Synthesis of Estradiol-Cinnamide Conjugates

Abstract

The synthesis of a number of structurally related estradiol-17α-ylmethyl hydroxycinnamides and of one novel estra-1,3,5(10),6-tetraen-3-ol-17β-yl hydroxycinnamide is described, using a microwave assisted amidation of steroidal amines with pentafluorophenol activated, non-protected hydroxycinnamic acids as a key step. A selection of the compounds and of other estra-1,3,5(10)-trien-3-ol 17β-yl hydroxycinnamides was screened against 60 human cancer cell lines, derived from nine neoplastic diseases. From the overall results of the screening, it could be inferred that dihydroxycinnamide derived estradiol conjugates exhibit a better cytotoxic profile when compared with hydroxymethoxycinnamide derived estradiol conjugates.

Reduction of Oximes and Hydrazones: Asymmetric and Diastereoselective Approaches

“…Optically active steroidal amine 123 was obtained in moderate yield (46%) as a single diastereoisomer, through the reduction of oxime 122 with aluminium amalgam (Al/HgCl2) in refluxing ethanol/water after 24 h. This methodology was successful in the selective reduction of the oxime while maintaining the double bond at the 6-position. However, due to the poisonous nature of the mercury (II) salts, it is rarely used nowadays [92]. Scheme 29.…”