The Enantioselective Synthesis of Some Useful Antibiotics based on the Chemicoenzymatic Strategy.

基于化学酶策略的一些有用抗生素的对映选择性合成。

• 批准号: 59430024
• 负责人: OHNO Masaji
• 金额: $ 17.22万
• 依托单位: Faculty of Pharmaceutical Sciences, University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 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/grant/KAKENHI-PROJECT-59430024/
• 关键词: Pig liver esterase; Synthesis of antibiotics; Symmetrization-asymmetrization concept; Retrosynthesis; Fortimicine; リゾチシン; 豚肝臓エステラーゼ; 4-シクロヘキセン-1; 2-シス-ジカルボン酸メチルエステル; カルバペネム; ミルベマイシン; アバメクチン; リゾキシン

Since 1978, we have begun to synthesize biologically active natural products by a reasonable combination of enzymatic process (pig liver esterase, PLE) and usual organic synthesis and developed a new avenue for natural product synthesis. Our synthetic strategy for obtaining various antibiotics has therefore been designed as follows.(1) Retrosynthesis is performed to generate, from the target molecule, a symmetric diester in the prochiral or meso form.(2) The symmetric diester is subjected to asymmetric hydrolysis with pig liver esterase to generate the corresponding chiral half-ester. (enzymatic conversion of <sigma> -symmetry to <C_1> -symmetry)(3) The chiral half-ester is converted to the target molecule by means of organic synthesis. The total strategy is called "Symmetrization-asymmetrization Concept".Thus, in addition to various carbapenem antibiotics and nucleosides, fortimicin A and part of rhizoxin were synthesized and the results were presented at various famous international meetings of the world.

自1978年以来，我们开始将酶法（猪肝酯酶，PLE）与常用的有机合成方法合理结合，合成具有生物活性的天然产物，开辟了天然产物合成的新途径。因此，我们获得各种抗生素的合成策略设计如下。(1)从目标分子中进行反合成以产生前手性或介观形式的对称二酯。(2)对称双酯与猪肝酯酶进行不对称水解，生成相应的手性半酯。（酶促将<sigma> -对称转化为<C_1> -对称）(3)通过有机合成将手性半酯转化为靶分子。总策略称为“对称-不对称概念”。因此，除了各种碳青霉烯类抗生素和核苷外，还合成了福替米星A和部分根毒素，并在世界各著名国际会议上发表了成果。

项目成果

Tetrahedron Letters. 26. (1985)

四面体字母。

IUPAC第5回国際有機合成化学会議. (1985)

IUPAC 第五届国际合成有机化学会议（1985 年）。

大野雅二,大村智編著: "抗生物質研究の最先端" 東京化学同人, (1987)

Masaji Ohno、Satoshi Omura（编辑）：“抗生素研究的前沿”东京化学同人，（1987）

Masaji Ohno, Satoru Ohmura: Tokyo Kagaku Dohjin. Recent Advances on Antibiotic Research, (1987)

大野雅司、大村悟：东京化学同人。

大野雅二編著: "酵素機能と精密有機合成" シーエムシー, (1984)

大野正治主编：《酶的功能与精密有机合成》CMC，（1984）