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Synthesis of carbon‐14 labeled CI‐1012 and CI‐1013, potential anti‐HIV agents
Author(s) -
Woo Peter W. K.,
Pu YuMing,
Huang Che C.
Publication year - 1999
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(199909)42:9<827::aid-jlcr243>3.0.co;2-v
Subject(s) - chemistry , thionyl chloride , benzoic acid , benzamide , trifluoroacetic acid , aniline , medicinal chemistry , pyridine , bromide , benzoyl chloride , organic chemistry , chloride , stereochemistry
14 C‐Labeled CI‐1012 and CI‐1013 of the 2,2′‐dithiobis[benzamide] and benzisothiazolone series, inhibitors of viral replication and potential anti‐HIV agents, were prepared. The radiolabeling of CI‐1013, a six‐step synthetic sequence, started with the treatment of N ‐ t ‐BOC‐aniline ( 2 ) with 2·0 equivalents of t ‐BuLi, followed by carboxylation of the ortho ‐lithiated center in the resulting lithiated dianion 2b with [ 14 C]carbon dioxide, to give N ‐ t ‐BOC‐2‐Amino‐[7‐ 14 C]benzoic acid ( 3 ). Product 3 was then deprotected with trifluoroacetic acid to give 2‐Amino‐[7‐ 14 C]benzoic acid as its TFA salt ( 4 ). The latter was diazotized and treated with Na 2 S 2 , generated in situ, to give 2,2′‐dithiobis[7‐ 14 C]benzoic acid ( 5 ). The acid chloride from 5 , obtained by treatment with thionyl chloride, was subsequently coupled with L‐isoleucine tert ‐butyl ester and deprotected with TFA to produce [ S ‐( R *, R *)]‐2‐{2‐[2‐(1‐Carboxy‐2‐methylbuty)[ 14 C]carb‐amoyl)phenyldisulfanyl]‐[7‐ 14 C]benzoylamino}‐3‐methylpentanoic acid ([ 14 C 2 ]CI‐1013) ( 8 ). Treatment of 8 with bromine yielded the benzisothiazolene, [ S ( R *, R *)]‐3‐Methyl‐2‐(3‐oxo‐3 H ‐[3‐ 14 C]benz[ d ]isothiazol‐2‐yl)pentanoic acid ([ 14 C]CI‐1012) ( 9 ). Copyright © 1999 John Wiley & Sons, Ltd.