CONFORMATIONALLY CONSTRAINED AMINO-ACIDS - SYNTHESIS AND OPTICAL RESOLUTION OF 3-SUBSTITUTED PROLINE DERIVATIVES

被引:88
作者
CHUNG, JYL
WASICAK, JT
ARNOLD, WA
MAY, CS
NADZAN, AM
HOLLADAY, MW
机构
[1] Neuroscience Research Division, Pharmaceutical Discovery, Abbott Laboratories, Illinois 60064, Abbott Park
关键词
D O I
10.1021/jo00288a045
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The literature route to racemic cis- and trans-3-substituted prolines starting from acetamidomalonate and α,β-unsaturated aldehydes has been refined and applied to the synthesis of 3-phenyl- and 3-n-propylproline. A key improvement in the sequence was the acid-catalyzed silane reduction of the initial hydroxylactam Michael adduct 2, which allowed subsequent transformations to proceed cleanly and in high yield. Both the N- and 3-substitutents were found to have an effect on selectivity in the saponification of trans-3-substituted proline esters in the presence of the corresponding cis esters. The trans isomers in each series were resolved via the diastereomeric (S)-α-methylbenzylamides, and the absolute configurations of the resulting pure optical isomers were assigned. © 1990, American Chemical Society. All rights reserved.
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页码:270 / 275
页数:6
相关论文
共 15 条
[1]   INFERENCES ABOUT THE CONFORMATION OF SOMATOSTATIN AT A BIOLOGIC RECEPTOR BASED ON NMR-STUDIES [J].
ARISON, BH ;
HIRSCHMANN, R ;
VEBER, DF .
BIOORGANIC CHEMISTRY, 1978, 7 (04) :447-451
[2]   N-METHYLATION OF AMIDES, LACTAMS, AND UREAS [J].
AUERBACH, J ;
ZAMORE, M ;
WEINREB, SM .
JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (04) :725-726
[3]   SYNTHESIS OF ENANTIOMERICALLY AND DIASTEREOISOMERICALLY PURE SUBSTITUTED PROLINES VIA CONDENSATION OF GLYCINE WITH OLEFINS ACTIVATED BY A CARBONYL GROUP [J].
BELOKON, YN ;
BULYCHEV, AG ;
PAVLOV, VA ;
FEDOROVA, EB ;
TSYRYAPKIN, VA ;
BAKHMUTOV, VA ;
BELIKOV, VM .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1988, (08) :2075-2083
[4]   ABSOLUTE-CONFIGURATION OF 3-PHENYLPYRROLIDINE [J].
BETTONI, G ;
CELLUCCI, C ;
TORTORELLA, V .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1976, 13 (05) :1053-1055
[5]   MODIFIED PROLINE SYNTHESIS [J].
COX, DA ;
MAUGER, AB ;
JOHNSON, AW .
JOURNAL OF THE CHEMICAL SOCIETY, 1964, (DEC) :5024-&
[6]   ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES [J].
DALE, JA ;
DULL, DL ;
MOSHER, HS .
JOURNAL OF ORGANIC CHEMISTRY, 1969, 34 (09) :2543-&
[7]  
DELANEY NG, 1982, INT J PEPT PROT RES, V19, P543
[8]  
HASHIMOTO M, 1986, CHEM LETT, V893
[9]  
HOLLADAY MW, UNPUB
[10]  
HOLLOSI M, 1977, INT J PEPT PROT RES, V10, P286