Stereoselective and Divergent Aza-Adenosine and Aza-Guanosine Syntheses from Xylofuranose, the Key Fragments of a STING Cyclic Dinucleotide Agonist

J Org Chem. 2022 Feb 18;87(4):1925-1933. doi: 10.1021/acs.joc.1c00984. Epub 2021 Jul 14.

Abstract

The stereoselective and divergent synthesis of two aza-nucleosides is reported. Starting from xylofuranose 9, aza-adenosine 2 was prepared in 13 steps and 7% overall yield, and aza-guanosine 3 was prepared in 13 steps and 7.8% overall yield. Compared to the original syntheses, some advantages of these new routes are significant yield improvement, overall step-count reduction, an optimized protecting group strategy, the development of a versatile platform for nitrogenous base incorporation, and the elimination of hazardous reagents (e.g., benzyl isocyanate, Et3N·HF).

MeSH terms

  • Adenosine*
  • Guanosine
  • Nucleosides*

Substances

  • Nucleosides
  • Guanosine
  • Adenosine