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N(3) ‐Protection of Thymidine with Boc for an Easy Synthetic Access to Sugar‐Alkylated Nucleoside Analogs
Author(s) -
Simeone Luca,
De Napoli Lorenzo,
Montesarchio Daniela
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201100103
Subject(s) - alkylation , chemistry , thymidine , nucleoside , nucleobase , sugar , protecting group , nucleotide , combinatorial chemistry , nucleoside analogue , stereochemistry , dna , biochemistry , organic chemistry , catalysis , gene , alkyl
The use of Boc as a nucleobase‐protecting group in the synthesis of sugar‐modified thymidine analogs is reported. Boc was easily inserted at N(3) by a simple and high‐yielding reaction and found to be stable to standard treatments for the removal of Ac and t BuMe 2 Si (TBDMS) groups, as well as to ZnBr 2 ‐mediated 4,4′‐dimethoxytrityl (DMTr) deprotection. Boc Protection proved to be completely resistant to the strong basic conditions required to regioselectively achieve O ‐alkylation, therefore, providing synthetic access to a variety of sugar‐alkylated nucleoside analogs. To demonstrate the feasibility of this approach, two 3′‐ O ‐alkylated thymidine analogs have been synthesized in high overall yields and fully characterized.