Abstract

Microbial mediated, especially the fungi mediated asymmetric reduction of the ketone is one of the most promising tools for the synthesis of chiral alcohols. Many fungal cultures were isolated from soil and screened for the stereo selective bioreduction of acetophenone. The potential isolates are characterised using molecular techniques and found to be Penicillium rubens VIT SS1 (Genbank ID: MK063869) and Penicillium citrinum VIT SS2 (Genbank ID: MW960208). Both the isolates were tested for the bioreduction of few aromatic ketones such as 4-fluoro acetophenone, 3-hydroxy acetophenone, and oxcarbazepine, which are the key chiral intermediates of various pharmaceutical drugs. The P. rubens VIT SS1 produced (S)-alcohol obeying Prelog’s rule, and P. citrinum was anti-Prelog configuration in nature. Preparatory scale reactions were conducted using the optimised bioreduction process, and the keto loading was significantly increased by 12-fold (from 0.5 to 6 g/L) with >99% conversion and >98% enantiomeric excess. The study discloses the vast prospective approach of exploring filamentous fungi for sustainable synthesis of chiral alcohols in an environment-friendly, novel, and cost competent way.

摘要

微生物介导，尤其是真菌介导的酮不对称还原是合成手性醇最有前途的工具之一。从土壤中分离出许多真菌培养物并筛选苯乙酮的立体选择性生物还原。使用分子技术对潜在的分离株进行了表征，发现它们是青霉菌VIT SS1（基因库 ID：MK063869）和柑橘青霉VIT SS2（基因库 ID：MW960208）。对这两种分离物都进行了一些芳香酮的生物还原测试，例如 4-氟苯乙酮、3-羟基苯乙酮和奥卡西平，它们是各种药物的关键手性中间体。产生的P. rubens VIT SS1 ( S)-酒精遵循 Prelog 的规则，而P. citrinum本质上是反 Prelog 配置。使用优化的生物还原工艺进行制备规模反应，酮负载显着增加了 12 倍（从 0.5 到 6 g/L），转化率 >99% 和对映体过量 >98%。该研究揭示了探索丝状真菌以环境友好、新颖且具有成本效益的方式可持续合成手性醇的广阔前景。