LTB4, synthesis

Synthesis of LTB4 Synthesis of 20-Hydroxy LTB4 Synthesis of 20-Carboxy LTB4 Synthesis of LTB [(5S, 125 )-DiHete]... 

In more complex systems the nonstabilized Wittig reaction tends to be less reliable in obtaining exclusively cis double bonds. This may be seen in the Merck Frosst LTB4 synthesis (Scheme 2.6), where as much as 20% trans compound is obtained, which must be separated by HPLC. 

Others have demonstrated that hyperoxia altered cultured bovine pulmonary arterial endothelial cells in such a way that they released more 6-keto-PGFjjj and LTB4 upon stimulation with Ca " ionophore. Again it is unclear whether the ultrastructural changes of the endothelial cells (bleb formation, decreased membrane barrier) facilitates influx and LTB4 synthesis or... 

Defects in the pathway of the synthesis of LTB4 has not been reported yet. Since LTB4 is a highly potent chemotactic fector and activator of leucocytes, patients with LTB4 synthesis deficiency are expected to present with recurrent infections and immunological problems in infancy. 

Leukotriene B4, formed by enzymic hydrolysis of LTA4, is chemotactic for macrophages and neutrophils at concentrations as low as 1 ng/ml. The stereochemistry of the conjugated triene subunit was established by synthesis which also made LTB4 available in quantity for biological research. 

Since the stereochemistry of the triene system of LTB4 had not been determined prior to synthesis, a number of stereoisomers of LTB4 were prepared for purposes of definitive comparison of physical properties and bioactivity with biologically produced LTB4. The various stereoisomers of LTB4 were much less active biologically than LTB4 itself. 

Before taking leave of the eicosanoids, 1 need to point out that a second enzyme, 5-lipoxygenase, also metabolizes arachidonic acid. 5-Lipoxygenase initiates the synthesis of the leukotrienes from arachidonic acid. There is a whole family of leukotrienes and these molecules have a spectrum of biological properties. 1 will focus on one important leukotriene, LTB4. 

Figure 4.35 Synthesis of 20,20,20-trifluoroarachidonic acid and its transformation into 20,20,20-trifluoroleukotriene 64 (LTB4) and trifluoro-12-HETE.

A Palauan species of Dysidea contained 15-acetylthioxyfurodysinin lactone (327), that binds to human leukotriene B4 (LTB4) receptor. The structure was determined by spectral data analysis and confirmed by synthesis involving photo-oxidation of 15-acetylthioxyfurodysinin (328), which co-occurs with it in the sponge [297,298]. An Australian species of Euryspongia also contained 15-acetylthioxyfurodysin (329) and 15-acetylthioxyfurodysinin (328) [299]. A sample of D. herbacea from the Great Barrier Reef contained (-)-neodysidenin (330) and the absolute configuration was determined by capillary electrophoresis of Marfey s derivatives [300]. 

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