Biologically oriented organic sulfur chemistry. 21. Hydrodisulfide of a penicillamine derivative and related compounds

Article abstract of DOI:10.1021/jo00320a030

For study of the chemistry of an amino acid derived hydrodisulfide (10, Me₂C(SR)CH(NHAc)CO₂Me, R = SH), a synthetic route to a hydrodisulfide derivative of N-acetyl-DL-penicillamine was developed. Conversion of N-acetyl-DL-penicillamine (3) to the ester (4, R = H) was accomplished with diazomethane. With acetylsulfenyl chloride, 4 gave the acetyl sulfide (5, R = Ac) instead of the disulfide (7, R = SAc). With (methoxycarbonyl)sulfenyl chloride, 4 gave the corresponding unsymmetrical disulfide (8, R = SCO₂Me), which could not be converted to the hydrodisulfide. Conversion of 4 to the sulfenyl iodide (9, R = I) and treatment with thioacetic acid regenerated 4. With acetyl methoxycarbonyl disulfide, however, 4 gave the acetyl disulfide 7. Methanolysis of 7 then gave the hydrodisulfide 10. Solutions of 10 in chloroform were unchanged after 6 days at room temperature and 1 day at 55°C and then consumed the expected amount of iodine. Washing with bicarbonate led to immediate decomposition; neat 10 completely decomposed during storage at -10°C for 36 h, and the half-life of 10 in HCl-methanol was about 12 h. Treatment of 10 with cyanide ion gave thiocyanate ion, and treatment with 2,4-dinitrochlorobenzene gave a dinitrophenyl derivative [13, R = 2,4-(NO₂)₂C₆H₃S] identical with 13 prepared from 4 by using 2,4-dinitrobenzenesulfenyl chloride.