Kinetics of Electrophilic Fluorination of Steroids and Epimerisation of Fluorosteroids |
| |
Authors: | Dr Neshat Rozatian Dr Antal Harsanyi Ben J Murray Alexander S Hampton Emily J Chin Alexander S Cook Dr David R W Hodgson Prof Graham Sandford |
| |
Affiliation: | Chemistry Department, Durham University, South Road, Durham, DH1 3LE UK |
| |
Abstract: | Fluorinated steroids, which are synthesised by electrophilic fluorination, form a significant proportion of marketed pharmaceuticals. To gain quantitative information on fluorination at the 6-position of steroids, kinetics studies were conducted on enol ester derivatives of progesterone, testosterone, cholestenone and hydrocortisone with a series of electrophilic N?F reagents. The stereoselectivities of fluorination reactions of progesterone enol acetate and the kinetic effects of additives, including methanol and water, were investigated. The kinetics of epimerisation of 6β-fluoroprogesterone to the more pharmacologically active 6α-fluoroprogesterone isomer in HCl/acetic acid solutions are detailed. |
| |
Keywords: | epimerisation fluorination fluorosteroid kinetics stereoselectivity |
|
|