Prostaglandins isolation

Fig. 1. Prostaglandin 1,15-lactones and prostaglandins isolated from Tethys fimbria...

Figure 20.1 Examples of prostaglandins isolated from Alcyonidae and Plexauridae.

Vane and co-workers isolated a new prostaglandin (initially called PGX) from microsomal fraction of stomach. The structure was established by chemical synthesis from PGP2a (Ref. 1). 

The unexpected source of starting material for partial synthesis i)f these agents was the sea. The isolation of 15CR)-PGA2 and its iicetate (44) from the lowly sea whip, Plexura homomalla, one of I he so-called soft corals, made an approach to prostaglandins rrom natural products possible. 

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Lipid (Section 27.1) A naturally occurring substance isolated from cells and tissues by extraction with a nonpolar solvent. Lipids belong to many different structural classes, including fats, terpenes, prostaglandins, and steroids. 

Cooper, C.L. and Malik, K.U. (1985). Prostaglandin synthesis and renal vasoconstriction elicited by adrenergic stimuli are linked to activation of alpha-1 adrenergic receptors in the isolated rat kidney. J. Pharmacol. Exp. Ther. 233, 24-31. 

Ohnishi (Sakamoto etal., 1991) has described an oligomeric derivative of prostaglandin Bi (PGB2) and ascorbic acid. In a rat bilateral carotid occlusion-reperfiision injury complicated by haemorrhagic hypotension, this compound reduced a-phenyl-r-butyl nitrone (PBN) spin-trapped radicals and thiobarbituric acid-reactive products (TBARs) (a measure of lipid peroxidation) in isolated... 

As the first isolable intermediate in the bioconversion of arachidonic acid into prostaglandins and thromboxanes (Eq. 3), PGG2 is a bicyclic peroxide of immense biological importance. It is difficult to obtain pure from natural sources and the presence of the 15-hydroperoxide group adds a further dimension of chemical lability to that associated with the 9,11-peroxide bridge. The chemical synthesis of PGG2 is thus a landmark in prostaglandin chemistry. It also represents a pinnacle of success for the silver-salt route to bicyclic peroxides. 

Studies on the biosynthesis of prostaglandins revealed that a strained bicyclic bis(secondary-alkyl) peroxide was not only a key intermediate, but could survive the biological conditions long enough to be isolated, albeit in minute amounts. This was a startling discovery in that no simple bicyclic peroxides of the same type were known, clearly for reasons of preparative difficulty. The prostaglandin connection focused attention upon this missing class of peroxides and stimulated... 

Pongprayoon U, Baeckstrom P, Jacobsson U, Lindstrom M, Bohlin L. Compounds inhibiting prostaglandin synthesis isolated from Ipomoea pescaprae. Planta Med 1991 57 515-518. 

Additional hypotheses concerning prostaglandin biosynthesis in P. homomalla resulted from isolation of 11R-HETE (76) from the polar lipid fraction [95]. Apparently, 11R-HETE (76) is also a minor product of incubations of arachidonic acid with acetone powder preparations of P. homomalla [95], In this alternate hypothesis (Scheme 8), an 11-hydroxy or 11-hydroperoxy-8,9-allene oxide intermediate is formed from a sequence of oxidations at C8 and Cll. Opening of the allene oxide to a transient C8 earboeation induces eycli-zation with a consequent addition of water to C15. This proposed pathway leads initially to formation of PGE2 (16 or 38), which following acetylation, elimination of acetic acid from Cl 1-12, and esterification, forms the observed major natural product in the coral, 15-acetoxy methyl PGA2 (36 or 54). Notably, if... 

A survey of the ability of various marine invertebrates and their isolated tissues to accumulate prostaglandins from surrounding fluids has led to the speculation that some marine invertebrates may rely on this mechanism to obtain their physiological requirement of prostaglandins [107], It is further speculated that P. homomalla, with its wealth of prostaglandins, may be the ultimate provider of these substances in the Caribbean through release and subsequent uptake by dependent species. 

A guinea pig ileum bioassay was used to detect and aid in the isolation of a smooth-muscle-contracting substance from the Japanese gorgonian coral Euplexaura erecta [108]. This process led to the isolation of prostaglandin F2a (17) from the MeOH extract of the coral. Its identification was based on comparison with authentic PGF2a and its methyl ester by TLC, and comparison with authentic methyl PGF2a trimethylsilyl ether by mass spectrometry. Because of the nature of the techniques employed, some aspects of the stereochemistry in this isolate of PGF2a remain uncertain. 

It has also been shown that the CYP4 family contains a number of natural substrates appear to be arachidonic acid, the prostaglandins, and/or the leukotrienes. For example, CYP4F2 and CYP4F3, isolated from human liver and human leukocytes, respectively, are leukotriene B4 -hydroxylation of arachidonic acid to form 20-hydroxy-5, 8, 11, 14-eicosatetraenoic... 

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