Photochemistry of clobetasol propionate, a steroidal anti- inflammatory drug

Abstract

The photochemistry of the anti-inflammatory drug clobetasol propionate 1 was studied in aerobic as well as in anaerobic condition with different irradiation wavelengths (254 nm and 310 nm) in acetonitrile and 2-propanol. Photoproducts obtained were isolated and characterized on the basis of IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The products were: 21-chloro-9-fluoro-11-hydroxy-16-methyl-17(1-oxopropoxy)-1,5- cyclopregn-3-ene-2,20-dione 2 (254 nm), 21-chloro-9-fluoro-11-hydroxy-16-methyl- 17(1-oxopropoxy)-18,20-cyclopregn-1,4-diene-3-one 3 (310 nm/2-propanol, argon), 9-fluoro-17-hydroperoxy-16-methyl-17(1-oxopropoxy)androsta-1,4-diene-3-one 4 (310 nm/O2/2-propanol). Cyclohexadienone moiety in ring A and keto group at C17 were found to be deeply modified by U.V light and therefore loss of biological activity during storage and in vivo cannot be ruled out. ©ARKAT.