Prostaglandins partial synthesis

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. 

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. 

The first prostaglandins were prepared by partial synthesis. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

The special potential for constructing double bonds stereoselectively, often necessary in natural material syntheses, makes the Wittig reaction a valuable alternative compared to partial hydrogenation of acetylenes. It is used in the synthesis of carotenoids, fragrance and aroma compounds, terpenes, steroides, hormones, prostaglandins, pheromones, fatty acid derivatives, plant substances, and a variety of other olefinic naturally occurring compounds. Because of the considerable volume of this topic we would like to consider only selected paths of the synthesis of natural compounds in the following sections and to restrict it to reactions of phosphoranes (ylides) only. 

Tada M, Esumi K, Yamageshi M et al. (1984) Reduction of prostaglandin synthesis as a possible cause of transient flow reduction in a partially constricted canine coronary artery. Mol Cell Biol 16 1137-1149 Uchida Y, Yoshimoto N, Murao S (1975) Cyclic fluctuations in coronary blood pressure and flow induced by coronary artery constriction. Jpn Heart J 16 454—464 Warltier DC, Lamping KA, Pelc LR, Gross GJ (1987) A canine model of thrombin-induced coronary artery thrombosis Effects of intracoronary streptokinase on regional myocardial blood flow, contractile function, and infarct size. J Pharmacol Meth 18 305-318... 

As mentioned, prostaglandins stimulate the inflammatory response and, as a result, are partially responsible for the cascade of events that cause pain. Aspirin has long been known to alleviate such pain, and we now know that it does so by inhibiting the synthesis of prostaglandins (Figure 18.5). 

Some, but not all the evidence suggests that prostaglandins may be involved in the hypotensive action of ACE inhibitors, and that aspirin, by inhibiting prostaglandin synthesis, may partially antagonise the effect of ACE inhibitors on blood pressure. This effect appears to depend on the... 

The increase in lung vascular permeability by bacteria and endotoxins [366,367] is augmented by inhibition of prostaglandin synthesis [368]. Some of the increased permeability demonstrated under clinical and experimental conditions may be due to histamine release, but since H, antagonists only partially inhibit the increase, other factors have to be considered [369]. 

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