酵素类固态合成阿扎斯皮罗
Jennifer L Kennemur1, Yueming Long1, Catherine J Ko1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
我们开发了一种新型的生物催化方法, 这种立体分离平台使用工程酶进行高效和选择性生产,
科学领域:
- 生物催化和有机合成
- 药物化学和药物发现
背景情况:
- 酸是药物研究中的重要支架.
- 现有的方法缺乏对称的催化方法来合成它们.
研究的目的:
- 开发一种合成阿扎斯皮罗的立体分离生物催化平台.
- 在合成这些有价值的化合物中获得高产量和选择性.
主要方法:
- 使用基于原蛋白的工程酶作为碳转移酶催化剂.
- 进行了不和外环N-异环的循环化.
- 使用冷解大肠杆菌溶解剂作为无有机辅溶剂的催化剂.
主要成果:
- 获得高产量 (21-99%) 和优秀的立体选择性 (dr和er值高达99.5:0.5).
- 在高基底度 (高达150mM) 的克尺度上证明了可扩展性.
- 成功合成了结构多样化和药物相关的阿扎斯皮罗.
结论:
- 提出了一个实用,可扩展和立体分离的阿扎斯皮罗[2.y]的生物催化合成.
- 强调了低成本的工程原蛋白及其原生铁辅因子的使用.
- 建立了一种更环保,更有效的方法来获取关键的药物中间产品.
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相关概念视频
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
