Synthesis of 1′-[14C]-stavudine® (d4T)

✍ Scribed by Robert P. Discordia

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 485 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199607)38:7<613::aid-jlcr873>3.0.co;2-x

✦ Synopsis

1-(1'-[14C1-2',3'-Dideoxy-~-~glyceropent-2'-enofuranosy~~thymine (1'-114C1-d4T), was synthesized kom l-[14Cl-ribose, 1, in 7 steps in an overall yield of 29.3%. 1-[14C]-Ribose was converted in one step to l-O-methy1-2,3,5-tri-O-benzoylribofuranoside 2 in quantitative yield. Compound 2 was converted to its p-1-0acetyltribenzoyl derivative, 5 which was coupled with thymine and subsequently deprotected to give l'-[14Cl-5-methyluridine, 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'-[14C]-5'-benzoyld4T, in 94.5% yield. Methanolysis of 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).