ENZYMATIC KINETIC SEPARATION OF STEREOISOMERIC MACROCYCLIC LACTONE DERIVATIVES, 7-ALPHA,BETA-O-ACYL TRANS-ZEARALENOLS AND 7-ALPHA,BETA-O-ACYL ZEARANOLS

被引:14
作者
GELO, M
SUNJIC, V
机构
[1] Ruder Bošković Institute, 41001 Zagreb
关键词
LIPASES; DIASTEREOSELECTIVITY AND SITE-SELECTIVITY OF HYDROLYSIS; 7-ALPHA; BETA-ORTHO-ACYL DERIVATIVES OF RESORCYCLIC ACID MACROCYCLIC LACTONES;
D O I
10.1016/S0040-4020(01)88241-7
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Diastereomeric mixtures of resorcylic acid macrocyclic lactones, 7-alpha, beta-O-acyl zearalenols (1,2 and 3,4, full name: trans-3,4,5,6,9,10-octahydro-14,16-dihydroxy-7-acyloxy-3-methyl 1H-2-benzoxacyclotetradecin-1-ones (3S,7S or 3S,7R)), and 7-alpha, beta-acyl zearanols (5,6 and 7,8, full name: 3,4,5,6,9,10,11,12-decahydro-14,16-dihydroxy-7-acyloxy-3-methyl-1H-2-benzoxacyclotetradecin-1-ones (3S,7S or 3S,7R)) are hydrolyzed by lipases. Kinetic separation affords 7-beta-alcohols with complete site-selectivity and nearly complete diastereoselectivity. Among lipases examined, those from Pseudomonas sp., Pseudomonas fluorescens and Candida cylindracea exhibit the broadest substrate specificity. In all cases 7-beta-alcohols are major products, diastereomeric excess (d.e. in %, determined by HPLC) approaches 100% for 1,2, 80% for 3,4, and varies between 10% and 90% for 5,6 and 7,8, respectively. Faster and less stereoselective hydrolysis is observed for 7-alpha, beta-O-chloroacetyl derivatives 3,4 and 7,8 as compared with acetyl derivatives 1,2 and 5,6. The effect of ionic strength and of organic cosolvent on the rate and selectivity is studied. Explanation of stereoeslectivity of this enzymatic reaction is based on die conformational properties of macrocyclic ring around the chiral acyloxymethine center C(7). Perturbation by the local helical arrangement of die two trimethylenic side-chains attached to this center renders 7-beta-O-acyl diastereomers much more reactive counterparts.
引用
收藏
页码:6511 / 6520
页数:10
相关论文
共 41 条
[1]   A SERINE PROTEASE TRIAD FORMS THE CATALYTIC CENTER OF A TRIACYLGLYCEROL LIPASE [J].
BRADY, L ;
BRZOZOWSKI, AM ;
DEREWENDA, ZS ;
DODSON, E ;
DODSON, G ;
TOLLEY, S ;
TURKENBURG, JP ;
CHRISTIANSEN, L ;
HUGEJENSEN, B ;
NORSKOV, L ;
THIM, L ;
MENGE, U .
NATURE, 1990, 343 (6260) :767-770
[2]  
BROWN RG, 1983, ANABOLIC AGENTS ANIM, P155
[3]   ENANTIOSELECTIVE ESTERIFICATIONS OF UNSATURATED ALCOHOLS MEDIATED BY A LIPASE PREPARED FROM PSEUDOMONAS SP [J].
BURGESS, K ;
JENNINGS, LD .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (16) :6129-6139
[4]   CONTRIBUTIONS OF STERIC, ELECTRICAL, AND POLARIZABILITY EFFECTS IN ENANTIOSELECTIVE HYDROLYZES WITH RHIZOPUS-NIGRICANS - A QUANTITATIVE-ANALYSIS [J].
CHARTON, M ;
ZIFFER, H .
JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (12) :2400-2403
[5]   PREPARATION OF OPTICALLY-ACTIVE SECONDARY ALCOHOLS BY COMBINATION OF ENZYMATIC-HYDROLYSIS AND CHEMICAL TRANSFORMATION [J].
DANDA, H ;
NAGATOMI, T ;
MAEHARA, A ;
UMEMURA, T .
TETRAHEDRON, 1991, 47 (41) :8701-8716
[6]   THE SYNTHESIS OF CHIRAL ISOPROPYLIDENE DERIVATIVES OF 1,2,3-CYCLOHEXANETRIOLS BY ENZYMATIC DIFFERENTIATION [J].
DUMORTIER, L ;
VANDEREYCKEN, J ;
VANDEWALLE, M .
TETRAHEDRON LETTERS, 1989, 30 (24) :3201-3204
[7]  
EHRLER J, 1990, LIEBIGS ANN CHEM, P379
[8]  
FOLSCHE E, 1990, J ORG CHEM, V55, P1749
[9]  
FOUQUE E, 1989, SYNTHESIS-STUTTGART, P661
[10]   DETERMINATION OF THE CONFORMATION OF E AND Z ZEARALENONE AND THEIR 7-ALPHA-HYDROXY AND 7-BETA-HYDROXY CONGENERS [J].
GELO, M ;
RAZA, Z ;
SUNJIC, V ;
GUO, J ;
SNATZKE, G .
TETRAHEDRON-ASYMMETRY, 1991, 2 (10) :1005-1010