Stereoselective Chemoenzymatic Cascades for the Synthesis of Densely Functionalized Iminosugars
Christopher R B Swanson1, Léa Gourbeyre1, Grayson J Ford1
1Manchester Institute of Biotechnology, School of Chemistry, The University of Manchester, 131 Princess Street, M1 7DN Manchester, United Kingdom.
Abstract:
1,4-Dicarbonyls are versatile synthons for the construction of diverse pharmacophores and natural products. However, the stereoselective synthesis of densely functionalized 1,4-dicarbonyls is challenging. Here, we report a versatile biocatalytic route to access chiral 2,3-dihydroxy-1,4-diketones in high yields and up to gram scale using d-fructose-6-phosphate aldolase (EcFSA). The utility of these compounds as synthons is exemplified in enzyme cascades with subsequent regio- and stereoselective enzymatic transamination to form densely functionalized homochiral 1-pyrrolines followed by chemical or enzymatic reduction to tetrasubstituted pyrrolidines.
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