Nucleosides. <b>130</b>. 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‐<i>arabino</i>‐Nucleosides. <b>1</b>

Abstract

Abstract 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.