Prostaglandins, 19-Hydroxylated

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

The p-phenylbenzoate ester was prepared to protect the hydroxyl group of a prostaglandin intermediate by reaction with the benzoyl chloride (Pyr, 25°, 1 h, 97% yield). It was a more ciystalline, more readily separated derivative than 15 other esters that were investigated. It can be cleaved with K2CO3 in MeOH in the presence of a lactone. ... 

In a prostaglandin synthesis a carbonyl group was protected as an oxime in which the hydroxyl group was protected against Collins oxidation by the phenylthiome-thyl-group. The phenylthiomethyl group is readily removed to give an oxime that is then cleaved to the carbonyl compound. ... 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

Butaprost (82) not only has the typical C-15 hydroxyl of the natural prostaglandins moved to C-16, as do several of the analogues discussed above, but it has a rather interesting gem dialkyl substitution at C-17, presumably for metabolic protection, in the form of a cyclobutyl ring. It is a bronchodilator and is prepared in a manner analogous to that of rioprostil discussed above [17]. 

Prostaglandin F, a hormone that causes uterine contraction during childbirth, has the following structure. Are the two hydroxyl groups (-OH) on the cyclopentane ring cis or trans to each other What about the two carbon chains attached to the ring ... 

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. 

This compound has not been previously reported in the literature. The compound is unusual In that the substitution pattern of alkyl and hydroxyl groups on the ring Is analogous to the prostaglandin F series. 

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... 

The analogue in which carbon replaces oxygen in the enol ring should of course avoid the stability problem. The synthesis of this compound initially follows a scheme similar to that pioneered by the Corey group. Thus, acylation of the ester (7-2) with the anion from trimethyl phosphonate yields the activated phosphonate (7-3). Reaction of the yhde from that intermediate with the lactone (7-4) leads to a compound (7-5) that incorporates the lower side chain of natural prostaglandins. This is then taken on to lactone (7-6) by sequential reduction by means of zinc borohydride, removal of the biphenyl ester by saponification, and protection of the hydroxyl groups as tetrahydropyranyl ethers. 

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