PGF derivatives

The partial or full structures given above indicate the following difnculties which one has to face in synthesis of pharmacologically interesting PGE and PGF derivatives ... 

Subsequent dehydrohalogenation afforded exclusively the desired (Z)-olefin of the PGI2 methyl ester. Conversion to the sodium salt was achieved by treatment with sodium hydroxide. The sodium salt is crystalline and, when protected from atmospheric moisture and carbon dioxide, is indefinitely stable. A variation of this synthesis started with a C-5 acetylenic PGF derivative and used a mercury salt cataly2ed cyclization reaction (219). Although natural PGI has not been identified, the syntheses of both (6R)- and (65)-PGl2, [62777-90-6] and [62770-60-7], respectively, have been described, as has that of PGI3 (104,216). 

R = H) gave the 155 alcohol (60, R = H) exclusively, but in 40% isolated yield. Reduction of the monocyclic enone 61 under the standard reduction conditions gave the PGF derivative 62 as a single stereoisomer in 76% isolated yield (eq. [23]). 

PGE and PGF derivatives lower intraocular pressure. The mechanism of this action is unclear but probably involves increased outflow of aqueous humor from the anterior chamber via the uveoscleral pathway (see Clinical Pharmacology of Eicosanoids). 

On the way to 7-oxa-PGE,123) starting with the same all-c -l,2-epoxycyclo-pentane-3,5-dio 27 as used for the synthesis of 7-oxa-PGF-derivatives, Fried and co-workers utilized some unusual selective reactivity of polyhydroxylated cyclopentanes. 

Ophthalmology Latanoprost, a PGF, derivative, is used for the treatment of glaucoma. Unoprostone is a newer related drug. These agents apparendy increase the outflow of aqueous humor, thus reducing intraocular pressure. 

This shift of 6 amu indicates that the biosynthetically prepared H2-"6-oxo PGF only contains 6 deuterium atoms and has already lost a labile deuterium atom during its preparation. The El mass spectrum of the H2 6-oxo PGF derivative (not shown) further confirms this conclusion the highest mass ion is at m/z 614, which is due to the loss of a CHgO -moiety and which again corresponds with a shift of 6 amu. Loss of label from biosynthetically prepared deuteri urn-labeled prostaglandins has been described for PGD2, where loss of deuterium occurs at the 12-position(12, 13),... 

Carmely, S., Y. Kashman, Y. Loya, and Y. Benayahu New Prostaglandin (PGF) Derivatives from the Soft Coral Lobophyton depressum. Tetrahedron Lett. 21, 875 (1980). 

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