Revising the structure of a new eicosanoid from human platelets to 8,9-11,12-diepoxy-13-hydroxyeicosadienoic acid.

Eicosanoids are critical mediators of fever, pain, and inflammation generated by immune and tissue cells. We recently described a new bioactive eicosanoid generated by cyclooxygenase-1 (COX-1) turnover during platelet activation that can stimulate human neutrophil integrin expression. On the basis of mass spectrometry (MS/MS and MS), stable isotope labeling, and GC-MS analysis, we previously proposed a structure of 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (DXA).

Synthesis of 15R-PGD2: a potential DP2 receptor agonist.

The first total synthesis of 15R-PGD(2)3 was accomplished. The approach used in this report is also an efficient method to produce 15R-PGE(2). 15R-PGD(2), a potential DP(2) receptor agonist, could be an important novel tool for defining the role of this receptor in inflammatory diseases.

The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP receptor agonist.

Using human and bovine corneal tissue, we investigated the in vitro metabolism of bimatoprost (17-phenyl-18,19,20-trinor-prostaglandin F(2alpha) ethyl amide, Lumigan (Allergan, Inc, Irvine, CA). Enzymatic amidase activity, which converts bimatoprost to the corresponding prostaglandin carboxylic acid, was found to be present in corneal tissue from both species. Using HPLC and mass spectrometry for analyses, conversion of bimatoprost to 17-phenyl-18,19,20-trinor prostaglandin F(2alpha) continued for at least 24 hours after excision of the cornea, with a conversion rate of approximately 25 microg/24 hours.