StereoselectiveChemoenzymatic Cascades for the Synthesisof Densely Functionalized Iminosugars

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 (<i>Ec</i>FSA). 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.