Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling

• 成果类型: Article
• 署名作者: Wang, Tian-Ci; Mai, Binh Khanh; Zhang, Zheng; Bo, Zhiyu; Li, Jiedong; Liu, Peng; Yang, Yang
• 署名单位: University of California System; University of California Santa Barbara; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Santa Barbara
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4407
• DOI: 10.1038/s41586-024-07284-5
• 发表日期: 2024-05-02
• 关键词: l-threonine aldolase; asymmetric-synthesis; gene cloning; enzymes; complexes

摘要

Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5 '-phosphate-dependent enzymes, threonine aldolases10-12, for the alpha-C-H functionalization of glycine and alpha-branched amino acid substrates by a radical mechanism, giving rise to a range of alpha-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology. We report on the oxidative cross-coupling of organoboron reagents and amino acids via pyridoxal biocatalysis to produce non-canonical amino acids, uncovering stereoselective, intermolecular free-radical transformations.