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Synthesis of 1′‐[ 14 C]‐stavudine® (d4T)
Author(s) -
Discordia Robert P.
Publication year - 1996
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199607)38:7<613::aid-jlcr873>3.0.co;2-x
Subject(s) - stavudine , chemistry , stereochemistry , virology , human immunodeficiency virus (hiv) , zidovudine , viral disease , biology
1‐(1′‐[ 14 C]‐2′,3′‐Dideoxy‐β‐D‐glyceropent‐2′‐enofuranosyl)thymine (1′‐[ 14 C]‐d4T), was synthesized from 1‐[ 14 C]‐ribose, 1, in 7 steps in an overall yield of 29.3%. 1‐[ 14 C]‐Ribose was converted in one step to 1‐ O ‐methyl‐2,3,5‐tri‐ O ‐benzoylribo‐furanoside 2 in quantitative yield. Compound 2 was converted to its β‐1‐ O ‐acetyltribenzoyl derivative, 3, which was coupled with thymine and subsequently deprotected to give 1′‐[ 14 C]‐5‐methyluridine, 5, in 56.0% yield from 1. Compound 5 was converted to its 2′,3′,5′‐tri‐ O ‐methanesulfonate derivative, 6, in quantitative yield. In a "one‐pot" transformation involving three consecutive transformations, compound 6 was converted to 1′‐[ 14 C]‐5′‐benzoyl‐d4T, 10, in 94.5% yield. Methanolysis of 10 followed by flash chromatography gave the title compound in 79.0% yield (99.9% radiochemical purity, and 98.6% potency as determined by HPLC weight assay).