title: A practical synthesis and biological evaluation of 9-halogenated PGF analogues.
abstract: A series of 9-halo PGF analogues 1-2 and 5-13 were synthesized and biologically evaluated. Among the compounds, 2 was the best EP2-receptor agonist. A practical method of synthesizing 2 via the Julia olefination of an aldehyde 3 with an optically active sulfone 4, which was prepared by Sharpless asymmetric epoxidation of 15, was developed. Other 9-halogenated PGF analogues were synthesized essentially by the same procedure and evaluated. The absolute configuration of 16-OH of 2 was determined as S by the X-ray analysis of a salt consisting of a 1/1 molar ratio of 2 and L-lysine.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. k.tani@ono.co.jp
authors.forename: Kousuke
authors.initials: K
authors.lastname: Tani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganawa
authors.forename: Akiharu
authors.initials: A
authors.lastname: Ishida
authors.forename: Hiromu
authors.initials: H
authors.lastname: Egashira
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Odagaki
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kawanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Sagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Harada
authors.forename: Mikio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohuchida
authors.forename: Kigen
authors.initials: K
authors.lastname: Kondo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000378:metabolism; D006219:Halogens / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D011461:Prostaglandins F, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D006219:Halogens; D011461:Prostaglandins F, Synthetic; D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP