摘要
雄甾-4-烯-3,17-二酮(4AD)是甾体化合物合成过程中的关键中间体,其羟化产物通常具有良好的药理活性或作为工业生产甾体药物的重要中间体。利用粉红单端孢Trichothecium roseum对4AD进行生物转化,从其发酵提取物中共分离鉴定了3个4AD羟基化产物:6β-羟基-雄甾-4-烯-3,17-二酮(6β-OH-4AD,1),14α-羟基-雄甾-4-烯-3,17-二酮(14α-OH-4AD,2),6β,14α-双羟基-雄甾-4-烯-3,17-二酮(6β,14α-di-OH-4AD,3),表明T.roseum对4AD的C-6β位和C-14α位具有较强的羟化能力,其中14α-OH-4AD(2)可作为合成强心甾类化合物毛地黄毒素的重要中间体,6β,14α-di-OH-4AD(3)可作为合成具有抗肿瘤活性的14α-羟基-雄甾-4-烯-3,6,17-三酮的重要中间体。提供了1株能够高效制备活性甾醇中间体14α-OH-4AD和6β,14α-di-OH-4AD的菌株,同时可为研究其他甾醇药物奠定基础。
Androst-4-en-3,17-dione(4AD)is key intermediate in the synthesis of steroids,whose hydroxylation products usually have pharmacological activities or play important roles in industrial production of steroid drugs.In the present study,we isolated and identified three hydroxylated products of 4AD including 6β-hydroxyandrost-4-en-3,17-dione(6β-OH-4AD,1),14α-hydroxyandrost-4-en-3,17-dione(14α-OH-4AD,2),and 6β,14α-Dihydroxyandrost-4-en-3,17-dione(6β,14α-diOH-4AD,3)from the extract of the fermentation broth of Trichothecium roseum feeding 4AD,demonstrating the highly efficient transformation capability of T.roseum on C-6βand C-14αof 4AD.Among three hydroxylated products,14α-OH-4AD(2)could be used as the key intermediate in the synthesis of cardiotonic steroid digitoxin;6β,14α-di-OH-4AD(3)could be the key intermediate in the synthesis of 14α-hydroxyandrost-4-en-3,6,17-one that has antitumor activity.This study provided the strain which could efficiently prepare the active sterol intermediates 14α-OH-4AD and 6β,14α-di-OH-4AD,providing the foundation for future research on other sterol drugs.
作者
彭雨
王越
张莹璐
陈天娇
陈晶晶
杨金玲
巩婷
朱平
PENG Yu;WANG Yue;ZHANG Yinglu;CHEN Tianjiao;CHEN Jingjing;YANG Jinling;GONG Ting;ZHU Ping(State Key Laboratory of Bioactive Substance and Function of Natural Medicines&Key Laboratory of Biosynthesis of Natural Products of the National Health Commission,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)
出处
《菌物研究》
CAS
CSCD
2023年第1期178-183,共6页
Journal of Fungal Research
基金
国家重点研发计划项目(2020YFA0908003)
中国医学科学院医学与健康科技创新工程重大协同创新项目(CIFMS2021-I2M-1-029)
