Resolution of orthogonally protected myo-inositols with novozym 435 providing an enantioconvergent pathway to Ac2PIM1.

Abstract

Orthogonally protected chiral myo-inositol derivatives are important intermediates for higher order myo-inositol-containing compounds. Here, the use of the immobilized enzyme Novozym 435 to efficiently catalyze the acetylation of the 5R configured enantiomer of racemic 1,2-O-isopropylidene-myo-inositols possessing chemically and sterically diverse protecting groups at O-3 and O-6 is described. The resolutions were successful with allyl, benzyl, 4-bromo-, 4-methoxy-, 4-nitro-, and 4-(3,4-dimethoxyphenyl)benzyl, propyl, and propargyl protection at O-6 in combination with either allyl or benzyl groups at O-3. Bulky protecting groups slow the rate of acetylation. No reaction was observed for 3,6-di-O-triisopropylsilyl-1,2-O-isopropylidene-myo-inositol. The utility of this methodology was demonstrated by the first reported synthesis of an Ac2PIM1 (9), which used both enantiomers of the resolved 3-O-allyl-6-O-benzyl-1,2-O-isopropylidene-myo-inositol in a convergent synthesis.