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Synthesis of 6‐Substituted 2(1 H )‐Pyridon‐3‐yl C ‐2′‐Deoxyribonucleosides
Author(s) -
Chapuis Hubert,
Kubelka Tomáš,
Joubert Nicolas,
Pohl Radek,
Hocek Michal
Publication year - 2012
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.201101662
Subject(s) - deoxyribonucleosides , deoxyribonucleoside , chemistry , glycal , stereochemistry , nucleoside , protecting group , heck reaction , organic chemistry , palladium , stereoselectivity , catalysis , alkyl , enzyme
Two approaches to the synthesis of the title 6‐substituted 2(1 H )‐pyridon‐3‐yl C ‐2′‐deoxyribonucleosides have been pursued. A protected 6‐aminopyridine C ‐nucleoside intermediate was converted into the N ‐oxide followed by Ac 2 O‐mediated rearrangement and final deprotection to give 6‐acetylamino‐2‐oxo(1 H )‐pyridin‐3‐yl deoxyribonucleoside. Due to the unusually high stability of the N ‐acetyl group, the full deprotection was unsuccessful. In the second approach, 6‐chloro‐2‐pyridone was converted into phosphorodiamidate, which underwent ortho ‐magnesiation and iodination to give the 3‐iododerivative. It was then used in a Heck coupling with a sugar glycal and the resulting product deprotected to give 6‐chloro‐2‐oxo(1 H )‐pyridin‐3‐yl deoxyribonucleoside, which was either directly or after reprotection converted into 6‐methyl‐, 6‐amino‐, and 6‐unsubstituted pyridone C ‐nucleosides. The final nucleosides were very unstable and easily epimerized and/or oxidized, which limits (but not excludes) their further use in chemical biology.