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

J Org Chem. 2014 Nov 21;79(22):10916-31. doi: 10.1021/jo5019188. Epub 2014 Nov 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzymes, Immobilized
  • Fungal Proteins
  • Inositol / chemistry*
  • Inositol 1,4,5-Trisphosphate / chemical synthesis*
  • Inositol 1,4,5-Trisphosphate / chemistry
  • Lipase / chemistry*
  • Molecular Structure
  • Stereoisomerism

Substances

  • Enzymes, Immobilized
  • Fungal Proteins
  • Inositol
  • Inositol 1,4,5-Trisphosphate
  • Novozyme 435
  • Lipase