Prostaglandin hydroxyl position

First, the chemical difference between the ring structures of PGE and PGF prostaglandins is that in PGE there is a keto group at position 9, whilst in PGF this position is taken up by a hydroxyl (secondary alcohol) group. 

Prostaglandins (= PG) constitute a class of hormones that are present in almost all human tissues and fluids in minute concentrations and are thought to play a dominant role in the control of pregnancy, hypertension, ulcers, asthma, and pain. Since they may be useful as pharmaceuticals, several total syntheses were developed, and the term to, prostaglandize a class of compounds, which means to exhaust its synthetic potentials, has become known. The principal structures of prostaglandins are shown below. The capital letters A,B,C,E,F denote the state of oxidation and the position of double bonds in the cyclopentane or cyclopentene ring the numeral subscript refers to the number of double bonds in the side-chains 1 = (trans)-13 2 (cis,trans)-6,13 3 = (cis,trans,cis)-6,13,17 a( = below) and fi( = above) indicate the position of the hydroxyl group on C-9. 

The anti-inflammatory activity of curcumin and its derivatives is associated with the hydroxyl and phenol groups in the molecule, which are also essential for the inhibition of prostaglandins, PG synthetase and leucotriene synthesis (LT) (Kiuchi et al., 1982, 1992 Iwakami, et al, 1986). Claeson et al. (1993, 1996) suggested that the antiinflammatory action and the antiparasitic activity were associated with the (3-dicarbo-nylic system with conjugated double bonds (dienes) (Araujo et al., 1998, 1999). The better skin penetration and lipophylicity is attributed to the presence of a diene ketone system. Calebin-A, a novel curcuminoid isolated from turmeric, protects neuronal cells from (3-amyloid insult. The hydroxy group at para-position of this compound is most critical for the expression of biological activity (Kim et al., 2001). 

A key intermediate, 28, of prostaglandin synthesis can be prepared by a stereospecific hydroxylation. Aspergillus niger ATCC 9142 introduces the oxygen function into the prostaglandin precursor 27 at the required position, producing the (/ )-alcohol in 67% yield and 36% ee371. 

Figure 6-16. Prostaglandins, thromboxanes, and leukotrienes. For each of the classes of prostaglandins (H, E, F, A), the ring contains hydroxyl and keto groups at different positions. Only the ring portions of PGE2, PGF2ct, and PGA2 are shown. The remainder of the molecule (not shown) is the same as PGH2. The subscript refers to the number of double bonds in the nonring portion. The class with two double bonds is derived from arachido-nate. Other classes (with one or three double bonds) are derived from other polyunsaturated fatty acids.

Arachidonic acid, which is stored as a cellular membrane phospholipid, is the precursor for series 2 prostaglandins. Aspir in selectively acetylates the hydroxyl group of a single serine residue at position 530 within the polypeptide chain of prostaglandin G/H synthase, the enzyme that converts arachidonate into prostaglandin cyclic endoperoxide. Aspirin thereby reduces the synthesis of the eicosanoids— prostaglandins, prostacyclin, and thromboxane A. 

They convert cholesterol to bile acids and convert vitamin prostaglandins, and many other metabolites to more soluble and often biologically more active forms. In plants cytochromes P450 participate in hydroxylation of fatty acids at many positions. ... 

F. 35.6. Prostaglandins of the 1-, 2-, and 3-series and their precursors. The numeral (as a subscript in the name of the compound) refers to the number of double bonds in the non-ring portion of the prostaglandin. Trans double bonds are at position 13, and cis double bonds at positions 5 and 17. The hydroxyl group at carbon 15 is required for biologic activity. 

Ene reaction of 680 at 290°C gave the same products, but in a ratio of 2 7 40.497 Good selectivity is possible in the ene reaction, as in the conversion of 684 to 685 in 60% yield at 250°C, in Stork s explorations toward the synthesis of prostaglandins.498 in this case, the silyl group on the secondary hydroxyl was selectively removed by treatment with dilute HCl in THE (sec. 7.3.A.i). This selectivity may be due to increased steric hindrance at that position or to a rate-determining oxygen protonation step, or both.498... 

Fatty Acid u-Hydroxylase - Fatty acids, including prostaglandins, leukotrienes, and other arachidonic acid derivatives, are hydroxylated at the (jj-position by a cytochrome P-450 isozyme that, at least for some fatty acids, is induced by clofibrate but not by classical cytochrome P-450... 

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