Abstract
We recently isolated (11E)-13-hydroxy-10-oxooctadec-11-enoic acid (1) and its fourteen-membered lactone 2 as cytotoxic constitutents of the extract of corn, but we could not determined their absolute configuration of the asymmetric carbon at C-13. Therefore, for purposes of elucidation of the absolute configuration of natural 1 and 2 and comparison between their cytotoxic behavior, we attempted syntheses of both their R- and S-enantiomers from linoleic acid via lipoxygenase- and cobalt porphyrin-catalyzed oxygenation as key step-reactions. Linoleic acid (3) was converted into (13S, 9Z, 11E)-13-hydroperoxyoctadeca-9,11-dienoic acid (4) by soybean lipoxygenase-catalyzed oxygenation, which was treated with NaBH_4 and then diazomethane to give 13S-hydroxy ester 5. Dienoic esters 6a-c were obtained from 5 by protection of the hydroxy group and allowed to react with oxygen and triethylsilane in the presence of a catalytic amount of cobalt porphyrin followed by acetylation of intermediary hydroperoxides, to afford 10-oxo compounds 7a-c and 12-oxo ones 8a-c: The yield of 7 increased with bulkiness of the protection group of 6. Hydrolysis of 7c by use of lipase and then deprotection gave 13S-keto acid S-1. On the other hand, 13R-keto acid R-1 was synthesized by lipase-catalyzed hydrolysis of the corresponding lactone R-2. (13S, 9Z, 11E)-13-hydroxyoctadeca-9,11-dienoic acid (10), obtained from 3 by lipoxygenase-catalyzed oxygenation and reduction with NaBH_4, was cyclized by the Yamaguchi method and by the Mitsunobu method, to give 14-membered lactones S-11 and R-11, respectively. The cobalt porphyrin-catalyzed oxygenation of S-11 and R-11 produced the corresponding 10-oxo lactones S-2 and R-2. Thus, we synthesized successfully the both enantiomers of 1 and 2 from linoleic acid in short steps and now evaluate their cytotoxic activity in progress.
