Chemoenzymatic protocols synthesis

SCHEME 6.18. Chemoenzymatic protocol for the continuous flow synthesis of epoxides. 

Yu H, Chokhawala HA, Huang S, Chen X. One-pot three-enzyme chemoenzymatic approach to the synthesis of sialosides containing natural and non-natural functionalities. Nature Protocols 2006 1 2485-2492. 

So far, the most efficient protocols for the chemoenzymatic large-scale (multigram) syntheses of GDP-Fuc and analogs, starting from commercially available fucose, have recently been published by Baisch and Ohrlein [163], In this seven-step synthesis, the crucial last step is the enzymatic deprotection of the triacetylated fucose moiety with acetylesterase from orange peel (Fig. 9). 

The substrate scope of the DKR protocol above was extended to include a wide range of primary amines [89]. Functional groups tolerated include fluorine, bromine, nitrile, nitrate, and trifluoromethyl. Aliphatic amines and more sterically hindered substrates were also obtained in high yields and ee values. The method was found applicable with both isopropenyl acetate and dibenzyl carbonate as acyl donors. For 18 different substrates, the corresponding enantiomericafly pure products were obtained in high to excellent yields (70-95%) and with high to excellent ee values (93 to >99%). The chemoenzymatic DKR protocol was also applied to the synthesis of norsertraline, from readily available 1,2,3,4-tetrahydro-l-naphthyl-amine. Norsertraline is cmrently in clinical trials for the treatment of central nervous system (CNS) disorders. 

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