jo5019188_si_001.pdf (7.11 MB)
Resolution of Orthogonally Protected myo-Inositols with Novozym 435 Providing an Enantioconvergent Pathway to Ac2PIM1
journal contribution
posted on 2014-11-21, 00:00 authored by Alastair
M. M. Lee, Gavin F. Painter, Benjamin J. Compton, David S. LarsenOrthogonally
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.