MULTIGRAM LIPASE-CATALYZED ENANTIOSELECTIVE ACYLATION IN THE SYNTHESIS OF THE 4 STEREOISOMERS OF A NEW BIOLOGICALLY-ACTIVE ALPHA-ARYL-4-PIPERIDINEMETHANOL DERIVATIVE

被引：29

作者：

NIEDUZAK, TR ^{[1
]}

MARGOLIN, AL ^{[1
]}

机构：

[1] MERRELL DOW RES INST, INDIANAPOLIS, IN 46268 USA

来源：

TETRAHEDRON-ASYMMETRY | 1991年 / 2卷 / 02期

关键词：

D O I：

10.1016/S0957-4166(00)80531-5

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

The four stereoisomers of the novel non-narcotic analgesic 1-[2-(4-fluorophenyl)-2-hydroxethyl]-4-[(4-fluorophenyl)hydroxymethyl)-piperidine 1 were synthesized in a convergent manner from chiral precursors 2 and 3. Optical resolution via enantioselective acylation in organic media, catalyzed by a lipase from Pseudomonas sp., was utilized in the preparation of 2 and 3 on a multigram scale with high enantiomeric purity (less-than-or-equal-to 97% ee).

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页码：113 / 122

页数：10

相关论文

共 24 条

[1] STEREOCHEMISTRY - A SOURCE OF PROBLEMS IN MEDICINAL CHEMISTRY [J].

ARIENS, EJ .

MEDICINAL RESEARCH REVIEWS, 1986, 6 (04) :451-466

[2] STEREOSELECTIVITY OF BIOACTIVE XENOBIOTICS - A PRE-PASTEUR ATTITUDE IN MEDICINAL CHEMISTRY, PHARMACOKINETICS AND CLINICAL-PHARMACOLOGY [J].

ARIENS, EJ ;

WUIS, EW ;

VERINGA, EJ .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (01) :9-18

[3] LIPASE-CATALYZED IRREVERSIBLE TRANSESTERIFICATION USING ENOL ESTERS - RESOLUTION OF PROSTAGLANDIN SYNTHONS 4-HYDROXY-2-ALKYL-2-CYCLOPENTENONES AND INVERSION OF THE 4S ENANTIOMER TO THE 4R ENANTIOMER [J].

BABIAK, KA ;

NG, JS ;

DYGOS, JH ;

WEYKER, CL ;

WANG, YF ;

WONG, CH .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (10) :3377-3381

[4] A CHEMOENZYMATIC SYNTHESIS OF (+)-CASTANOSPERMINE [J].

BHIDE, R ;

MORTEZAEI, R ;

SCILIMATI, A ;

SIH, CJ .

TETRAHEDRON LETTERS, 1990, 31 (34) :4827-4830

[5]

CARR AA, Patent No. 325268

[6] LIPASE-CATALYZED TRANSESTERIFICATION IN THE SYNTHESIS OF A NEW CHIRAL UNLABELED AND C-14-LABELED SEROTONIN UPTAKE INHIBITOR [J].

CREGGE, RJ ;

WAGNER, ER ;

FREEDMAN, J ;

MARGOLIN, AL .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (14) :4237-4238

[7] NUCLEAR MAGNETIC-RESONANCE ENANTIOMER REAGENTS - CONFIGURATIONAL CORRELATIONS VIA NUCLEAR MAGNETIC-RESONANCE CHEMICAL-SHIFTS OF DIASTEREOMERIC MANDELATE, O-METHYLMANDELATE, AND ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETATE (MTPA) ESTERS [J].

DALE, JA ;

MOSHER, HS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1973, 95 (02) :512-519

[8] CHEMOENZYMATIC SYNTHESIS OF CHIRAL ISOXAZOLE DERIVATIVES [J].

DEAMICI, M ;

DEMICHELI, C ;

CARREA, G ;

SPEZIA, S .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (11) :2646-2650

[9] THE FDA PERSPECTIVE ON THE DEVELOPMENT OF STEREOISOMERS [J].

DECAMP, WH .

CHIRALITY, 1989, 1 (01) :2-6

[10]

DELINCK DL, 1990, UNPUB TETRAHEDRON LE