Biomimetic synthesis of hemiketal eicosanoids for biological testing.

The hemiketal (HK) eicosanoids HKE2 and HKD2 are the major products resulting from the biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways. They are formed by activated human leukocytes ex vivo, and, therefore, may be involved in regulation of the inflammatory response as autocrine or paracrine mediators. HKE2 and HKD2 are not commercially available and, so far, no method for their total chemical synthesis has been reported. The limited availability has impeded the characterization of their biological effects. Here, we describe a method for biomimetic preparation of HKE2 and HKD2 by reaction of recombinant human cyclooxygenase-2 with chemically synthesized 5S-HETE. We found that HKE2 did not induce or inhibit the release of TNFα and IL-1β by human THP-1 monocytes and phorbol ester treatment-derived macrophages.