Alan E. Barton

Synthesis of three potential inhibitors of the biosynthesis of leukotrienes A–E

Abstract Simple synthetic routes are described to 5,6-dehydroarachidonic acid ( 5 ) cis -8-eicosen-5-ynoic acid 6 ) and the thio analog of (±)-leukotriene A ( 7 ), which are of value in the study of inhibition of the biosynthesis of leukotrienes and slow reacting substances.

Chemical conversion of arachidonic acid to slow reacting substances

Abstract The synthesis of slow reacting substances, leukotrienes C, D, and E, can be accomplished conveniently by a stereoselective biomimetic route. Details are provided for the conversion of 5-HPETE methyl ester 4 to leukotriene methyl ester (2) and thence to leukotrienes C and D.

Proton magnetic resonance spectra of leukotriene a methyl ester (I), leukotriene B methyl ester diacetate (II) and 12-epi-6-E,8-Z-leukotriene B methyl ester diacetate (III; 5-S,12-di-HETE)

Abstract High resolution proton magnetic resonance (pmr) spectra of derivatives of three important 5-oxygenated eicosanoids of synthetic origin, leukotriene A methyl ester (I), leukotriene b methyl ester diacetate (II) and 5- S ,12- S -di-HETE methyl ester diacetate (III) have been obtained. In the case of II and III, good spectra could also be obtained for samples of biological origin although only microgram amounts were available, and their identity with those from synthetic material provided independent confirmation of stereochemistry and structure for leukotriene B and 5- S ,12- S -di-HETE. The complex pmr spectra of I, II and III were also analyzed systematically to determine peak assignments and coupling constants, and from these, significant information with regard to molecular conformation was derived.

Pathways for migration and cleavage of the S-peptide unit of the leukotrienes

Abstract Sulfoxides of leukotriene C ( 2 ) and various analogs ( 5 , 8 ) undergo a 1,7-migration of sulfur (forming diastereomers 3 , 6 , and 9 , respectively) with noteworthy facility. Generation of the S-halo derivatives of leukotriene C in water results in heterolysis of the CS bond to give (5S, 12R)- and (5S, 12S)-6- trans -leukotriene B in a process which mimics biochemical deactivation.