Chemoenzymatic synthesis of d-biotin intermediate lactone via lipase-catalyzed desymmetrization of meso diols

A chemoenzymatic methodology for the asymmetric synthesis of d -biotin intermediate lactone ((3a S , 6a R )-tetrahydro-1,3-dibenzylhexahydro-1 H -Furo[3,4-d] imidazole-2,4-dione) 1 has been demonstrated. The key step of the synthetic routes is Lipozyme RM IM catalyzed desymmetrization of meso-diols 3 . The highest enantiomeric excess ( e.e.   >   98%) and yield (>90%) of the product was achieved with Lipozyme RM IM in Dioxane/Toluene (1:3, v/v) at 35   °C. Furthermore, Lipozyme RM IM showed an excellent operational stability, retaining above 80% of the initial activity after 10 cycles of reaction. d -Biotin intermediate lactone 1 was obtained subsequently by Jones oxidation, basic hydrolysis and lactonization.