Study on the Conversion of Natural Sterols into Useful Steroids

天然甾醇转化为有用类固醇的研究

• 批准号: 59870068
• 负责人: IKEKAWA Nobuo
• 金额: $ 3.9万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research
• 财政年份: 1984
• 资助国家: 日本
• 起止时间: 1984 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59870068/
• 关键词: Microbial sterol side chain cleavage; Inhibitor; microbial trasformation; Cholesterol; シトステロール; ステロール代謝

In this project we have attempted to accumulate useful stroids such as C-24-carboxylic acid in the fermentation of cholesterol or sitosterol with a microorganism which is capable of degrading sterol side chain. For this purpose we have prepared several steroidal compounds as analogs of the C-24 acid, hoping their inhibitory action at a certain stage of multi-step enzymatic reactions in the sterol side chain degradation.The compounds synthesized are as follows: methyl 3 <beta> -hydroxy-chol-5-en-22-yn-24-oate (1), methyl 3 <beta> -hydroxychol-5-en-23-yne-24-carboxylate (2), methyl 23-bromo-3 <beta> -hydroxychol-5-en-24-oate (3), methyl 23,23-difluoro-3 <beta> -hydroxychol-5-ene-24-oate (4), methyl 24,24-difluoro-3 <beta> -hydroxychol-5-ene-24-carboxylate (5).When cholesterol was incubated with Mycobacterium sp. NRRL 3805 in the presence of these compounds, the formation of androst-4-ene-3,17-dione was decreased. Among them, compound (4) exhibited the strongest inhibitory action against the cholesterol degradation. In contrast, these compounds did not inhibit the cholesterol dagradation in the form of free acid instead of methyl ester. However, accumulation of intermediate sterols were not observed, which suggests that a feed-back inhibition which blocks 26-hydroxylation is operative.

在本项目中，我们试图在胆固醇或谷甾醇的发酵中用能够降解甾醇侧链的微生物积累有用的甾醇类化合物，如C-24-羧酸。本文合成了几种甾体化合物作为C-24酸的类似物，希望它们在甾醇侧链降解的多步酶促反应的某一阶段具有抑制作用，所合成的化合物如下：3<beta>-羟基-胆-5-烯-22-炔-24-酸甲酯（1）、3<beta>-羟基-胆-5-烯-23-炔-24-羧酸甲酯（2）、23-溴-3<beta>-羟基-胆-5-烯-24-酸甲酯（3）、23，23-二氟-3<beta>-羟基-胆-5-烯-24-酸甲酯（4）、24，24-二氟-3<beta>-羟基-胆-5-烯-24-羧酸甲酯（5）。雄甾-4-烯-3，17-二酮的形成减少。其中化合物（4）对胆固醇降解的抑制作用最强。与此相反，这些化合物不抑制胆固醇降解的形式，游离酸，而不是甲酯。然而，没有观察到中间甾醇的积累，这表明阻断26-羟基化的反馈抑制是有效的。

项目成果

Chem.Pharm.Bull.34. (1986)

Chem.Pharm.Bull.34。

M. Ohtsuka, Y. Fujimoto, N. Ikekawa: "Steroidal Inhibitors of Microbial Degradation of Sterol Side Chain" Chem Pharm. Bull.34. 2780-2785 (1986)

M. Ohtsuka、Y. Fujimoto、N. Ikekawa：“甾醇侧链微生物降解的甾体抑制剂” Chem Pharm。