Kinetics of electrophilic fluorination of steroids and epimerisation of fluorosteroids

Rozatian, Neshat; Harsanyi, Antal; Murray, Ben J.; Hampton, Alexander S.; Chin, Emily J.; Cook, Alexander S.; Hodgson, David R.W.; Sandford, Graham

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, we conducted kinetics studies on enol ester derivatives of progesterone, testosterone, cholestenone and hydrocortisone with a series of electrophilic N−F reagents. We explored the stereoselectivities of fluorination reactions of progesterone enol acetate and the kinetic effects of additives, including methanol and water. The kinetics of epimerisation of 6β‐fluoroprogesterone to the more pharmacologically active 6α‐fluoroprogesterone isomer in HCl/acetic acid solutions are detailed.

Citation

Rozatian, N., Harsanyi, A., Murray, B. J., Hampton, A. S., Chin, E. J., Cook, A. S., Hodgson, D. R., & Sandford, G. (2020). Kinetics of electrophilic fluorination of steroids and epimerisation of fluorosteroids. Chemistry - A European Journal, 26(52), 12027-12035. https://doi.org/10.1002/chem.202001120

• Journal Article Type: Article
• Acceptance Date: Apr 8, 2020
• Online Publication Date: Aug 25, 2020
• Publication Date: 2020-09
• Deposit Date: Apr 2, 2020
• Publicly Available Date: Sep 18, 2020
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 52
• Pages: 12027-12035
• DOI: https://doi.org/10.1002/chem.202001120
• Public URL: https://durham-repository.worktribe.com/output/1273551