Enantiospecific syntheses of leukotrienes C4, D4 and E4 and [14,15-3H2]leukotriene E4 dimethyl ester

Article abstract of DOI:10.1021/ja00349a053

A 'chiral-pool' approach was employed to synthesize various leukotrienes (slow-reacting substance of anaphylaxis, SRS-A) enantiospecifically. The pivotal (S,S)-trans-epoxy alcohol 9 was prepared by efficient and facile routes starting from erythorbic acid (D-araboascorbic acid, 13). This epoxide could also be produced starting from D-glucose. The epimeric (S,R)-cis-epoxide 38 was obtained utilizing L-tartaric acid as the chiral starting material. Elaboration of 9 into leukotriene A₄ methyl ester (5) and the potassium salts of leukotrienes C₄ (4a), D₄ (4b), and E₄ (4c) was accomplished by standard methods. These salts exhibited potent contractile activities in the in vitro guinea pig ileum assay. Reduction of 14,15-dehydroleukotriene A₄ methyl ester (44) with tritium gas gave [14,15-³H₂]-5 and subsequently the dimethyl ester of [14,15-³H₂]leukotriene E₄ having a high specific activity of 40 Ci/mmol.