【Frontiers in HaiChuan Chemical Technology】Progress achieved in the research of α-hydroxymethyl analogs

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Recently, a research team from the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, achieved the efficient synthesis of structurally diverse α-hydroxymethyl analogs, and developed a one-pot multi-enzyme reaction system that enabled the efficient synthesis of 1,2-diol compounds with complementary enantioselectivity. This study provides an efficient and green approach for synthesizing important multifunctional, high-value compounds starting from simple compounds such as formaldehyde and other aldehydes. 　　α-Hydroxymethyl and chiral 1,2-diol compounds are important structural units in various natural products and drug molecules. Using the biocatalyst ThDP-dependent enzyme, α-hydroxymethyl compounds can be synthesized from formaldehyde and other simple aldehydes through intermolecular C-C bond-forming reactions, but practical application faces challenges. 　　Through protein engineering of benzaldehyde lyase, the research team obtained mutant enzymes with improved catalytic activity, chemical selectivity, and tolerance to aldehyde substrates, enabling the efficient synthesis of structurally diverse α-hydroxymethyl analogs with few self-imine byproducts, and achieving a separation yield of 68% to 89%. Based on this, the team developed a one-pot multi-enzyme reaction system, overcoming the challenge of enzyme combination and enabling the efficient synthesis of enantioselectively complementary 1,2-diol compounds.