A practical and scaleable total synthesis of the jaborandi alkaloid (+)-pilocarpine

被引：20

作者：

Davies, Stephen G. ^{[1
]}

Roberts, Paul M. ^{[1
]}

Stephenson, Peter T. ^{[1
]}

Storr, Helen R. ^{[1
]}

Thomson, James E. ^{[1
]}

机构：

[1] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England

来源：

TETRAHEDRON | 2009年 / 65卷 / 39期

关键词：

Jaborandi alkalids; Pilocarpine; Isopilocarpine; Pilosinine; BIFUNCTIONAL CHIRAL SYNTHONS; FORMAL SYNTHESIS; CHIROSPECIFIC SYNTHESIS; BIOCHEMICAL METHODS; PILOCARPINE; ANALOGS; ANNOUNCEMENT; DERIVATIVES; STIMULANTS; PURITY;

D O I：

10.1016/j.tet.2009.07.010

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The total synthesis of (+)-pilocarpine (as its nitrate salt) has been achieved in nine steps and 30% overall yield starting from racemic 2-(2',2'-dimethoxyethyl)propane-1,3-diol, which was desymmetrised via all enzymatic protocol. A high yielding synthesis of a key alpha-ethylidene lactone precursor has been developed, which involves the palladium-catalysed decarboxylation/carbonylation of a 1,3-dioxan-2-one for formation or the gamma-butyrolactone ring. Subsequent hydrogenation of the alpha-ethylidene lactone introduces the C(3)-stereochemistry to give a 72 28 mixture of (+)-pilocarpine and (+)-isopilocarpine, which are readily separable via recrystallisation of the (-)-pilocarpine nitrate salt (C) 2009 Elsevier Ltd All rights reserved

引用

页码：8283 / 8296

页数：14

共 65 条

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