Synthesis and biological properties of gem-difluorinated prostaglandin derivatives


Yoshitomi Morizawa,, Takashi Nakano1, Nobuaki Mori2, and Yasushi Matsumura3. (1) Research Center, Asahi Glass Co., Ltd, 1150 Hazawa-cho, Kanagawa-ku, Yokohama, 221-8755, Japan, (2) Chemicals Company, Asahi Glass Co., Ltd, 1-12-1, Yurakucho, Chiyoda-ku, Tokyo, 100-8405, Japan, (3) Fine Chemicals Group, Chemicals Company, Asahi Glass Co., Ltd, 10 Goikaigan, Ichihara, 290-8586, Japan
Synthesis of novel 7,7-difluoroprostaglandin (PG) I2 (1) and 15-deoxy-15,15-difluoro PG F2alpha (2) derivatives will be presented. Two fluorine atoms were introduced by electrophilic fluorination of Corey lactone enolates with the N-fluorobenzenesulfonimide reagent in the presence of manganese salt for the synthesis of 1 as a one pot reaction. The analogue 1 showed very high stability against hydrolysis and selectivity for the prostacyclin receptor. The difluoro analogue of PGF2alpha derivative (2) was synthesized via geminal difluorination of the enone derived from Corey aldehyde with morpholinosulfur trifluoride. The obtained compound 2 exhibited high affinity for the prostaglandin receptor.