Synthesis of Protected Amino Hexitol Nucleosides as Building Blocks for Oligonucleotide Synthesis

J Org Chem. 2018 Dec 21;83(24):15155-15169. doi: 10.1021/acs.joc.8b02444. Epub 2018 Dec 7.

Abstract

A new synthesis protocol for the preparation of hitherto unknown 1',5'-anhydro-4'-amino-trityl/MMTr hexitol nucleosides has been developed. Key steps in the synthesis of the pyrimidine analogues (U and C) include the regioselective d- allo-hexitol oxirane and 2',4'-anhydronucleoside ring opening by uracil and azide, respectively. A different strategy using a regioselective epoxide ring opening of d- gulo-oxirane, followed by a SN2 type of azidation reaction, has been adopted for the purine analogues (A and G). These compounds can be easily converted to 6'-phosphoramidites for the solid-phase synthesis of N4' → P6' phosphoramidates of amino hexitol nucleic acids (AHNA).

MeSH terms

  • Chemistry Techniques, Synthetic
  • Epoxy Compounds / chemistry
  • Oligonucleotides / chemical synthesis*
  • Oligonucleotides / chemistry*
  • Stereoisomerism
  • Sugar Alcohols / chemistry*

Substances

  • Epoxy Compounds
  • Oligonucleotides
  • Sugar Alcohols
  • hexitol