Chemoenzymatic convergent synthesis of 2'-O,4'-C-methyleneribonucleosides

J Org Chem. 2014 Jul 3;79(13):6336-41. doi: 10.1021/jo5008338. Epub 2014 Jun 23.

Abstract

Novozyme-435-catalyzed efficient regioselective acetylation of one of the two diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d-ribofuranose has been achieved. The enzymatic methodology has been successfully utilized for convergent synthesis of bicyclic nucleosides (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme-435 can be used for 10 cycles of the acylation reaction without losing selectivity and efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Biocatalysis
  • Enzymes, Immobilized
  • Fungal Proteins
  • Lipase / chemistry*
  • Magnetic Resonance Spectroscopy
  • Monosaccharides / chemical synthesis*
  • Monosaccharides / chemistry
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Ribonucleosides / chemical synthesis*
  • Ribonucleosides / chemistry
  • Stereoisomerism

Substances

  • 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D-ribofuranose
  • Enzymes, Immobilized
  • Fungal Proteins
  • Monosaccharides
  • Nucleosides
  • Ribonucleosides
  • Novozyme 435
  • Lipase