Methyl ethers of prostaglandins F2α and I2

Abstract

Regiospecific monomethyl prostaglandin F₂α ethers (at 0–9, 0–11, and 0–15) have been prepared by total synthesis. The 9,15-bis-ether was also prepared. The 11- and 15-monoethers have been converted to the corresponding prostacyclins. Nuclear Magnetic Resonance (NMR) spectral comparisons indicate conformational changes associated with ether formation; nonetheless, the PGF₂α monoethers all retain significant biological activity: 3–420% of natural PGF₂α. The 9- and 15-methyl ethers show increased selectivity for luteolytic activity as measured in the hamster antifertility (HAF) assay. In contrast the prostacyclin ethers are essentially devoid of agonist activity on both the platelet and vasculature. Prostacyclin diastereomers [5a] also lack activity and it appears that any modification at or of the C-11 or C-15 functions reduces receptor binding by at least a factor of 100.