First enantiospecific synthesis of a 3,4-dihydroxy-L-glutamic acid [(3S,4S)-DHGA], a new mGluR1 agonist

被引：26

作者：

Dauban, P

de Saint-Fuscien, C

Acher, F

Prézeau, L

Brabet, I

Pin, JP

Dodd, RH ^{[1
]}

机构：

[1] CNRS, Inst Chim Subst Nat, F-91198 Gif Sur Yvette, France

[2] Univ Paris 05, Chim & Biochim Pharmacol & Toxicol Lab, CNRS, UMR 8601, F-75270 Paris, France

[3] CNRS, CCIPE, UPR 9023, F-34094 Montpellier, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(99)00641-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The first synthesis of one of the 4 possible stereoisomers of 3,3-dihydroxy-L-glutamic acid ((3S,4S)-DHGA 3), a natural product of unknown configuration, is described. The synthesis is based on the Lewis acid catalyzed reaction of benzyl alcohol with a D-ribose-derived 2,3-aziridino-gamma-lactone 4-benzyl carboxylate (6). Preliminary pharmacological studies showed that (3S,4S)-3 is an agonist of metabotropic glutamate receptors of type 1 (mGluR1) and a weak antagonist of mGluR4 but has no discernible activity with respect to mGluR2. This activity profile can be rationalized by fitting extended conformations of (3S,4S)-3 in proposed models of each of these receptor subtypes. (C) 2000 Elsevier Science Ltd. All rights reserved.

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页码：129 / 133

页数：5

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