Synthesis of (±)-2R,4R,5S-2-methoxy-4-nitro-5-(2,3,4-trimethoxyphenyl)cyclohexanone and (±)-2R,4S,5R-2-methoxy-5-nitro-4-(2,3,4-trimethoxyphenyl)cyclohexanone as colchicine mimetics

被引：2
|
作者：
Evans, KA [1 ]
Beshah, K [1 ]
Young, DH [1 ]
Fujimoto, TT [1 ]
Tice, CM [1 ]
Michelotti, EL [1 ]
机构：
[1] Rohm & Haas Co, Spring House, PA 19477 USA
来源：
TETRAHEDRON | 2003年 / 59卷 / 13期
关键词：
phenylcyclohexenes; colchicine; epoxides;
D O I：
10.1016/S0040-4020(03)00216-3
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Colchicine mimetic (+/-)-4S,5R-4-nitro-5-(2,3,4-trimethoxyphenyl)cyclohexene (1) was epoxidized to afford a mixture of epoxides. The epoxides were separately converted in two steps, with high stereoselectivity, to two regioisomeric alpha-methoxyketones. One regioisomer, (+/-)-2R,4S,5R-2-methoxy-5-nitro-4-(2,3,4-trimethoxyphenyl)cyclohexanone (17), proved to be about 12-fold more potent than synthetic precursor 1 against HCT-116 tumor cells while the other regioisomer, (+/-)-2R,4R,5S-2-methoxy-4-nitro-5-(2,3,4-trimethoxyphenyl)cyclohexanone (16), and the synthetic intermediates tested showed no improvement in potency. (C) 2003 Published by Elsevier Science Ltd.
引用
收藏
页码：2223 / 2229
页数：7
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