Prostanoids structures

Blair, I.A., Hensby, C.N. and MacDermot, J. (1980). Prostacyclin-dependent activation of adenylate cyclase in a neuronal somatic cell hybrid prostanoid structure-activity relationships. Br. ]. Pharmacol, 69, 519-525... 

The PGFjj receptor of ovine and bovine corpus luteum has been studied by Hammarstrom, Powell, Rao and their co-workers . There is a clear parallel between the abilities of a large number of prostanoid structural analogues to cause luteolysis and to bind luteal membrane preparations ... 

Fig. 1. Biosynthesis of prostanoids, where structures (5)—(8) are PGG2, PGH2, PGD2, and PGF2Q, respectively.

The organization of Part Two is according to structural type. The first section, Chapter Seven, is concerned with the synthesis of macrocyclic compounds. Syntheses of a number of heterocyclic target structures appear in Chapter Eight. Sesquiterpenoids and polycyclic higher isoprenoids are dealt with in Chapters Nine and Ten, respectively. The remainder of Part Two describes syntheses of prostanoids (Chapter Eleven) and biologically active acyclic polyenes including leukotrienes and other eicosanoids (Chapter Twelve). 

Drugs of particularly complex structure are often prepared commercially by partial synthesis from some abundant, structurally related, natural product obtained from plants. The majority i)f steroid drugs are in fact prepared in just this way. Prostaglandins are unique in that no prostanoid compounds have yet been found in plants, a perhaps surprising finding in view of the wide distribution of essential fatty acids in plant materials. 

More recently, the prostanoid metabolites of P. homomalla have been reinvestigated relative to their potential natural function [69], A minor new metabolite was isolated and characterized in this work by high field NMR studies. Its structure, the 9-O-acetate of methyl PGF2ar (55), seems secure given the opportunity to compare H and 13C NMR data sets with an earlier isolate of the 11-O-acetate of PGF2c( (56) [70],... 

Investigations of the natural products chemistry of the Red Sea soft coral Lobophyton depressum (Alcyonacea) led to the isolation of a crystalline prostanoid derivative [70]. On the basis of H NMR data, the planar structure was developed as methyl ll-acetoxy-PGF2tt (56). Stereochemistry at Cl5 was established as S by comparison of the biological and NMR features of the hydrolyzed... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

In this chapter, the recent development of the fluorinated prostanoids, which take advantage of the unique properties caused by fluorine atoms, was introduced. It is remarkable that a subtle change in structures of a series of compounds markedly... 

Triclavulone 3, recently isolated from Ciavularia vulgaris, is one of the most complex of the family of about forty structurally-related fatty acid-derived marine prostanoids described from this species. Hisanaka Ito and Kazuo Iguchi of the Tokyo University of Pharmacy and Life Science recently reported (J. Am. Chem. Soc. 2004,126,4520) the total synthesis of 3, starting with the preparation of the enantiomerically-enriched bicyclic ketone 1. 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

Watanabe K, Sekine M, Iguchi K (2003) Isolation and Structures of New Halogenated Prostanoids from the Okinawan Soft Coral Clavularia viridis. J Nat Prod 66 1434... 

Coleman R. A., Smith W. L., andNarumiya S. (1994). International Union of Pharmacology classification of prostanoid receptors properties, distribution, and structure of the receptors and their subtypes. Pharmacol. Rev. 46 205-229. 

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