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A Convenient Route for the Synthesis of 3‐Deazaspongosine
Author(s) -
Bande Omprakash,
Herdewijn Piet
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301283
Subject(s) - chemistry , regioselectivity , nucleophile , raney nickel , stereoselectivity , nucleophilic substitution , pyridine , nucleobase , stereochemistry , alkoxide , combinatorial chemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry , dna
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 N 9 ‐β‐isomer. A final nucleophilic displacement of the 6‐chloride by hydrazine followed by reduction with Raney Nickel gave the desired 3‐deazaspongosine.