FTIR spectral study of intramolecular hydrogen bonding in E-type of 15-keto-prostaglandins in dilute CCl4 solution: structure-activity relationships.
FTIR spectra of 15-keto-prostaglandin (PG)E2 (1), 15-keto-PGE1 (2), 13,14-dihydro-15-keto-PGE2 (3), 13,14-dihydro-15-keto-PGE1 (4), and their related compounds were measured in dilute tetrachloromethane solution in order to examine the structure-activity relationships for the 5,6-cis-double bond of the alpha-side chain and the 13,14-trans-double bond and the 15-hydroxyl group of the omega-side chain in PGE2, PGD2, and PGF2 alpha. The spectra were subjected to curve analysis to separate overlapping absorption bands. For compounds 1-4, an intramolecular hydrogen bond involving a 15-membered ring similar to that observed for PGE2, PGD2, and PGF2 alpha was found between the carboxyl and 15-carbonyl groups. The percentages (rho) of the intramolecular hydrogen-bonded molecules with the 15-membered rings in 1-4 and PGE2 were compared with the known binding activities of PGs for various PG receptors, and we found that these activities decrease as the rho values decrease. These results strongly supported our hypothesis that, in PGs, the conformation with the 15-membered ring formed by the intramolecular hydrogen bonds between the carboxyl group of the alpha-side chain and the 15-hydroxyl group of the omega-side chain is a precursory conformation of the active one.
Takasuka
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Yamakawa
M
M
D000527:Alprostadil / Q000031:analogs & derivatives / Q000737:chemistry; D002251:Carbon Tetrachloride / Q000737:chemistry; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D008968:Molecular Conformation; D011454:Prostaglandins A / Q000737:chemistry; D011458:Prostaglandins E / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013229:Stearic Acids / Q000737:chemistry; D013329:Structure-Activity Relationship
D011454:Prostaglandins A; D011458:Prostaglandins E; D012996:Solutions; D013229:Stearic Acids; C098204:12-oxooctadecanoic acid; D006859:Hydrogen; D002251:Carbon Tetrachloride; D000527:Alprostadil; D015232:Dinoprostone