Synthesis and mass spectral characterization of mycobacterial phosphatidylinositol and its dimannosides

J Org Chem. 2012 Aug 17;77(16):6743-59. doi: 10.1021/jo301189y. Epub 2012 Aug 7.

Abstract

A family of naturally occurring mycobacterial phosphatidylinositol (PI) and its dimannosides (PIM(2), AcPIM(2), and Ac(2)PIM(2)) that all possess the predominant natural 19:0/16:0 phosphatidyl acylation pattern were prepared to study their mass spectral fragmentations. Among these, the first synthesis of a fully lipidated PIM (i.e., (16:0,18:0)(19:0/16:0)-PIM(2)) was achieved from (±)-1,2:4,5-diisopropylidene-D-myo-inositol in 16 steps in 3% overall yield. A key feature of the strategy was extending the utility of the p-(3,4-dimethoxyphenyl)benzyl protecting group for its use at the O-3 position of inositol to allow installation of the stearoyl residue at a late stage in the synthesis. Mass spectral studies were performed on the synthetic PIMs and compared to those reported for natural PIMs identified from a lipid extract of M. bovis BCG. These analyses confirm that fragmentation patterns can be used to identify the structures of specific PIMs from the cell wall lipid extract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall / chemistry
  • Inositol / analogs & derivatives*
  • Magnetic Resonance Spectroscopy
  • Mannosides / chemical synthesis*
  • Molecular Weight
  • Mycobacterium bovis / chemistry*
  • Phosphatidylinositols / chemical synthesis*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Mannosides
  • Phosphatidylinositols
  • Inositol