Prostanoids synthesis

Acetaminophen is a weak inhibitor of peripheral COX. Its analgesic effects may arise from inhibition of prostanoid synthesis in the CNS or other centrally mediated effects yet to be elucidated. The antipyretic ef-... 

A review of neighbouring-group effects in natural products includes steroidal examples. The 19-acetoxy-5a-bromo-6-oxo-steroids (228) fragment with base to give the 6-oxo-A -compounds (229) which are regarded as potentially useful intermediates in prostanoid synthesis.The preparation and properties of the 6-spirocyclopropane (230) have been reported. Attempts to cleave the cyclopropane symmetrically were unsuccessful although other cleavages are discussed. ... 

Henriksson P, Blomback M, Bratt G, Edhag O, Eriksson A, Vesterqvist O. Effects of oestrogen therapy and orchidectomy on coagulation and prostanoid synthesis in patients with prostatic cancer. Med Oncol Tumor Pharmacother 1989 6(3) 219-25. 

There are at least two different types of COX, COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 (which is constitntive) this leads to an inhibition of prostanoid synthesis, and reduced levels of PGE2 in particular lead to an increase in gastric acid production (Chapter 4), as weU as a reduction in mucous secretion. Aspirin also modifies the enzymatic activity of COX-2 (which is inducible) normally COX-2 produces prostanoids, most of which are pro-inflammatory, but aspirin-modified COX-2 produces lipoxins, which are anti-inflammatory. 

Prostaglandin endoperoxide H2 synthase (PGHS) [EC 1.14.99.1] isoenzymes 1 and 2 catalyze the committed step in prostanoid synthesis via two sequential enzymatic reactions... 

Chiral synthesis of a prostanoid.Trost etal. have devised an enantioconvergent prostanoid synthesis from 1, in which a 1,3-hydroxy shift interconverts the two enantiomers. The interconversion was possible by equilibration of the urethane of 1 with (S)-l-o -naphthylethylamine catalyzed with mercury(II) trifluoroacetate (7, 382). At equilibrium the ratio of 2a/2b is about 1 3. By separation and repeated... 

HANSCH GM, GEMSA D, RESCH K. Induction of prostanoid synthesis in human platelets by the late complement components CSb-9 and the channel forming antibiotic nystatin inhibition of the recyclation of liberated arachidonic acid. J Immunol 135 1320-1324,1986. 

Because aspirin blocks prostanoid synthesis, the ability of aspirin to impair platelet... 

Levi G, Minghetti L, Aloisi F (1998) Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. Biochimie 80 899-904. 

Intraperitoneal administration of coptisine at dosages of 0.5, 1, and 5 mg/kg/day to original-type anti-GBM-induced nephritic rats was shown to be effective in the inhibition of urinary protein excretion, elevation of serum cholesterol, and creatinine contents, as well glomerular histopathological changes. The alkaloid inhibited platelet aggregation in both in vitro and in vivo assays. These results suggest that the antinephritic effect of coptisine may be due partly to antiplatelet action and improved renal hemodynamics, via the alteration of prostanoid synthesis [223]. 

Arachidonic acid, liberated from membrane phospholipids, can be metabolized to the five primary prostanoids, PGDg, PGE2, PGF2 , PGI and TXAg. The fet two steps in this process are catalyzed by the cyclooj gen-ase (COX) enzymes and thereafter by specific prostanoid synthases (32). An overview of prostanoid synthesis is illustrated in Fig. 6.2. 

With the phenomenon established, a strategy for prostanoid synthesis emerges as shown in equation 3. In the major simplifi-... 

---