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

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.

Synthesis of Helix 69 of Escherichia coli 23S rRNA Containing Its Natural Modified Nucleosides, m3Ψ and Ψ

“…The 1-acetylpseudouridine product was methylated to give 3-methylpseudouridine; however, the assignment of the regiochemistry of the methyl group at N3 was ambiguous. The reported chemical shift of the methyl group in DMSO was shifted by ∼0.8 ppm (2.52 ppm) compared to those in other spectra of methylated pseudouridine taken in the same solvent (3.29 ppm). , The synthesis reported by Kowalak et al was motivated by the desire to identify 3-methylpseudouridine in E. coli 23S rRNA by mass spectrometry . For that reason, their synthesis was only carried out on the milligram scale, and the product was not characterized by NMR.…”