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

•A methodology for chemoenzymatic synthesis of d-biotin intermediate lactone.•Lipozyme RM IM catalyzed enantioselective transesterification of meso-diols.•The d-biotin intermediate lactone was obtained in high e.e. (>98%) and yield (65%).

A chemoenzymatic methodology for the asymmetric synthesis of d-biotin intermediate lactone ((3aS, 6aR)-tetrahydro-1,3-dibenzylhexahydro-1H-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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide