Prostaglandins E3 and

The third family of prostaglandins, based on the marine fatty acid precursor eicosapentaenoic acid, was synthesized with the help of a number of new methods designed for the introduction of the doubly unsaturated omega chain. 

The y-appendage of the PGy s can also be generated by the following methods (Ref. 3). Method 1  

The chiral keto acid A could be obtained by resolution with (5)-(-)-a-methylben2ylamine. Another route from A to PC s is shown below  

Total Synthesis of Prostaglandin A2 and Conversion to Other Prostaglandins 

Conversion of PGA2 to PGE2, PGF2 and PGEj, PGFj (Ref. 7)  

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A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

Kulkarni PS, Srinivasan BD. Prostaglandins E3 and D3 lower intraocular pressure. Invest. Ophthalmol. Vis. Sci. 1985 26 1178. 

The a-hnolenic acid derivatives EPA and DHA are found as structural components of brain and retinal tissue phosphohpids and as precursors of the triene prostaglandins. DHA is a component of human cerebral cortex, retina, and muscle [23]. EPA is the immediate precursor of prostaglandin E3, thromboxan A3, and prostacyclin 13. Only a small amount of exogenously administered a-linolenic acid is metabolized to these two acids. In particular EPA is ingested for the most part preformed in dietary fish oils [13, 24]. TTie slow conversion of a-linolenic acid to the longer derivatives exhibits a specie importance of EPA and DHA supplementation. 

Bell JG, Tocher DR, MacDonald FM, Sargent JR. Diets rich in eicosapentaenoic acid and gamma-linolenic acid affect phospholipid fatty acid composition and production of prostaglandins El, E2, and E3 in turbot (Scophthalmus maximus), a species deficient in delta 5 fatty acid desaturase. Prostagland Leukotr Essent Fatty Acids 1995 53 279-86. 

Prostaglandins occur in a wide variety of animal tissues and there are a number of instances where they are released on tissue stimulation or activation. Human seminal fluid is the richest source where thirteen different members of the series have been identified (Ej, E2, E3, Fi F2 Ai, A2, Bi, B2 and 19-OH Ai, A2, Bj and B2) with a total concentration of about 300 ng/ml [22, 23]. Considerable species variation is exhibited both in the number and concentration thus only five of these thirteen [24] are found in ram semen and that of some other species contains none at all [5]. The ram vesicular gland is an important source of prostaglandins and the enzyme system from this organ is used for laboratory synthesis starting from added fatty acid precursors [25]. 

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