V. Mitteilung über Nucleoside. Über den Desoxyribonucleinsäure-Baustein 5-Hydroxymetyl-2’-desoxy-uridin sowie sein α-Anomeres

Abstract

Benzylation of 5-hydroxymethyl-uracil to 5-benzyloxy-methyl-uracil readily takes place. This compound is well suited for use in the preparation of nucleosides with labile sugars. The Hg salt IX can be obtained according to an improved procedure. It condenses with 3,5-di-p-methyl-benzoyl-2-deoxy-D-ribofuranosylchloride under mild conditions (room temperature) to give crystalline, completely substituted, anomeric nucleosides in high yields. The more interesting B-nucleoside is quantitatively formed (based on optimal yields in regard to the "trans"-rule), the a-nucleoside in 35% yield. The chemical structure was proved by 3 independent means: conversion to thymidine, NMR [nuclear magnetic resonance]-spectroscopy and measurement of optical rotatory dispersion (Cotton-effect). Catalytic hydrogenation and deacylation produces free deoxyribosides. In this simple manner naturally occuring crystalline 5-hydroxymethyl-2[image]-deoxyuridine may be obtained on a preparative scale (approx. 45% yields based on IX). The respective crystalline a-anomer (23-32%) as well as the whole a series were not previously known. Conversion of a and B benzylether nucleosides readily leads to valuable synthetic intermediates e.g. for the preparation of nucleotides. 5-Chloromethyl uracil nucleoside XX reacts with nucleophilic compounds, e.g. alcohols, amines. They are thus bound to the thymidine residue which acts as a mobile carrier.