{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ren X"],"funding":["National Institutes of Health","NIH HHS","NIGMS NIH HHS","National Science Foundation"],"pagination":["8550-8556"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9337741"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(29)"],"pubmed_abstract":["Organophosphonate compounds have represented a rich source of biologically active compounds, including enzyme inhibitors, antibiotics, and antimalarial agents. Here, we report the development of a highly stereoselective strategy for olefin cyclopropanation in the presence of a phosphonyl diazo reagent as carbene precursor. In combination with a 'substrate walking' protein engineering strategy, two sets of efficient and enantiodivergent myoglobin-based biocatalysts were developed for the synthesis of both (1<i>R</i>,2<i>S</i>) and (1<i>S</i>,2<i>R</i>) enantiomeric forms of the desired cyclopropylphosphonate ester products. This methodology enables the efficient transformation of a broad range of vinylarene substrates at a preparative scale (<i>i.e.</i> gram scale) with up to 99% de and ee. Mechanistic studies provide insights into factors that contribute to make this reaction inherently more challenging than hemoprotein-catalyzed olefin cyclopropanation with ethyl diazoacetate investigated previously. This work expands the range of synthetically useful, enzyme-catalyzed transformations and paves the way to the development of metalloprotein catalysts for abiological carbene transfer reactions involving non-canonical carbene donor reagents."],"journal":["Chemical science"],"pubmed_title":["Highly stereoselective and enantiodivergent synthesis of cyclopropylphosphonates with engineered carbene transferases."],"pmcid":["PMC9337741"],"funding_grant_id":["CHE-0946653","S10OD030302","S10 OD025242","GM098628","CHE-1725028","R01 GM098628","S10 OD030302","CBET-1929256","CBET 1929237"],"pubmed_authors":["Ren X","Khare SD","Shen Z","Chandgude AL","Fasan R","Carminati DM"],"additional_accession":[]},"is_claimable":false,"name":"Highly stereoselective and enantiodivergent synthesis of cyclopropylphosphonates with engineered carbene transferases.","description":"Organophosphonate compounds have represented a rich source of biologically active compounds, including enzyme inhibitors, antibiotics, and antimalarial agents. Here, we report the development of a highly stereoselective strategy for olefin cyclopropanation in the presence of a phosphonyl diazo reagent as carbene precursor. In combination with a 'substrate walking' protein engineering strategy, two sets of efficient and enantiodivergent myoglobin-based biocatalysts were developed for the synthesis of both (1<i>R</i>,2<i>S</i>) and (1<i>S</i>,2<i>R</i>) enantiomeric forms of the desired cyclopropylphosphonate ester products. This methodology enables the efficient transformation of a broad range of vinylarene substrates at a preparative scale (<i>i.e.</i> gram scale) with up to 99% de and ee. Mechanistic studies provide insights into factors that contribute to make this reaction inherently more challenging than hemoprotein-catalyzed olefin cyclopropanation with ethyl diazoacetate investigated previously. This work expands the range of synthetically useful, enzyme-catalyzed transformations and paves the way to the development of metalloprotein catalysts for abiological carbene transfer reactions involving non-canonical carbene donor reagents.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-06-01T01:57:39.355Z","creation":"2024-11-14T15:34:13.672Z"},"accession":"S-EPMC9337741","cross_references":{"pubmed":["35974764"],"doi":["10.1039/d2sc01965e"]}}