N-Chloroazasteroids: A Novel Class of Reactive Steroid Analogues. Preparation, Reaction with Thiols, and Photochemical Conversion to Electrophilic N-Acyl Imines

Article abstract of DOI:10.1021/jo00269a029

N-Chloroazasteroids 2, 5, 7, 10, 12, 15, 18, and 22 were easily prepared by the reaction of N-chlorosuccinimide with the parent azasteroid lactams 1, 4, 6, 9, 11, 14, 17, and 21, respectively.The products reacted with the model thiols benzenethiol and L-cysteine ethyl ester to afford the corresponding N-thiolactams 3, 8, 13, 16, and 23, as well as the parent lactams and disulfides, via sulfenyl chloride intermediates.The reaction of benzenethiol with N-chloro-17β-hydroxy-4-aza-3-androstanone (2) resulted in anomalous formation of the stable sulfenate and sulfinateesters 24a and 24b.Photolyses of N-chloroazasteroids in methanol resulted in the formation of enamides 27, 28, and 30, or the carbinol amido methyl ethers 32 and 34.These products were formed by the isomerization or solvent trapping of reactive N-acyl imine intermediates.The ability of N-chloroazasteroids to react covalently with thiols and to generate electrophilic N-acyl imines suggests potential biological applications in affinity labeling and enzyme inhibition and for use as antihormonal agents.