Study of substitution reaction on ring a of estradiol

Abstract

Estradiol-conjugated anticancer drugs are the effective strategy that could specifically combat breast cancer cells, while minimizing the toxicity of the drug toward normal cells. Estradiol has been previously conjugated with drugs mostly at rings B, C and D. Functionalizations at ring A of estradiol introduce new types of conjugated drugs that could improve both the selectivity and efficiency in binding with estrogen receptor (ER). Using 4-cresol as the model, the nitration at meta-position was achieved, although with unsatisfied result of only 6% overall yield of the product. The practical results derived from diazo coupling on ortho-position of 4-cresol, which led to successful functionalizations at 2- or 4-positions of estradiol. The diazo estradiol was reduced, conjugated with dicarbonyl derivatives, which was a conjugated anticancer drug converted to a conjugated hydroxamic acid that dovely resembles suberanilohydroxamic acid (SAHA).