Stabilization of a prostaglandin tertiary allylic alcohol system by fluorine: synthesis, acid stability studies and pharmacology of a 16-fluoromethyl analog of SC-46275.

Abstract The synthesis of a 16-fluoromethyl analog of SC-46275, a potent, long-acting and selective analog of enisoprost, is described. Introduction of a fluorine atom to the C-16 methyl group of SC-46275 conveys a remarkable increase in stability toward acid induced epimerization, dehydration and allylic rearrangement while having minimal influence on the pharmacological profile. The synthesis of a 16-fluoromethyl analog of SC-46275, a potent, long-acting and selective analog of enisoprost, is described. Introduction of a fluorine atom to the C-16 methyl group of SC-46275 conveys a remarkable increase in stability toward acid induced epimerization, dehydration and allylic rearrangement while having minimal influence on the pharmacological profile.