ORGANIC DISULFIDES AND RELATED SUBSTANCES .42. SYNTHESIS AND PROPERTIES OF SOME TERTIARY DISULFIDES, ESPECIALLY INVOLVING PENICILLAMINE

Five approaches to the synthesis of unsymmetrical tertiary disulfides are illustrated. Penicillamine (1) was thioalkylated with acyclic (2, 4) and cyclic (6) thiosulfonates to give 3, 5, and 7. 5-(Dimethylamino)-l-naphthyl methoxycarbonyl disulfide hydrochloride (12), prepared from the arenesulfonyl chloride (dansyl chloride, 8) via the thiol (9), led to an impure disulfide with N-acetylpenicillamine (13) but to a pure one (17) with a more typical tertiary thiol; the thiol 9 fluoresced more strongly than 8, but the disulfides less so. In an alternative synthetic approach, 13 was used as its thionitrite (18) or thiolsulfonate (22) to thioalkylate a typical primary thiol, reactions that may deserve attention for coupling penicillamine derivatives with protein SH. Several tertiary disulfides resist disproportionation for 24 h in water at 100 °C. When R of RSSCMe2CH(NH2)CO2H was (CH2)2NH3+Cr, however, disproportionation atypically began much more rapidly (4h) than for the amide (24h), and when R was (CH2),SO2Na more rapidly still (1h). © 1979, American Chemical Society. All rights reserved.