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Kinetics of Electrophilic Fluorination of Steroids and Epimerisation of Fluorosteroids
Author(s) -
Rozatian Neshat,
Harsanyi Antal,
Murray Ben J.,
Hampton Alexander S.,
Chin Emily J.,
Cook Alexander S.,
Hodgson David R. W.,
Sandford Graham
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001120
Subject(s) - electrophile , enol , kinetics , chemistry , reagent , methanol , acetic acid , organic chemistry , electrophilic fluorination , steroid , medicinal chemistry , catalysis , biochemistry , physics , quantum mechanics , hormone
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.