Resolution of Orthogonally Protected <i>myo</i>-Inositols with Novozym 435 Providing an Enantioconvergent Pathway to Ac<sub>2</sub>PIM<sub>1</sub>
2014-11-21T00:00:00Z (GMT) by
Orthogonally protected chiral <i>myo-</i>inositol derivatives are important intermediates for higher order <i>myo</i>-inositol-containing compounds. Here, the use of the immobilized enzyme Novozym 435 to efficiently catalyze the acetylation of the 5<i>R</i> configured enantiomer of racemic 1,2-<i>O</i>-isopropylidene-<i>myo</i>-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-<i>O</i>-triisopropylsilyl-1,2-<i>O</i>-isopropylidene-<i>myo</i>-inositol. The utility of this methodology was demonstrated by the first reported synthesis of an Ac<sub>2</sub>PIM<sub>1</sub> (<b>9</b>), which used both enantiomers of the resolved 3-<i>O</i>-allyl-6-<i>O</i>-benzyl-1,2-<i>O</i>-isopropylidene-<i>myo</i>-inositol in a convergent synthesis.