CHIROSPECIFIC SYNTHESIS OF (1S,3R)-1-AMINO-3-(HYDROXYMETHYL)CYCLOPENTANE, PRECURSOR FOR CARBOCYCLIC NUCLEOSIDE SYNTHESIS - DIECKMANN CYCLIZATION WITH AN ALPHA-AMINO-ACID

被引:76
作者
BERGMEIER, SC [1 ]
COBAS, AA [1 ]
RAPOPORT, H [1 ]
机构
[1] UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720
关键词
D O I
10.1021/jo00061a006
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Carbocyclic nucleosides are important isosteres of nucleosides possessing a variety of antiviral and antineoplastic activities. We report here a new method for the chirospecific synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane. This compound is a key precursor for the synthesis of some carbocyclic nucleosides. The method involves (1) an improved synthesis of (S)-2-aminoadipic acid; (2) Dieckmann cyclization of this alpha-amino acid to an aminocyclopentanone; and (3) elaboration of the latter to the target (1S,3R)-l-amino-3-(hydroxymethyl)cyclopentane. The starting (S)-2-aminoadipic acid delta-methyl ester was prepared enantiomerically pure from (S)-aspartic acid in 51% overall yield. Dieckmann condensation converted this amino acid to a (methoxycarbonyl)-cyclopentanone, and reduction of the ketone followed by elimination yielded (S)-3-[N-(9-phenylfluoren-9-yl)amino]-1-(methoxycarbonyl)cyclopentene. Reduction of the double bond gave a mixture of the cis and trans diastereomers. This mixture was converted to a single diastereomer by epimerization and trapping of the cis isomer as (1S,4R)-2-(9-phenylfluoren-9-yl)-2-azabicyclo[2.2.1]heptan-3-one. Hydrolytic cleavage of the lactam followed by reduction gave (IS,3R)-1-amino-3-(hydroxymethyl)-cyclopentane.
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页码:2369 / 2376
页数:8
相关论文
共 56 条
  • [1] [Anonymous], 1991, ORGANIC REACTIONS, DOI 10.1002/0471264180.or040.02
  • [2] SYNTHESIS OF N-BENZYLOXYCARBONYL-L-ALPHA-AMINOADIPIC ACID, ALPHA-BENZYL ESTER
    BALDWIN, JE
    KILLIN, SJ
    ADLINGTON, RM
    SPIEGEL, U
    [J]. TETRAHEDRON, 1988, 44 (09) : 2633 - 2636
  • [3] A SYNTHESIS OF ISOASPARAGINE FROM BETA-BENZYL ASPARTATE
    BENOITON, L
    [J]. CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1962, 40 (03): : 570 - &
  • [4] STEREOSPECIFIC SYNTHESIS OF (-)-CARBOCYCLIC 2',3'-DIDEOXYTHYMIDINE, A POTENTIAL ANTI-AIDS AGENT
    BERES, J
    SAGI, G
    TOMOSKOZI, I
    GRUBER, L
    GULACSI, E
    OTVOS, L
    [J]. TETRAHEDRON LETTERS, 1988, 29 (22) : 2681 - 2684
  • [5] STEREOSPECIFIC SYNTHESIS OF (+)-CARBOCYCLIC 2'-DEOXYADENOSINE - AN IMPROVED PROCEDURE FOR THE PREPARATION OF (+)-(1R,2S,4R)-4-AMINO-2-HYDROXY-1-HYDROXYMETHYLCYCLOPENTANE
    BERES, J
    SAGI, G
    BAITZGACS, E
    TOMOSKOZI, I
    OTVOS, L
    [J]. TETRAHEDRON, 1988, 44 (19) : 6207 - 6216
  • [6] FLUOROCARBOCYCLIC NUCLEOSIDES - SYNTHESIS AND ANTIVIRAL ACTIVITY OF 2'-FLUOROCARBOCYCLIC AND 6'-FLUOROCARBOCYCLIC 2'-DEOXY GUANOSINES
    BORTHWICK, AD
    KIRK, BE
    BIGGADIKE, K
    EXALL, AM
    BUTT, S
    ROBERTS, SM
    KNIGHT, DJ
    COATES, JAV
    RYAN, DM
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (03) : 907 - 914
  • [7] SYNTHESIS OF CHIRAL CARBOCYCLIC NUCLEOSIDES
    BORTHWICK, AD
    BIGGADIKE, K
    [J]. TETRAHEDRON, 1992, 48 (04) : 571 - 623
  • [8] SYNTHESIS AND ENZYMATIC RESOLUTION OF CARBOCYCLIC 2'-ARA-FLUORO-GUANOSINE - A POTENT NEW ANTI-HERPETIC AGENT
    BORTHWICK, AD
    BUTT, S
    BIGGADIKE, K
    EXALL, AM
    ROBERTS, SM
    YOUDS, PM
    KIRK, BE
    BOOTH, BR
    CAMERON, JM
    COX, SW
    MARR, CLP
    SHILL, MD
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1988, (10) : 656 - 658
  • [9] MILD AND SIMPLE BIOMIMETIC CONVERSION OF AMINES TO CARBONYL-COMPOUNDS
    BUCKLEY, TF
    RAPOPORT, H
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1982, 104 (16) : 4446 - 4450
  • [10] CAIRNS TL, 1941, J AM CHEM SOC, V63, P871