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Synthesis and muscarinic M(2) subtype antagonistic activity of enantiomeric pairs of 3-demethylhimbacine (3-norhimbacine) and its C(4)-epimer.

Abstract：

:In the course of our studies of the structure-activity relationships of himbacine 1, a potent antagonist of the M(2) subtype of muscarinic receptor, the four title compounds, 2, ent-2, 3, and ent-3, were synthesized with a highly stereoselective intermolecular Diels-Alder reaction of tetrahydroisobenzofuran 4 with achiral furan-2(5H)-one 5 as a key step, followed by simultaneous optical resolution and epimer separation of the racemic intermediates. Among these compounds, 3-demethylhimbacine (3-norhimbacine) 2, bearing an absolute configuration corresponding to that of 1, was found to show more potent muscarinic M(2) subtype receptor binding activity than natural 1.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Takadoi M,Yamaguchi K,Terashima S

doi

10.1016/s0960-894x(02)00695-9

subject

Has Abstract

pub_date

2002-11-18 00:00:00

pages

3271-3

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960894X02006959

journal_volume

12

pub_type

杂志文章

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