HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Yoshio Ban's Special Issues, Vol. 42, No. 2, 1996
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■ Asymmetric Dialkylation of Chiral 2-Benzazepine Formamidines
A. I. Meyers and Richard Hutchings
*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.
Abstract
Repeated metallation and alkylation of an (S)-(+)-tertleucinol derived 2,3,4,5-tetrahydro-1H-2-benzazepine formamidine leads to the corresponding 1,1 -dialkyl-2-benzaepines in good yields and with excellent enantioselectivities.
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■ Biotransformation of Dibenzylbutanolides by Peroxidase Enzymes. Routes to the Podophyllotoxin Family.
James P. Kutney, Xinyao Du, Rajina Naidu, Nikolay M. Stoynov, and Masumi Takemoto
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver B.C., V6T 1Z1, Canada
Abstract
In continuing studies on enzyme-catalyzed cyclization of synthetic dibenzylbutanolides to members of the podophyllotoxin family, experiments which involve the biotransformation of such synthetic substrates with horseradish peroxidase and with enzymes produced by the cell culture of Nicotiana sylvestris are presented. Cyclization of synthetic 3 to the desired 5 proceeds efficiently with purified horseradish peroxidase enzyme but not with the acetone powder. A much preferred route to 5, in gram scale synthesis, involves the biotransfonnation of 3 with the enzymes produced by the cell culture of Nicotiana sylvestris. This stable cell line, when grown in bioreactors, produces sufficient quantities of enzyme for efficient multi-gram synthesis in short time incubations (5-30 min). The application of this methodology for production of podophyllotoxins utilized as starting materials in etoposide synthesis is under study in our laboratory.
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■ A Mild and Rapid Glycosylation Reaction between Pyrimidine Bases and 2-Deoxyribofuranosyl N,N,N',N'-Tetramethylphosphoroamidates
Takamasa Iimori, Hiroshi Kobayashi, Shun-ichi Hashimoto, and Shiro Ikegami*
*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan
Abstract
A trimethylsilyl triflate-mediated coupling reaction to produce protected 2’-deoxynucleosides has been developed by using N,N,N’,N’-tetramethylphosphoroamidate as a leaving group. In this reaction, employment of a 3,4,5-trimethoxybenzoyl group as the 3-hydroxyl protective group in the sugar moiety improved the β-stereoselectivity via a novel 1,3-participation.
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■ The Mechanism of Configuration Retention in the Substitution Reaction of C4-Tosyloxyproline with Lithium Diarylcuprate
Kimiko Hashimoto, Yukio Shima, and Haruhisa Shirahama*
*Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
Abstract
The mechanism of configuration retention during the substitution reaction of C4-tosyloxyproline with lithium diarylcuprate was studied. Among the three possible intermediates (a~c), c has been found to be the origin of the retention mechanism.
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■ Total Synthesis of (-)-Qinghaosu IV (Artemisinin D, Arteannuin D)
Hsing-Jang Liu* and Wen-Lung Yeh
*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Abstract
Starting from (-)-β-pinene (3), a total synthesis of (-)-qinghaosu IV (1) has been accomplished.
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■ Practical Radical Deoxygenation of Erythromycins by Barton Reaction
Tsutomu Sato, Hiroshi Koga, and Koichi Tsuzukli
*Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., 135, 1-Chome Komakado, Gotemba City, shizuoka 412-8513, Japan
Abstract
Practical radical deoxygenation method of erythromycins was established. Macrolide-type motilin receptor agonist GM-665 (1) has been prepared using this method.
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■ One-Step Synthesis of (-)-5-epi-Hydantocidin
Noriyuki Nakajima, Masayuki Kirihara, Miyoko Matsumoto, Masaru Hashimoto, Tadashi Katoh, and Shiro Terashima
*Sagami Central Research Center, Nishi-Ohnuma, Sagamihara, Kanagawa 229-0012, Japan
Abstract
One-step synthesis of (-)-5-epi-hydanrocidin was achieved by heating a mixture of D-isoascorbic acid and urea without solvent. Studies on N,O-spiroketal formation and epimerization between (+)-hydantocidin and (-)-5-epi-hydantocidin were also carried out to explore some mechanistic aspects of the obtained results.
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■ Syntheses of Proposed Structure of Pseudodistomin A Triacetate and Its Regioisomers on Dienyl Side-Chain
Toshiko Kiguchi, Yoko Yuumoto, Ichiya Ninomiya, and Takeaki Naito
*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Abstract
The amino alcohol (5) was employed as a common starting compound for the synthesis of the piperidines (1b), (14), and (16) with three isomeric tridecadienyl side-chains. The spectral data of the 6’E,8’Z-diene (14) are closely resembled with those of natural pseudodistomin A triacetate.
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■ Novel Indole-Ring Construction Method for the Synthesis of 2-Trifluoromethylidoles
Kazuyuki Miyashita, Katsutoshi Tsuchiya, Katsunori Kondoh, Hideto Miyabe, and Takeshi Imanishi
*Faculty of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
Novel indole-ring construction method, which is particularly effective for the synthesis of 2-perfluoroalkylindoles, and introduction of a cyanomethyl group at C-3 of 2-perfluoroalkylindoles by means of the Mannich reaction are described.
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■ Novel Nonprostanoid Prostacyclin (PGI2) Mimetics with Heterocyclic Moiety
Yuuki Nagao, Kanji Takahashi, Kazuhiko Torisu, Kigen Kondo, and Nobuyuki Hamanaka
*Minase research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, Osaka 618, Japan
Abstract
Structural modification of [2-(2-benzhydryloxyiminopentyl)-1,2,3,4-tetrahydro-5-naphthyloxy]acetic acid (4), previously identified as a PGI2 agonist without a PG skeleton, was examined. Conversion of the oxime moiety in 4 to the pyrazole led to [2-(4-benzhydrylpylazoyl)methyl-1,2,3,4-tetrahydro-5-naphthyloxy]acetic acid (34) which strongly inhibited ADP-induced aggregation of human platelets in vitro.
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■ A Microwave-accelerated Intramolecular Diels-Alder Reaction. Approach to Compactin
Kazuhiko Takatori, Kazushi Hasegawa, Satoshi Narai, and Masahiro Kajiwara
*Department of Medicinal Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
Microwave irradiation drastically accelerated the intramolecular Diels-Alder reactions of 5a-c as compared with conventional heating. The resulting carboxylic acid (7c) was converted, to the decalin unit (2a), which is a possible key intermediate for synthesis of compactin (1).
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■ Versatile Synthesis of Enantiomerically Pure trans-2,5-Disubstituted Pyrrolidines
Michael Dockner, N. André Sasaki, and Pierre Potier
*Institut des Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
Enantiomerically pure trans-(2S,5S)-2,5-disubstituted pyrrolidine was synthesized starting from the versatile chiral synthon (R)-(8) and chiral 2,3-O-isopropylideneglycerol triflate (S)-(9).
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■ Cycloaddition Reactions of Methacryloyl Isocyanate with Arylideneamines
Otohiko Tsuge, Taizo Hatta, Ryuzo Mizuguchi, Toshiyuki Kobayashi, and Ryouichi Kanzaki
*Department of Industrial Chemistry, Kumamoto Institute of Technology, 4-22-1, Ikeda, Kumamoto, 860 Japan
Abstract
Arylideneamines (1) added to the acyl isocyanato moiety of methacryloyl isocyanate (MAI) to produce the corresponding [4 + 2] cycloadducts, 2H-1,3,5-oxadiazin-4(3H-ones (2). It has been clarified that even at low temperature the cycloadducts (2) partially dissociate to two original substrates, MAI and 1, in solution on the basis of VT-nmr spectroscopy.
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■ Dirhodium(II) Tetrakis[3(S)-phthalimido-2-piperidinonate]: A Novel Dirhodium(II) Carboxamidate Catalyst for Asymmetric Cyclopropanation
Nobuhide Watanabe, Hideo Matsuda, Harumi Kuribayashi, and Shun-ichi Hashimoto
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Dirhodium(II) tetrakis[3(S)-phthalimido-2-piperidinonate] catalyzes cyclopropanation of α-methylstyrene with d-menthyl diazoacetate to give d-menthyl menthyl (1S,2S)-2-methyl-2-phenylcyclopropanecarboxylate 90% de.
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■ Enantioselective Allylic Alkylation and Amination Catalyzed by a Chiral P/N Ligand-Palladium Complex
Hideki Kubota and Kenji Koga
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
The phosphorus-containing C2-symmetric chiral amine ligand (3) has been found to be highly effective for enantioselective allylic substitution catalyzed by palladium complex. A high level of enantioselectivity has been achieved in the reaction of racemic 1,3-diphenyl-2-propenyl acetate with various C-nucleophiles (>95% e.e.) and N-nucleophiles (84-92% e.e.).
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■ Aprotic Chloride and Bromide-promoted Alkyne-Iminium Ion Cyclizations
Yoshinori Murata and Larry E. Overman
*Department of Chemistry, University of California, Irvine, California 92717-2025, U.S.A.
Abstract
The title cyclizations of 4-alkynyl- and 3-alkynyl-N-(methoxymethyl)-mines occur under milder conditions, and in the case of chloride in higher yields, than direct cyclizations of the corresponding secondary amine with formaldehyde and a halide salt.
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■ Withanis somnifera - a Source of Exotic Withanolides
M. Iqbal Choudhary*, Samina Abbas, S. Arshad Jamal, and Atta-ur-Rahman*
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
Withania somnifera has yielded three new withanolides somnifericin (1),2,3-dehydrosomnifericin(2), and withaoxylactone (3).
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■ Carbometalation of Cyclopropenes. Seteroselective Synthesis of Divinyl Ketones via 1,5-Hydrogen Migration Reaction of Vunylcyclopropanes
Katsumi Kubota, Masahiko Isaka, and Eiichi Nakamura
*Department of Chemistry, Tokyo Instituteof Technology, Meguro-ku, Tokyo 152-8552, Japan
Abstract
Stereoselective addition of a vinyl cuprate reagent to a cyclopropenone acetal (2) followed by in situ electrophilic trapping with an alkylating agent affords a cis-1-alkyl-2-vinylcyclopropanone acetal (3), which then undergoes thermal 1,5-hydrogen migration reaction to give the acetal of a Z,E-dienone (4) in 70-90% overall yield. Hydrolysis under mild acidic conditions affords the corresponding dienone or trienone (5) in high yield.
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■ Synthetic Studies of Novel 5-Azacarbapenems
Kuniyuki Oda, Takao Nakano, Hiroshi Morimoto, and Norio Takamura
*Organic Chemistry Research Laboratory, Tanabe Seiyaku Co.Ltd., 2-2-50, Kawagishi, Toddda, Saitama 335-8505, Japan
Abstract
1,2-Diazetidiiones were prepared from (2R, 3R)-epoxybutanoic acid via acidic one-pot deprotection-cyclization reaction and converted to the novel 5-azacarbapenams by an intramolecular Michael cyclization reaction.
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■ Neighboring Assistance of a Hydroxyl Group on Manganese Dioxide Oxidation of Benzyl Alcohols to Lactones
Katsuya Endo, Hiroyasu Takahashi, and Minako Aihara
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
o-Hydroxymethylbenzyl alcohol and o-hydroxyethylbenzyl alcohols have been converted to phthalide and dihydroisocoumarins, very easily and in high yields, by oxidation with non-activated manganese dioxide. In contrast, the reaction of o-hydroxypropylbenzyl alcohol stopped at the aldehyde level, and afforded only a small amount of the corresponding lactone under the same condition. This implies that the first oxidation product, a benzaldehyde, could be oxidized further via a hemiacetal, but the second oxidation to lactone is very much dependent on the ability of stable intramolecular hemiacetal formation, and not on the intermolecular mode at all.
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■ New Synthesis of Quinoxaline Derivatives Based on Palladium Catalyzed Oligomerization of 1,2-Diisocyanoarenes
Yoshihiko Ito, Yutaka Kojima, Michinori Suginome, and Masahiro Murakami
*Departmene of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan
Abstract
Various 2,3-disubstituted quinoxaline derivatives were synthesized from monomeric and oligomeric (3-substituted quinoxaline-2-yl)palladium(ll)s, which were prepared by the reaction of o-diisocyanoarenes with trans-bromo(methyl)bis(phosphine)palladium(ll).
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■ Hydrolysis of Isomeric Tricyclic Orthoesters and AM1 Molecular Modelling of the Reaction Pathway Further Evidence for Stereoselectronic Control
Pierre Deslongchamps, Yves L. Dory, and Shigui Li
*Department of Chemistry, Faculty of Sciences, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1, Canada
Abstract
Two tricyclic orthoesters and three other onhoesters have been submitted to acid hydrolysis conditions to yield mixtures of lactones and esters. The ratios of different products have been rationalized in terms of stereoelectronic, steric and entropy effects at the various steps. A quantitative AM1 investigation has been carried out, starting from the only tricyclic hemi-orthoester intermediate of the whole system, in order to compare the hydrolysis routes leading to the kinetic and thermodynamic lactone products.
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■ tert-Butylcyclopentane Derivatives. Part 8. Synthesis of tert-Butylcyclopentane-fused Pyrimidin-4-ones
Zsolt Szakonyi, Ferenc Fülöp, Gábor Bernáth, and Pál Sohár
*Institute of Pharmaceutical Chemistry, Albert Szent-Györgyi Medical University, H-6701 Szeged, Eötv¨øs u.6., Hungary
Abstract
In the reactions of ethyl (1R*,2S*,4S*)-2-amino-4-tert-butyl-1-cyclopentanecarboxylate (4) or (1R*,3S*,5S*)-3-tert-butyl-6-azabicyclo[3.2.0]heptan-7-one (2) or (1R*,2S*,4S*)-2-amino-4-tert-butyl-1-cyclopentanecarboxamide (6) with imidates or triethyl orthobenzoate, tert-butylcyclopentane-fused dihydropyrimidin-4-ones (7a-e) were prepared. The azetidinone (2) with lactim ethers furnished pyrrolo-, pyrido- and azepino[1,2-a]pyrimidin-4-ones (8-10) in ringenlargement reactions. Ethyl (1R*,2S*,4S*)-2-amino-4-tert-butyl-1-cyclopentanecarboxylate (4) and ethyl (1R*,2S*,4S*)-2-benzylamino-4-tert-butyl-1-cyclopentanecarboxylate (5) and potassium cyanate or phenyl isocyanate or potassium thiocyanate or phenyl isothiocyanate, yielded pyrimidine-2,4-diones or 2-thioxopyrimidin-4-ones (11-22).
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■ Tandem Stereoselective Conjugate Additions to α,β-Unsaturated Oxazolines
Nathalie Dahuron, Nicole Langlois, Angèle Chiaroni, and Claude Riche
*Institut des Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
Tandem stereoselective conjugate additions to two molecules of activated α,β-unsaturated oxazolines have led to substituted 2,4-bis-(4-phenyl-4,5-dihydrooxazol-2-yl)-cyclopent-1-enylamines.Their general structure was deduced from spectral data and confirmed by X-ray analysis.
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■ Synthesis and Biological Evaluation of Sodium 2β-[(2,5-Dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)sulfonylmethyl]-2α-methylpenam-3α-carboxylate 1,1-Dioxide
Eduardo L. Setti, Oludotun A. Phillips, Andhe V. N. Reddy, Chieko Kunugita, Akio Hyodo, Ronald G. Micetich, and Samarendra N. Maiti
*SynPhar Laboratories Inc., 4290-91A Street, Edmonton, Alberta, T6E 5V2, Canada
Abstract
A new β-lactamase inhibitor, sodium 2β-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)sulfonymethyl]-2α-methylpenam-3α-carboxylate 1,1-dioxide (3). was synthesized. The compound (3) had excellent invitro inhibitory activity except against cephalosporinase. In combination with ampicillin, piperacillin and ceftazidime, its synergistic effects was inferior to tazobactam, thus suggesting poor penetration through the bacterial cell wall.
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■ β-Lactamase Inhibitors: Synthesis and in vitro Evaluation of 6-[(1-Substituted1,2,3-Triazol-4-yl)methylene]penicillanic Acid Sulfones
Paul Eby, Maxwell D. Cummings, Oludotun A. Phillips, David P. Czajkowski, Maya P. Singh, Paul Spevak, Ronald G. Micetich, and Samarendra N. Maiti
*SynPhar Laboratories Inc., 4290-91A Street, Edmonton, Alberta, T6E 5V2, Canada
Abstract
A series of 6-[(1-substituted 1,2,3-triazol-4-yl)methylene]penicillani acid sulfones were synthesized and tested for β-lactamase inhibitory activity. The (6Z)-isomers were over 100 times more potent than the (6E)-isomers against cell-free β-lactamases and were synergistic with ampicillin against a variety of β-lactamase producing bacteria.
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■ De Novo Synthesis of Racemic Altronolactam and Arabinonolactam Azasugars
Théophile Tschamber, Elsa-Maria Rodriguez-Perez, Patrick Wolf, and Jacques Streith
*Ecole Nationale Supérieure de Chimie de Mulhouse, Université de Haute Alsace, 3, Rue Alfred Werner 68093 Mulhouse Cedez, France
Abstract
Starting from the known peracetylated piperidinose derivatives (7a) and (7b), the corresponding altrono- and arabinon- lactams (4) and (5) were obtained in a straightforward way. A selective two-step hydrolysis of the anomeric acetoxy groups gave the free hydroxyls (8a) and (8b) which were oxidised to the β-lactams (9a) and (9b), respectively. Deprotection of these latter compounds led to the target molecules.
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■ Diels-Alder Reaction of the Dihydropyridinones V: Approach to the Ircinal B Core
Yasuhiro Torisawa, Mohamed Ayman Ali, Fabrice Tavet, Akiko Kageyama, Maki Aikawa, Naoko Fukui, Tohru Hino, and Masako Nakagawa*
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Thermal and high-pressure Diels-Alder reaction of the suitably assembled dihydropyridinones afforded the hydroisoquinoline derivatives, which were transformed to the key intermediates for the ABC substructure of ircinal B.
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■ Synthesis of Fused Pyrimidinones by Reaction of Aminoarenecarboxamide with Esters; Preparation of Pyrrolo[2,3-d]-, Thieno[2,3-d]-, Isoxazolo[5,4-d]-, and 1,2,3-Triazolo[4,5-d]-pyrimidinones, and Quinazolones
Akira Miyashita, Katsuhiro Fujimoto, Tomomi Okada, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Several fused pyrimidinones were synthesized by reaction of aminoarenecarboxamide with esters in moderate to good yields. In the presence of sodium ethoxide, treatments of 2-amino-1-phenyl-3-pyrrolecarboxamide(4,5, and 6), 2-amino-3-thiophenecarboxamide (14), 3-amino-4-isoxazolecarboxamide (10 and 11), 4-amino-1,2,3-triazole-5-carboxamide (16), and o-aminobenzamide (18) with esters (3) such as ethyl formate (3a) and ethyl acetate (3b) led to the corresponding pyrrolo[2,3-d]- (7,8, and 9), and thieno[2,3-d]pyrimidin-4(3H)-ones (15), isoxazolo[5,4-d]pyrimidin-4(5H)-ones (12 and 13), 1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-ones (17), and 4(3H)-quinazolones (19), respectively.
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■ Ring Opening of Optically Active cis-Disubstituted Aziridino Alcohols: An Enantiodivergent Synthesis of Functionalized Amino Alcohol Derivatives
Kaoru Fuji, Takeo Kawabata, Yoshimitsu Kiryu, and Yukio Sugiura
*Institute for Chemistry, Kyoto University, Uji, Kyoto 611-0011, Japan
Abstract
Ring-opening reactions of optically active cis-disuhstituted aziridino alcohols have been investigated. Regio- and stereo-selective ring opening took place with internal and external nucleophiles. Unusual amino acids derivatives (14) and (15), the key synthetic intermediates for bestatin and related peptides, have been prepared.