AI Article Synopsis
- The sustainable chemical industry aims to develop efficient and safe methods for creating chiral building blocks from renewable resources.
- Research focuses on mandelate derivatives, important intermediates in pharmaceuticals, which currently rely on toxic cyanide for production.
- The study demonstrates a new biocatalytic approach using engineered (S)-4-hydroxymandelate synthase (HmaS) to synthesize both (S)- and (R)-mandelate derivatives with high efficiency and atom economy, offering a safer, cyanide-free production method.
Article Abstract
The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long-term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)-4-hydroxymandelate synthase (HmaS)-centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R-selective hydroxylation by single-point mutation, empowering the stereodivergent synthesis of both (S)- and (R)-mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide-free technology for greener and sustainable production of mandelate derivatives.
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| http://dx.doi.org/10.1002/anie.202300906 | DOI Listing |
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