Synthesis of [5-14C]pentostatin, an antileukemic agent and potent adenosine deaminase inhibitor

✍ Scribed by Peter W. K. Woo; Helen T. Lee

• Book ID: 102372830
• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: French
• Weight: 426 KB
• Volume: 28
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580280412

✦ Synopsis

Abstract

Reaction of triethyl ortho[^14^C]formate (2) with 2‐amino‐1‐(5‐amino‐1H‐imidazol‐4‐yl)ethanone dihydrochloride (1) in the presence of molecular sieves 4A gave 6,7‐dihydro[5‐^14^C]imidazo[4,5‐d][1,3]diazepin‐8(3H)‐one hydrochloride monodimethyl sulfoxide (3) (radiochemical yield, 60%). The latter was persilylated with bis(trimethylsilyl)trifluroacetamide (4) and glycosylated with 2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranosyl chloride (6) to give a mixture from which the 3‐N‐β‐glycosylated product 8 was isolated by chromatography and crystallization (13%). Deprotective saponification with methanolic sodium methoxide and subsequent sodium borohydride reduction of the 8‐keto function gave a (R,S)‐mixture from which the desired (R)‐isomer, [5‐^14^C]pentostatin (11), was isolated by preparative HPLC over a C18 column, desalting with Diaion‐HP20, and subsequent crystallization (39%).