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Synthesis of [5‐ 14 C]pentostatin, an antileukemic agent and potent adenosine deaminase inhibitor
Author(s) -
Woo Peter W. K.,
Lee Helen T.
Publication year - 1990
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/jlcr.2580280412
Subject(s) - chemistry , sodium methoxide , sodium borohydride , diastereomer , trimethylsilyl , saponification , deoxygenation , column chromatography , epimer , isopropylamine , medicinal chemistry , hydrochloride , yield (engineering) , sulfoxide , organic chemistry , nuclear chemistry , methanol , catalysis , materials science , metallurgy
Reaction of triethyl ortho[ 14 C]formate ( 2 ) with 2‐amino‐1‐(5‐amino‐1 H ‐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(3 H )‐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%).