Synthesis of chemically stable PGI2 analogs II - synthesis of halogen substituted PGI2 analogs

Syntheses of several stable PGI₂ analogs substituted by halogen atoms(s) at C-5 or(and) C-7 are described. Reaction of protected PGI₂ methyl ester ( ) with -chlorosuccinimide gave 5-chloro-Δ⁶-PGI₁ derivative ( ), which was transformed into 5-chloro- and 5,7-dichloro-PGI₂ ( ) and ( )] by subsequent isomerization or chlorination. Similarly, reaction of with -bromosuccinimide gave 5-bromo-Δ⁶-PGI₁ derivative ( ), which was further transformed into 7-fluoro-PGI₂ ( ) by silver fluoride treatment. These halogenated PGI₂ analogs were found to be much more stable than PGI₂.