[(22R,23R)-3β-羟基-22,23-环氧-5α-麦角甾-8(14)-烯-15-酮：改进的合成方法及其对MCF-7细胞的毒性]

[(22R,23R)-3beta-Hydroxy-22,23-epoxy-5alpha-ergost-8(14)-en-15-one: improved synthesis and toxicity to MCF-7 cells].

作者信息

Mekhtiev A R, Timofeev V P, Misharin A Iu

机构信息

Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119992 Russia.

出版信息

Bioorg Khim. 2008 Nov-Dec;34(6):840-6.

PMID:19088760

Abstract

The chemical synthesis of (22R,23R)-3beta-hydroxy-22,23-epoxy-5alpha-ergost-8(14)-en-15-one from (22E)-3beta-acetoxy-5alpha-ergosta-7,14,22-triene was improved. The stages of obtaining and isomerizing (22E)-3beta-acetoxy-14alpha,15alpha-epoxy-5alpha-ergosta-7,22-diene were optimized. The introduction of the (22R,23R)-epoxide cycle was carried out by a basic treatment of intermediate (22S,23R)-3beta,23-diacetoxy-22-iodo-5alpha-ergost-8(14)-en-15-one. In cells of human mammary gland carcinoma MCF-7 (22R,23R)-3beta-hydroxy-22,23-epoxy-5alpha-ergost-8(14)-en-15-one showed a high toxicity (TC(50) = 0.4 +/- 0.1 microM for 48-h incubation in serum-free medium).

摘要

从（22E）-3β-乙酰氧基-5α-麦角甾-7,14,22-三烯化学合成（22R,23R）-3β-羟基-22,23-环氧-5α-麦角甾-8（14）-烯-15-酮的方法得到了改进。获得并异构化（22E）-3β-乙酰氧基-14α,15α-环氧-5α-麦角甾-7,22-二烯的步骤得到了优化。（22R,23R）-环氧环的引入是通过对中间体（22S,23R）-3β,23-二乙酰氧基-22-碘-5α-麦角甾-8（14）-烯-15-酮进行碱性处理来实现的。在人乳腺癌MCF-7细胞中，（22R,23R）-3β-羟基-22,23-环氧-5α-麦角甾-8（14）-烯-15-酮表现出高毒性（在无血清培养基中孵育48小时的半数毒性浓度（TC(50)）= 0.4 ± 0.1微摩尔）。