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Keywords:

  • Ribonucleosides;
  • Nitrogen heterocycles;
  • Glycosylation;
  • Nucleobases;
  • Nucleosides;
  • Aromatic substitution

Abstract

The first chemical synthesis of the 3-deazaspongosine nucleoside is described, starting from commercially available 4-amino-2,6-dichloropyridine. The key step is the introduction of required functional groups at the 2 and 6 positions of the 4-amino-3-nitropyridine without any conflict in the synthesis of nucleobase. Regioselective nucleophilic substitution with allyl alkoxide at the 2 position of 4-amino-2,6-dimethoxypyridine, followed by sequential deallylation and chlorination led to the desired 2-chloro derivative. Ring closure of the 3,4-diaminopyridine and stereoselective glycosylation of the imidazo[4,5-c]pyridine with tetraacetate-protected ribofuranose gave only the N9-β-isomer. A final nucleophilic displacement of the 6-chloride by hydrazine followed by reduction with Raney Nickel gave the desired 3-deazaspongosine.