Synthesis of carbon-14 labeled CI-1012 and CI-1013, potential anti-HIV agents.

C-14 -Labeled CI-1012 and CI-1013 of the 2,2'-dithiobis[benzamide] and benz isothiazolone series, inhibitors of viral replication and potential anti-HI V agents, were prepared. The radiolabeling of CI-1013, a six-step synthetic sequence, started with the treatment of N-t-BOC-aniline ((2) under bar) wi th 2.0 equivalents of t-BuLi, followed by carboxylation of the ortho-lithia ted center in the resulting lithiated dianion <(2b)under bar> with [C-14]ca rbon dioxide, to give N-t-BOC-2-Amino-[7-C-14]benzoic acid ((3) under bar). Product (3) under bar was then deprotected with trifluoroacetic acid to gi ve 2-Amino-[7-C-14]benzoic acid as its TFA salt ((4) under bar) The latter was diazotized and treated with Na2S2, generated in situ, to give 2,2'-dith iobis[7-C-14]benzoic acid ((5) under bar). The acid chloride from (5) under bar, 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)Clcarbamoyl)phenyldisulfanyl ]-[7-C-14]benzoylamino}-3-methylpentanoic acid ([C-14(2)]CI-1013) ((8) unde r bar). Treatment of (8) under bar with bromine yielded the benzisothiazolo ne, [S-(R*,R*)]-3-Methyl-2-(3-oxo-3H-[3-C-14]benz[d]isothiazol-2-yl)pentano ic acid ([C-14]CI-1012) ((9) under bar).