Prostaglandin 15-hydroxy

This enzyme [EC 1.1.1.50], also referred to as hydroxy-prostaglandin dehydrogenase, catalyzes the reaction of androsterone with NAD(P)+ to produce 5a-androstane-3,17-dione and NAD(P)H. Other 3a-hydroxysteroids can act as substrates as well as 9-, 11- and 15-hydroxy-prostaglandins. The stereochemistry is B-specific with respect to the pyridine coenzymes. 

Anggard, E, Larsson, C and Samuelsson, B (1971) The distributation of 15-hydroxy prostaglandin A -reductase in the tissue of swine. Acta Physiol Scand, 240, 3518-3521. 

It should be noted that the various 15-deoxy-16-hydroxy-prostaglandins prepared in the course of our studies consisted of two racemates ( 1 1 by NMR) epimeric at Cje which were not separable by TLC or HPLC. However, introduction of an allylic double bond (A or 16-vinyl) frequently made separation feasible. A 17-methyl group (4 racemates) also allowed separation into two components. Of necessity, the compounds were tested as the racemic mixture, although it is likely that biological activity largely resides with only one of the four diastereomers (40.56). 

The only other bronchodilator information available concerning this series of carboxylic acid equivalents is a report that PGEj and other carbinols (XV) (50,51) and 15-deoxy-16-hydroxy-prostaglandin carbinols will relax ginea pig trachea (131a). 

Subsequent oxidation of 20-hydroxy prostaglandins may lead to the formation of aldehyde compounds [314] and finally to w-carboxylic metabolites [261-263,269,271,272,274,275]. After this step has taken place, one or two steps of y8-oxidation can take place also from this end of the prostaglandin molecule [265,271,275-277]. Thus, several highly degraded prostaglandin metabolites have been identified in human [275-277] and rat urine [265] C,4 compounds which are generally tetranor, w-dinor dicarboxylic acids but in one case a dinor, co-tetranor dioic compound [276]. 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Tris( Hydroxy methyl jaminomethane Prostaglandin F2ct... 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

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