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Nucleosides. 130 . Synthesis of 2′‐Deoxy‐2′‐substituted‐ and 5′‐Deoxy‐5′‐substituted‐ψ‐uridine Derivatives. Crystalline and Molecular Structure of 2′‐Chloro‐2′‐deoxy‐1,3‐dimethyl‐ψ‐uridine. Studies Directed Toward the Synthesis of 2′‐Deoxy‐2′‐substituted‐ arabino ‐Nucleosides. 1
Author(s) -
Pankiewicz Krzysztof W.,
Watanabe Kyoichi A.,
Takayanagi Hiroaki,
Itoh Tsueno,
Ogura Haruo
Publication year - 1985
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570220646
Subject(s) - chemistry , uridine , nucleophile , substituent , pyrimidine , nucleoside , derivative (finance) , stereochemistry , yield (engineering) , silylation , organic chemistry , catalysis , rna , biochemistry , materials science , metallurgy , financial economics , economics , gene
A method was developed to prepare 5′‐deoxy‐5′‐substituted‐ψ‐uridine derivatives 4 from 3′,5′‐ O ‐(1, 1, 3, 3‐tetraisopropyldisiloxanyl)‐1,3‐dimethyl‐ψ‐uridine 1 via a silyl rearrangement reaction. Nucleophilic displacement of the mesyloxy function of 2′‐ O ‐mesyl‐1,3‐dimethyl‐ψ‐uridine 7 afforded products with the 2′‐substituent in the “down” ribo configuration 8 . X‐Ray crystallographic analysis of the 2′‐chloro derivative 8a firmly established the molecular structure of 8 and provided evidence for neighboring group participation of the 4‐carbonyl function of 7 during the nucleophilic reactions. Treatment of 1,3‐dimethyl‐ψ‐uridine 11 with α‐acetoxyisobutyryl chloride afforded a mixture from which two 2′‐chloro‐2′‐deoxy‐ C ‐nucleosides were obtained. The major product (33% yield) was identical with 8 . The minor product (7% yield) was consequently assigned the arabino nucleoside 14 . This is the first direct introduction of a 2′‐substituent in the “up” configuration in a preformed pyrimidine nucleoside.