An improved synthesis of enantiomerically pure CIP-AS, potent and selective AMPA-kainate receptor agonist

被引：14

作者：

Conti, P ^{[1
]}

Roda, G ^{[1
]}

Negra, FFB ^{[1
]}

机构：

[1] Univ Milan, Ist Chim Farmaceut & Tossicol, I-20131 Milan, Italy

来源：

TETRAHEDRON-ASYMMETRY | 2001年 / 12卷 / 09期

关键词：

D O I：

10.1016/S0957-4166(01)00225-7

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

CIP-AS (-)-2, a chiral amino acid structurally related to glutamic acid, behaves as a potent agonist at the ionotropic AMPA-kainate receptors and was previously prepared in low overall yield through the 1,3-dipolar cycloaddition of ethoxycarbonylformonitrile oxide to N-BOC-3,4-didehydro-(S)-proline methyl ester (-)-6. Herein, we report an alternative strategy based on the cycloaddition of the same dipolarophile to N-(4-methoxybenzyl)-alpha -ethoxycarbonylnitrone 12. The mixture of stereoisomeric 3-ethoxycarbonyl-N-(4-methoxybenzyl)iso prolines 13 was then converted into the corresponding 3-ethoxycarbonyl-Delta (2)-isoxazolinyl prolines by DDQ mediated oxidation. The new strategy yielded the precursor of CIP-AS in satisfactory overall yield and represents an improvement upon the existing procedure in terms of yield and efficiency. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1363 / 1367

页数：5

共 28 条

[1] 1,3-DIPOLAR CYCLOADDITIONS OF ETHOXYCARBONYL-NITRILE BENZYLIMINE, ETOOC C-N+-N- CH2C6H5, AND SYNTHESIS OF BETA-AMINO ACIDS - SYNTHESIS AND REACTIONS OF ETHYL 2-CHLORO-2-ETHOXYACETATE AND 2-CHLORO-2-ETHOXYACETYL CHLORIDE [J].