SYNTHESIS AND CHARACTERIZATION OF AZA ANALOG INHIBITORS OF SQUALENE AND GERANYLGERANYL DIPHOSPHATE SYNTHASES

被引：54

作者：

STEIGER, A ^{[1
]}

PYUN, HJ ^{[1
]}

COATES, RM ^{[1
]}

机构：

[1] UNIV ILLINOIS, DEPT CHEM, 1209 W CALIF ST, URBANA, IL 61801 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1992年 / 57卷 / 12期

关键词：

D O I：

10.1021/jo00038a038

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

One-carbon homologation of geranyl and farnesyl chlorides to secondary N-methylamines (12 and 17) via alpha-lithioformamidine alkylations followed by N-alkylation with bromoacetate esters afforded alpha-(homogeranylamino)-and alpha-(homofarnesylamino)acetates 13 and 18. After alpha-farnesylation of 13, hydride reductions gave branched and straight-chain tertiary beta-amino alcohols 15 and 19. The diphosphate derivatives (7 and 8) of 15 and 19 prepared by SN2 displacements may be regarded as "aza analogs" of plausible carbocation intermediates (5 and 6) in the biosynthesis of squalene and geranylgeranyl diphosphate since, in preliminary collaborative evaluations, they inhibit the respective synthase enzymes at micromolar concentrations.

引用

页码：3444 / 3449

页数：6

共 52 条

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