A practical synthesis and biological evaluation of 9-halogenated PGF analogues.
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.
Tani
Kousuke
K
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. k.tani@ono.co.jp
Naganawa
Atsushi
A
Ishida
Akiharu
A
Egashira
Hiromu
H
Odagaki
Yoshihiko
Y
Miyazaki
Toru
T
Hasegawa
Tomoyuki
T
Kawanaka
Yasufumi
Y
Sagawa
Kenji
K
Harada
Hiroyuki
H
Ogawa
Mikio
M
Maruyama
Takayuki
T
Nakai
Hisao
H
Ohuchida
Shuichi
S
Kondo
Kigen
K
Toda
Masaaki
M
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
D006219:Halogens; D011461:Prostaglandins F, Synthetic; D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP