ca. 20–25% of the spirothiirane 27 and ca. 7–10% of its anomer) and in MeOH solution exclusively to the O,O,S‐ortholactone 26. Crystals of 22 proved be stable at 105°. Upon heating in petroleum ether at 100°, 22 was transformed into a ca. 1:1 mixture of 27 and the enol ether 28. The reaction of 1 with ethyl diazoacetate (Scheme 4) in the presence of Rh2(OAc)4. 2H2O gave the unsaturated esters 29 (33%) and 30 (26%), whereas the analogous reaction with diethyl diazomalonate afforded the spirothiirane 31 (68%) and the enol ether 32 (29%). Complete transformation of 31 into 32 was achieved by the treatment with P(NEt2)3. Similary, 33 (69%) was prepared from 2.
Synthesis and Absolute Configuration of the C12‐Terpenoid Dehydrogeosmin from the Flower Scents of Rebutia marsoneri and Dolichothele sphaerica (Cactaceae); a new approach to bis‐angularly substituted trans‐decalins
Authors: Huber Udo , Boland Wilhelm , König Wilfried A. , Gehrcke Bärbel
Published: December 2004

Optically pure(+)‐(4S, 4aS, 8aS)‐1,2,3,4,4a,5,8,8a‐octahydro‐4,8a‐dimethylnaphthalen‐4a‐ol((+)‐1; dehydrogeosmin) is released from flower heads of the two cactaceae Rebutia marsoneri and Dolichothele spharica. The absolute configuration of (+)‐1 is identical with that of the known microbial metabolial geosmin (−)‐2. The key reactions of the synthesis of 1 are the kinetically controlled transesterification of the primary alcohol 4 using a lipase from Candida cyclindracea and the stereo‐and regiospecific angular alkylation of a cis‐decalin skeleton by a Lewis‐acid‐assisted ring opening of the quaternary epoxy‐alcohol 3 with MeMgBr/Cul. The sequence provides a new entry into the class of bis‐angularly substituted trans‐decalins.
Synthesis and Monoamine Oxidase Inhibitory Activity of 3‐Substituted 5H‐Indeno[1,2‐c]pyridazines
Authors: Kneubühler Silvia , Testa Bernard , Carta Vincenzo , Altomare Cosimo , Carotti Angelo
Published: December 2004

The one‐pot synthesis of nine 5H‐indeno[1,2‐c]pyridazines is described. These compounds are shown to be potent, reversible inhibitors of monoamine oxidase B (MAO‐B) with little or no effect on monoamine oxidase A (MAO‐A). Qualitative structure‐activity relations indicate that the MAO‐B inhibitory activity is strongly influenced by electronic and bulk properties of substitutents.
8‐Azaguanine 2′,3′‐Dideoxyribonucleosides: Glycosylation of the 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidinyl anion with 2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride
Authors: Seela Frank , Mersmann Karin
Published: December 2004

The synthesis of the regioisomeric 8‐azaguanine N7‐, N8‐, and N9‐(β‐D‐2′,3′‐dideoxyribonucleosides) (1, 2, and 3, respectively) and of the diamino derivative 13 is described. The anion of 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (5) was glycosylated with 5‐O‐[(tert‐butyl)dimethylsilyl]‐2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride (6; anomeric mixture), yielding the regioisomeric 2′,3′‐dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a, and 9a/12a. They were desilylated with Bu4NF in THF affording the 5‐amino‐7‐methoxy‐nucleosides 7b–12b. Treatment with aqueous NaOH gave the 8‐azaguanine β‐D‐2′,3′‐dideoxynucleosides 1–3 and their α‐D‐anomers 14–16. The reaction of 7b with NH3/MeOH yielded the diamino compound 13. The N‐glycosylic bond of 8‐aza‐2′,3′‐dideoxyguanosine (1) is four‐times more stable against acid than that of 2′,3′‐dideoxyguanosine. Compounds 1, 2, and 13 were converted to their 5′‐triphosphates 17–19 which showed only modest inhibitory activity against HIV‐reverse transcriptase.
Synthesis of a Fullerene Derivative of Benzo[18]crown‐6 by Diels‐Alder Reaction: Complexation Ability, Amphiphilic Properties, and X‐Ray Crystal Structure of a Dimethoxy‐1,9‐(methano[1,2]benzenomethano)fullerene[60] Benzene Clathrate
Authors: Diederich François , Jonas Ulrich , Gramlich Volker , Herrmann Andreas , Ringsdorf Helmut , Thilgen Carlo
Published: December 2004

A fullerene derivative 1 of benzo[18]crown‐6 was obtained by Diels‐Alder addition of fullerene[60](C60) to the ortho‐quinodimethane prepared in situ from 4,5‐bis(bromomethyl)benzo[18]crown‐6 (3) with Bu4NI in toluene. Extraction experiments show that the complexation of K+ ions strongly increases the solubility of 1 in protic solvents like MeOH. Using Langmuir‐Blodgett techniques, monolayers of the highly amphiphilic fullerene‐derived crown ether 1 and its K+ ion complex were prepared. An X‐ray crystal structure was obtained from a benzene clathrate of comparison compound 2, synthesized by Diels‐Alder reaction of C60 with the ortho‐quinodimethane derived from 1,2‐bis(bromomethyl)‐4,5‐dimethoxybenzene (4). Both the fullerene molecule 2 and the benzene molecule are fully ordered in a crystal packing which is stabilized by intermolecular van‐der‐Waals contacts between the benzene ring and the C‐spheres, intermolecular C…︁C contacts between the C60 moieties, and intermolecular O…︁C contacts between the O‐atoms of the veratrole moieties and fullerene C‐atoms.
Enantioselective Synthesis of (2S)‐2‐Amino‐3‐(4‐hydroxy‐3‐phosphonophenyl)propionic Acid (= 3′‐Phosphono‐L‐tyrosine) and Its Incorporation into Peptides
Authors: Paladino Joseph , Guyard Christel , Thurieau Christophe , Fauchère Jean‐Luc
Published: December 2004

The asymmetric synthesis of derivatives of the new amino acid (2S)‐2‐amino‐3‐(4‐hydroxy‐3‐phosphono‐phenyl)propionic acid (3′‐phosphono‐L‐tyrosine; Tyr [3′‐PO(OH)2]) is described. The protected amino acid 13 is obtained via a Schöllkopf synthesis by coupling of the rearranged ortho‐phosphonophenolic side chain (see Scheme 1, 6a) with the lithiated bis‐lactim ether 8 of cyclo(‐D‐valyl‐glycyl‐) (see Scheme 2). The incorporation of the protected amino acid 14 in a biologically active dodecapeptide is successfully achieved by the [(9H‐fluoren‐9‐yl)‐methoxy]carbonyl (Fmoc) strategy of solid‐phase peptide synthesis. Differential protection of Tyr[3′‐PO(OH)2] provides four levels of selective deprotection of, in the order, the N2‐amino, the carboxyl (cleavage from the resin), the phenol, and the phosphono function (→ peptide 16).
Regioselective Radical Additions to 7‐Oxabicyclo[2.2.1]hept‐5‐en‐2‐one
Authors: Vionnet Jean‐Paul , Schenk Kurt , Renaud Philippe
Published: December 2004

Radical addition to 7‐oxabicylco[2.2.1]hept‐5‐en‐2‐one (1) was examined from a regiochemical point of view, and despite the small electronic anisotropy of the double bond, electrophilic radicals were found to add preferentially at C(5) with selectivities of up to 5:1. We also report the first case of an inversion of the regioselectivity of a radical reaction using Lewis acids.
D‐Gluconhydroximo‐1,5‐lactam and Related N‐Arylcarbamates Theoretical Calculations, Structure, Synthesis, and Inhibitory Effect on β‐Glucosidases
Authors: Hoos Roland , Naughton Andrew B. , Thiel Walter , Vasella Andrea , Weber Wolfgang , Rupitz Karen , Withers Stephen G.
Published: December 2004

The known D‐gluconhydroximo‐1,5‐lactam (= D‐glucono‐1,5‐lactam oxime) 7a, its nitrogen isotopomers 7b and 7c, and the N‐arylcarbamates 26–29 were synthesized from 2,3,4,6‐tetra‐O‐benzyl‐D‐glucono‐1,5‐lactam (11a) and its nitrogen isotopomer 11b to establish the controversial structure of 7a and to study the inhibition of β‐glucosidases by the N‐arylcarbamates 26–29. Conversion of 11a with Lawesson's reagent yielded a mixture of the thionolactam 15a and its manno‐configurated isomer 16a, which was transformed into a mixture of the benzylated hydroximo‐lactam 13a and the manno‐isomer 17a. Debenzylation (Na/NH3) and acetylation of this mixture led to the gluco‐configurated pentaacetate 14a and the manno‐isomer 18a. Treatment of 11a with Et3O·BF4 and then with H2NOH gave exclusively the benzylated D‐gluconhydroximo‐1,5‐lactam (benzylated D‐nojirilactam oxime) 13a, which was transformed into 14a. Deacetylation of 14a yielded the hydroximo‐lactam 7a. The isotopomers 7b and 7c were obtained by analogous reaction sequences, using either 15NH3 or 15NH2OHHCl. To prepare the acetylated N‐arylcarbamates 20–25, 13a was debenzylated and acetylated (→ 14a), followed by selective deacetylation to the tetraacetate 19a and treatment with the appropriate isocyanates. The structure of the 2‐chlorophenyl carbamate 21 was established by X‐ray analysis. Deacetylation of 20–23 led to the N‐arylcarbamates 26–29.

The 15N‐NMR spectra of 7b, 7c, and of their precursors 13b, 13c, 14b, and 14c, show that the CN bond in all these lactam oximes is exocyclic as predicted from semiempirical and ab initio SCF‐MO calculations on the structure of acetamide oxime and 5‐pentanelactam oxime. According to these calculations, 5‐pentanelactam oxime is a (Z)‐configurated, flattened chair. X‐ray analysis established the structure of D‐glucono‐1,5‐lactam oxime (7a) in the solid state, where it adopts a conformation between 4C1 and 4H3. In H2O, 7a is a flattened 4C1. The calculations also predict that protonation at the exocyclic N‐atom strengthens the conjugation between the endocyclic N‐atom and the hydroxyimino group, and leads to a half‐chair conformation. This is evidenced by the chemical shift differences in the 15N‐NMR spectra observed upon protonation of 7b and 7c. The hydroximolactam 7a and the N‐arylcarbamates 26–29 are competitive inhibitors of the β‐glucosidases from sweet almond (emulsin) and from Agrobacterium faecalis (= Abg), with KI values between 8 and 21·10−6M against emulsin (at pH 6.8) and between 0.15 and 1.2·10−6M against Abg (at pH 7.0).
A New Approach to 5‐Thiosugars: 5‐Thio‐D‐Gluconhydroximo‐1,5‐lactone, Synthesis and Evaluation as β‐Glucosidase Inhibitor
Authors: Ermert Philipp , Vasella Andrea
Published: December 2004

The thiolactone oxime 10 was synthesized in ten steps from the known tri‐O‐benzylglucose 13, which was transformed into the oxime 14, silylated (→ 15), and mesylated (→ 16). Treatment of 16 with Bu4NF yielded the L‐ido‐epoxide 17 and the hydroxylamine 18; the isomeric D‐gluco‐configurated hydroxylamine 20 was prepared from 17. Reaction of 17 with thiourea yielded the thiirane 19. Ring opening was best effected with HBr (→ 22·HBr). The N‐glycosylhydroxylamine 22 was immediately oxidized to 24, as it reverted to 19. Similarly, 19 was transformed into the chlorides 21 and 23. The iodide 25 reacted with TEMPO to afford 29 besides 26 and 30; nucleophilic substitution of 23, 24, or 25 gave unsatisfactory yields of 26 or 27, and 28. Birch reduction transformed 29 into 10 which was isolated via the pentaacetate 32, which was also transformed into the tetraacetate 33. The weak activity of 10 as an inhibitor of sweet‐almond and Agrobacter β‐glucosidase is in keeping with categorization of the lactone and lactam oximes 1–5 and the 5‐thiosugars 6–9 as transition‐state and substrate analogs, respectively.
Chemo‐enzymatic Synthesis of 6″‐O‐(3‐Arylprop‐2‐enoyl) Derivatives of the Flavonol Glucoside Isoquercitrin
Authors: Danieli Bruno , Bertario Andrea , Carrea Giacomo , Redigolo Barbara , Secundo Francesco , Riva Sergio
Published: December 2004

A chemo‐enzymatic approach to some 6″‐O‐(3‐arylprop‐2‐enoyl) derivatives of the flavonol glucoside isoquercitrin (2a) was explored to overcome the inability to directly introduce these acyl moieties by an enzyme‐catalyzed reaction of 2a with the corresponding activated esters. This new approach was based on the regioselective introduction of a methyl malonate residue at the CH2OH of the sugar moiety by catalysis with the protease subtilisin (→ 22a). The mixed diester 22a was then subjected to chemoselective hydrolysis of the methoxycarbonyl function by another enzyme, biophine esterase (→ 23). Finally, the malonic monoester 23 was reacted in a Knoevenagel‐type condensation with benzaldehyde, 4‐hydroxybenzaldehyde, or 4‐hydroxy‐3‐methoxybenzaldehyde to afford the target 6″‐O‐(3‐arylprop‐2‐enoyl) isoquercitrins 2b–d.
Nucleotides. Part XLII. The 2‐dansylethoxycarbonyl (= 2‐{[5‐(dimethylamino)naphthalen‐1‐yl]sulfonyl}ethoxycarbonyl; dnseoc) group for protection of the 5′‐hydroxy function in oligoribonucleotide synthesis
Authors: Bergmann Frank , Pfleiderer Wolfgang
Published: December 2004

The 2‐dansylethoxycarbonyl (Dnseoc) group was employed for protection of the 5′‐hydroxy function in oligoribonucleotide synthesis by the phosphoramidite approach using the acid‐labile tetrahydro‐4‐methoxy‐2H‐pyran‐4‐yl (Thmp) group for 2′‐protection. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside‐functionalized supports, are described for the four common nucleosides adenosine, guanosine, cytidine, and uridine, and for the two modified minor nucleosides ribothymidine (= ribosylthymine) and pseudouridine.
Oligosaccharides Related to Tumor‐Associated Antigens. Part I. Synthesis of the propyl glycoside of the trisaccharide α‐L‐Fucp‐(1 → 2)‐β‐D‐Galp‐(1 → 3)‐β‐D‐GalpNAc, component of a tumor antigen recognized by the antibody MBr1
Authors: Lay Luigi , Nicotra Francesco , Panza Luigi , Russo Giovanni , Adobati Elena
Published: December 2004

The synthesis of the trisaccharide α‐L‐Fucp‐(1 → 2)‐β‐D‐Galp‐(1 → 3)‐β‐D‐GalpNAc‐1‐OPr (2) is described. The N‐acetylgalactosamine 6 was obtained from 4 by an intramolecular displacement of a (trifluoromethyl)sulfonyloxy by a pivaloyloxy group with its concomitant migration from position 3 to position 4 (Scheme 1). The galactosyl donor 9 was obtained from 7 via 8 by regioselective opening of the orthoester function with AcOH/pyridine followed by treatment with CCl3CN and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) (Scheme 2). Glycosylation of 6 with 9 in the presence of BF3 · OEt2 gave the disaccharide 10. Selective deprotection of 10 at OC(2′) followed by glycosylation with 12 and by standard deprotection afforded the title trisaccharide 2 (Scheme 3). Preliminary biological testing showed that 2 is able to inhibit the binding of the monoclonal antibody MBrl to the target tumor cells MCF7 in a dose‐dependent manner.
Diastereo‐ and Enantiocontrolled Synthesis of (–)‐Allosedamine via Cycloaddition of a Chiral Nitrone
Authors: Oppolzer Wolfgang , Deerberg Jörg , Tamura Osamu
Published: December 2004

The piperidine alkaloid (–)‐allosedamine (1) has been synthesized, in 21% overall yield, in nine steps starting from the formyl‐ester 4. The synthesis features the reaction cascade 7 → 3 → 2, involving asymmetric electrophilic enolate hydroxyamination, hydroxylamine/aldehyde condensation, and nitrone/styrene cycloaddition, as well as the reductive N/O cleavage‐decyanation 12 → 1.
Glycosylidene Carbenes. Part 16. Glycosidation of methyl 6‐O‐trityl‐α‐D‐altropyranoside
Authors: Bozó Eva , Vasella Andrea
Published: December 2004

Hydrogen bonding of the triol 4 in chlorinated solvents was studied by IR (CH2Cl2 and CCl4) and 1H‐NMR spectroscopy (CDCl3), and the regioselectivity of the glycosidation of the triol 4 by the diazirine 1 is predicted on the basis of two assumptions: preferred protonation of the intermediate glycosylidene carbene by the OH group involved in the weakest intramolecular H‐bond, and attack in the π‐plane of the thereby generated oxycarbenium cation either by the reoriented oxy anion, or by a properly oriented vicinal OH group. Glycosidation led to the disaccharides 5–10 (Scheme) which were separated and characterized as their acetates 11–16, to the lactone azines 17 and to the 2‐(benzyloxy)glucal 18. In agreement with the predictions, glycosidation in non‐coordinating solvents gave the 1,2‐, 1,3‐, and 1,4‐linked disaccharides in decreasing relative amounts. Glycosidation in THF proceeded with a lower degree of regioselectivity and led preferentially to the β ‐D‐anomers, except for the minor, 1,4‐linked disaccharides, where THF had only a weak influence on stereoselectivity at room temperature and led to a slight increase of the α ‐D‐anomer at −80°.
A Novel Rearrangement Product of Podophyllotoxone – Ester Derivatives and in vitro cytotoxicity studies
Authors: Höfert Peter H. , Matusch Rudolf
Published: December 2004

A new rearrangement product of podophyllotoxone was obtained by reaction with strong bases. In vitro cytotoxities of this substance and some derivatives were determined using L‐1210 and KB cell lines.
Asymmetric Synthesis of 3‐Hydroxyprolines by Photocyclization of N‐(2‐Benzoylethyl)glycinamides
Authors: Wessig Pablo , Wettstein Philipp , Giese Bernd , Neuburger Markus , Zehnder Margaretha
Published: December 2004

The chiral N‐(2‐benzoylethyl)‐N‐tosylglycinamides 1a‐c were prepared from the C2‐symmetric pyrrolidines 5a‐c. Irradiation of these ketones 1a‐c gave cis‐3‐hydroxyprolinamides 10‐12 in moderate to good yields (Scheme 3). The de of the photocyclizations depended on the size of the substituents in positions C(2) and C(5) of the chiral pyrrolidine auxiliaries. In addition, the de varied with the reaction temperature, allowing the determination of activation‐parameter differences. The structure of products 10‐12 were established by NMR and X‐ray analyses.
Oxidative Coupling of αω,‐Di(cyclopentadienyl)alkane‐diides
Authors: You Shaochun , Gubler Matthias , Neuenschwander Markus
Published: December 2004

The CuII‐induced oxidative coupling of αω,‐di(cyclopentadienyl)alkane‐diides 6 (n = 2–5) has been shown to proceed mainly by an intermolecular pathway to give polymers 8, while the yield of intramolecular coupling 6 → 7 strongly decreases with increasing number n of C‐atoms of the alkyl chain (Scheme 3). For n = 2, intramolecular coupling may be considerably enhanced by replacing the H‐atoms of the CH2CH2 bridge of 6a (n = 2) by Me groups. In this case, intramolecular couplings 11 → 20 (Scheme 7) and 22 → 23 + 24 (Scheme 8) are accomplished with a total yield of 59% and 54%, respectively. All the intramolecular couplings investigated so far proceed stereoselectively to give the C2‐symmetrical cyclohexanes 7a, 20 and 23 with a fixed chair conformation. These results are easily explained, if a conformational equilibrium E ⇄ F is operative in which large substituents R are assumed to enhance the gauche‐conformation F which is the favored conformation for intramolecular couplings. Bridged dihydropentafulvalenes 20 and 23 are quantitatively rearranged to the thermodynamically favored bridged pentafulvenes 27 and 28 under base or acid catalysis, respectively (Scheme 9).
Solution Structure of One‐Electron Reduced and Oxidized Molecules with Twisted Donor and Acceptor Moieties
Authors: Hopf Henning , Kreutzer Martin , Mlynek Cornelia , Scholz Markus , Gescheidt Georg
Published: December 2004

The solution structures of the radical anion and the radical cation of the donor‐acceptor molecules 3,4‐di(1,3‐dithiol‐2‐ylidene)‐4‐phenylbut‐1‐ene‐1,1‐dicarbonitrile (1) and 3,4‐di(1,3‐dithiol‐2‐ylidene)‐4‐phenylbut‐1‐ene‐1,1,2‐tricarbonitrile (2) are discussed based on cyclovoltammetric and ESR/ENDOR measurements. It is shown that the spin population of the radical anions is limited to the di‐ and tricyanoethene moiety and the coplanar 1,3‐dithiole at C(3), whereas that of the radical cations resides mainly inside the two 1,3‐dithiole rings. The energies of the long‐wave bands in the electronic‐absorption spectra of 1 and 2 correspond to the differences between the oxidation and reduction potentials and thus point to a charge‐transfer character of these transitions.
Hoogsteen‐Duplex DNA: Synthesis and base pairing of oligonucleotides containing 1‐deaza‐2′‐deoxyadenosine
Authors: Seela Frank , Wenzel Thomas
Published: December 2004

Oligodeoxyribonucleotides containing 1‐deaza‐2′‐deoxyadenosine ( = 7‐amino‐3‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐3H‐imidazo[4, 5‐b]pyridine; 1b) form Hoogsteen duplexes. Watson‐Crick base pairs cannot be built up due to the absence of N(1). For these studies, oligonucleotide building blocks – the phosphonate 3a and the phosphoramidite 3b – were prepared from 1b via 4a and 5, as well as the Fractosil‐linked 6b, and used in solid‐phase synthesis. The applicability of various N‐protecting groups (see 4a–c) was also studied. The Hoogsteen duplex d[(c1A)20] · d(T20) (11 · 13; Tm 15°) is less stable than d(A20) · d(T20) (12 · 13; Tm 60°). The block oligomers d([c1A)10–;T10] (14) and d[T10–(c1A)10] (15) containing purine and pyrimidine bases in the same strand are also able to form duplexes with each other. The chain polarity was found to be parallel.
Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 10. 14‐O‐Methyl derivatives of 5‐methylnaltrexone and 5‐methylnaloxone
Authors: Schmidhammer Helmut , Nussbaumer Christine , Patel Dinesh , Traynor John R.
Published: December 2004

In several steps, 5, 14‐O‐dimethylnaltrexone (3) and 5, 14‐O‐dimethylnaloxone (4) were prepared starting from 5, 14‐O‐dimethyloxycodone (5). Compound 3 exhibited opioid agonism in vitro (guinea‐pig ileum and mouse vas deferens preparations) and antagonism in vivo (AcOH‐writhing test in mice), while compound 4 was found to be an agonist in vitro and in vivo.
Bildung, Kristallstruktur und absolute Konfiguration von (−)‐N‐(Chloromethyl)galanthaminium‐chlorid
Authors: Matusch Rudolf , Kreh Mirko , Müller Ulrich
Published: December 2004

Formation, X‐Ray Crystal Structure, and Absolute Configuration of (−)‐N‐(Chloromethyl)galanthaminium Chloride

The acetylcholinesterase inhibitor galanthamine (1), main alkaloid of several Narcissus species, readily forms a quaternary ammonium salt by reaction with the solvent CH2Cl2. The structure and absolute configuration of (−)‐N‐(chloromethyl)galanthaminium chloride (2) were determined by X‐ray diffraction (R = 0.075 for 2775 observed independent reflexions) and NMR spectroscopy. The tetragonal crystals (space group P43) contain two crystallographically independent cations which do not differ significantly from one another. The CH2Cl group is attached to the quaternary N‐atom in stereospecific (R)‐configuration. In the crystal, the configurational position of the Me group at the N‐atom of 2 differs from that of the crystalline free base 1. Hydrogen bonding is observed from the OH group at C(3) of 2 to the Cl− anion or to the Cl‐atom of an adjacent cation.
Facile Preparation of (±)‐12‐Epiprostaglandins from 7‐Oxabicyclo[2.2.1]hept‐5‐en‐2‐one via an all‐cis‐formyllactone related to Corey lactone
Authors: Vionnet Jean‐Paul , Renaud Philippe
Published: December 2004

The bicyclic monoselenoacetal 7, easily obtained from (±)‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one (6) via a radical addition‐acyl migration sequence, was converted to racemic 12‐epiprostaglandins 3 and 4. The key intermediate was the all‐cis‐formyllactone 2b related to Corey lactone (see 12; Scheme 1). The presence of a (tert‐butyl)‐dimethylsilyl protective group for the 11‐OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ ‐elimination and epimerization during the Wittig‐Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs.
Thermolysis and Chemiluminescence of Monocyclic 1,2,4‐Trioxan‐5‐ones
Authors: Jefford Charles W. , Josso Martin C. , da Graça H. Vicente Maria , Hagemann Hans R. , Lovy Dominique , Bill Hans
Published: December 2004

The 3,6‐substituted 1,2,4‐trioxan‐5‐ones 11–14, on heating to 170–200°, underwent unimolecular thermolysis to generate electronically excited singlet ketones with an efficiency of ca. 0.2%. The chemiluminescence quantum yields (ϕoSCL) depended on the nature of the 6‐substitutents and increased linearly with temperature. The Arrhenius activation energies were obtained by measuring the rate of decay of luminescence and determined as 22.9, 30.4, 35.6, and 34.2 kcal/mol for 11–14, respectively. Step analysis of the chemiluminescence of 14 afforded an average activation energy of 44.3 kcal/mol. This latter result is explicable in terms of two decomposition paths, higher and lower in energy, leading to excited and ‘dark’ products, respectively. The thermolysis of trioxanones 12–14 lacking a H‐atom at the 6‐position is interpreted as involving successive rupture of the peroxide bond, excision of ketone at the 3‐substituted end, and loss of CO2, to finally produce ketone originating from the 6‐position (see Scheme 4).
Fast‐Atom‐Bombardment Mass Spectra of Phloroglucinols from Dryopteris Ferns
Authors: Widén Carl‐Johan , Pyysalo Heikki , Reichstein Tadeus
Published: December 2004

Fast‐atom‐bombardment mass spectra of ten phloroglucinol derivatives containing two to six ring units were recorded. The mass spectral behavior of the compounds was quite similar under these conditions. Molecular‐weight information was readily available as well as sequential structural data due to extensive fragmentation. Sequential alterations due to the rottlerone change or other analogous decomposition reactions proved to be almost lacking in fast‐atom‐bombardment mass spectrometry. The negative‐ion spectra in general showed better signal‐to‐noise ratios and more distinct fragment ions.
An Efficient Synthesis of Optically Pure (R)‐ and (S)‐2‐(aminomethyl)alanine ((R)‐ and (S)‐ama) and (R)‐ and (S)‐2‐(aminomethyl)leucine ((R)‐ and (S)‐aml)
Authors: Obrecht Daniel , Karajiannis Helena , Lehmann Christian , Schönholzer Peter , Spiegler Clive , Müller Klaus
Published: December 2004

An efficient synthesis of enantiomerically pure (R)‐ and (S)‐2‐(aminomethyl)alanine ((R)‐ and (S)‐Ama) 1a and (R)‐ and (S)‐2‐(aminomethyl)leucine ((R)‐ and (S)‐Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L‐phenylalanine cyclohexylamide (2) as chiral auxiliary. The free amino acids 1a, b were converted to the Nα‐Boc,Nγ‐Z‐protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b, and 9b, the absolute configurations in both series were determined. β‐Turn type‐I geometries were observed for structures 8b and 9b, whereas 8a crystallized in an extended backbone conformation.
Synthetic Studies towards Pseurotin A. Part 3. Synthesis of a related highly functionalized γ‐lactone
Authors: Su Zhuang , Tamm Christoph
Published: December 2004

A new general concept for the total synthesis of pseurotin A (1), a secondary metabolite of Pseudeurotium ovalis STOLK, which possesses a highly substituted 1‐oxa‐7‐azaspiro[4.4]nonane skeleton, is presented. A key intermediate of the planned reaction sequence is the functionalized γ‐lactone 8. The corresponding protected compound 52 was prepared using (S)‐O,O‐isopropylideneglyceraldehyde (13) and the bromoacetal 14 as starting material. γ‐Lactone 52 was obtained in enantiomerically pure state in ten steps. It possesses the desired configuration.
Die Reaktion von 1‐Halogeno‐1‐Lithiocyclopropanen mit CuCl2: Konkurrenz zwischen ‘Carben‐Dimerisierung’ und oxidativer Kupplung
Authors: Borer Markus , Loosli Thomas , Minger Andrea , Neuenschwander Markus , Engel Peter
Published: December 2004

The Reaction of 1‐Halogeno‐1‐lithiocyclopropanes with CuCl2: Competition between ‘Carbene Dimerization’ and Oxidative Coupling

The 1‐chloro‐1‐lithiocyclopropanes 2a–d react at low temperature with CuCl2 to give diastereoisomeric mixtures of oxidative‐coupling products 5a–d and of ‘carbene dimers’ 6a–d. The relative amount of 5a–d increases with CuCl2 concentration and reaction time. Diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoselectivity of the reaction seems to be low, and separation as well as spectroscopic structure assignment of single diastereoisomers are difficult. The conformational behavior of 1,1′‐dichloro‐1,1′‐bi(cyclopropyls) 5c and 5d is discussed. Contrary to 2a–d, 1‐bromo‐1‐lithiocyclopropanes normally react with CuCl2 to give ‘carbene dimers’ 6 and no coupling products 5. So far the only exception is 1‐bromo‐1‐lithio‐2‐phenylcyclopropane 2e which in the presence of CuCl2 gives some percents of coupling products 5e besides carbene dimers 6b as main products. An X‐ray structure analysis of the predominant diastereoisomer 5e was performed.
Nucleosides. Part LIX. The 2‐(4‐nitrophenyl)ethylsulfonyl (Npes) Group: A New Type of Protection in Nucleoside Chemistry
Authors: Pfister Magdalena , Schirmeister Helga , Mohr Marion , Farkas Silke , Stengele Klaus‐Peter , Reiner Tilman , Dunkel Martin , Gokhale Surendra , Charubala Ramamurthy , Pfleiderer Wolfgang
Published: December 2004

The 2‐(4‐nitrophenyl)ethylsulfonyl (npes) group is developed as a new sugar OH‐blocking group in the ribonucleoside series. Its cleavage can be performed in a β‐eliminating process under aprotic conditions using 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as the most effective base. Since sulfonates do not show acyl migration, partial protection of 1,2‐cis‐diol moieties is possible leading to new types of oligonucleotide building blocks. A series of Markiewicz‐protected ribonucleosides 1–10 is converted into their 2′‐O‐[2‐(4‐nitrophenyl)ethylsulfonyl] derivatives 29–38 in which the 5′‐OSi bond can be cleaved by acid hydrolysis forming 39–45. Subsequent monomethoxytritylation leads to 46–50, and desilylation affords the 5′‐O‐(monomethoxytrityl)‐2′‐O‐[2‐(4‐nitrophenyl)ethylsulfonyl]ribonucleosides 51–55. Acid treatment to remove trityl groups do also not harm the npes group (→56–58). Unambiguous syntheses of fully blocked 2′‐O‐[2‐(4‐nitrophenyl)ethylsulfonyl]ribonucleosides 96–102 are achieved from the corresponding 3′‐O‐(tert‐butyl)dimethylsilyl derivatives. Furthermore, various base‐protected 5′‐O‐(monomethoxytrityl)‐ and 5′‐O‐(dimethoxytrityl)ribonucleosides, i.e. 59–77, are treated directly with 2‐(4‐nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2′,3′‐di‐O‐ and the two possible 2′‐ and 3′‐O‐monosulfonates 107–148 which can be separated into the pure components by chromatographic methods. The npes group is more labile towards DBU cleavage than the corresponding base‐protecting 2‐(4‐nitrophenyl)ethyl (npe) and 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which is of great synthetic potential.
Intermediacy of Proton‐Bound Dimers and Ion/Dipole Complexes in the Unimolecular Decompositions of Dialkyl‐Peroxide Radical Cations: Evidence for a coupled proton and hydrogen‐atom transfer
Authors: Schalley Christoph A. , Schröder Detlef , Schwarz Helmut
Published: December 2004

The unimolecular fragmentation reactions of the radical cations of diethyl, diisopropyl, dipropyl, isopropyl propyl, and di(tert‐butyl) peroxide have been investigated by mass spectrometric and isotopic labeling techniques. Two competing pathways for unimolecular decomposition in the μs time regime (metastable ions) are observed: i) A combination of an α‐CC bond cleavage and a H migration gives rise to proton‐bound dimers of two ketone or aldehyde molecules. ii) Ion/dipole complexes of alkyl cations and alkylperoxy radicals are generated by C–O bond cleavage. These complexes either exhibit direct losses of alkylperoxy radicals, or they rearrange via a coupled proton and H‐atom transfer, this sequence of unprecedented isomerizations is completed by losses of alkyl radicals. Collisional activation experiments confirm that the ionic products of the latter process correspond to RR′COOH+; these ions can be regarded as protonated carbonyl oxides. In addition, we observe the elimination of alkenes leading to hydroperoxide radical cations and the expulsion of HO radicals. The latter process implies a CC bond formation step between the two alkyl fragments leading to higher alkyl cations.
Reactions of Enone Ethylene Ketals with Methyl Diazomalonate/Bis(acetylacetonato)copper(II)
Authors: Sezer özkan , Daut Ayşe , Anaç Olcay
Published: December 2004

Several cyclic and acyclic enones and their ethylene ketals/acetals were reacted with dimethyl diazomalonate under bis(acetylacetonato)copper(II) catalysis. Cyclohex‐2‐en‐1‐one (1) yielded only C–H insertion products 2 and 3, whereas but‐3‐en‐2‐one gave a cyclopropane albeit in very low yield. The ethylene ketals 6 of cyclopent‐2‐en‐1‐one and cyclohex‐2‐en‐1‐one gave the corresponding cyclopropanes 7, which were in turn cleaved to the ketones 8. The acetals 9 and 10 of crotonaldehyde ((E)‐but‐2‐enal) and cinnamaldehyde ((E)‐3‐phenylprop‐2‐enal), respectively, yielded C–O insertion and [2,3]‐sigmatropic rearrangement products 11b, c and 12b, c, as well as cyclopropanes 11a and 11b, all of which are polyfunctional and synthetically useful compounds.
Leucascandrolide A, a New Type of Macrolide: The first powerfully bioactive metabolite of calcareous sponges (Leucascandra caveolata, a new genus from the coral sea)
Authors: D'Ambrosio Michele , Guerriero Antonio , Pietra Francesco , Debitus Cécile
Published: December 2004

Leucascandrolide A ((+)‐1), a doubly O‐bridged 18‐membered macrolide of a new type, i.e., showing little C1‐branching vs. extensive 1,3‐dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)‐1 gave the methyl ester 3, derived from the side chain, and the 5‐hydroxy derivative (+)‐2, derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)‐2 showed scattered Δδ = (δ(S) − δ(R)) data. However, inversion of the configuration at C(5) led, via ketone (+)‐6, to the less encumbered 5‐equatorial hydroxy derivative (+)‐7, whose MTPA esters 8 and 9 gave consistent Δδ data, allowing the assignment of the absolute configuration of (+)‐7, and hence of (+)‐1. The structural novelty of (+)‐1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2‐aminoimidazoles.
Gas‐Phase Reactions of Aliphatic Alcohols with ‘Bare’ FeO+
Authors: Schröder Detlef , Wesendrup Ralf , Schalley Christoph A. , Zummack Waltraud , Schwarz Helmut
Published: December 2004

Ion/molecule reactions of ‘bare’ FeO+ with linear and branched aliphatic alcohols have been examined by Fourier‐transform ion‐cyclotron resonance mass spectrometry. Depending on the chain length of the alcohol, three different types of reactions can be distinguished: (i) Oxidation of the alcohols in the α‐positions, to yield the corresponding carbonyl‐Fe+ complexes, involves an initial OH bond activation of the alcohol resulting in the formation of ROFe+OH as the central intermediate. (ii) The formation of Fe(OH), concomitant by loss of the corresponding neutral alkenes, competes with the generation of neutral OFeOH and a carbocation R+. These couples point to the existence of an intracomplex acid‐base equilibrium and are connected with each other by a proton transfer from either acid to the other, e.g. i‐C3H + OFeOH⇄C3H6 + Fe(OH). The process is driven by the Lewis acidity of FeO+ and starts with the abstraction of a hydroxide anion from the alcohol. (iii) For longer alcohols, e.g. pentanol, functionalization of non‐activated CH bonds which are remote from the O functionality is observed. Here, the OH group of the alcohol serves as an anchor, which directs the reactive metal‐oxide cation toward a particular site of the hydrocarbon chain.