Oxidation of oxa and thia fatty acids and related compounds catalysed by 5-and 15-lipoxygenase

The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14 -tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic a cid, 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(e icosa-5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14-t etraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic ac id, all react with soybean 15-lipoxygenase. The products were treated with triphenylphosphine to give alcohols, which were isolated using HPLC. Analys is of the alcohols using negative ion tandem electrospray mass spectrometry , and by comparison with compounds obtained by autoxidation of arachidonic acid, shows that each enzyme catalysed oxidation occurs at the omega -6 pos ition of the substrate. In a similar fashion, it has been found that (Z,Z,Z )-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trieny loxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid and N -[(all-Z)-(eicosa-5,8, 11.14-tetraenylthio)]propionic acid each undergoes r egioselective oxidation at the carboxyl end of the polyene moiety on treatm ent with potato 5-lipoxygenase. Neither (all-Z)-(eicosa-5,8,11,14-tetraenyl thio)succinic acid nor N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic ac id reacts in the presence of this enzyme, while N-[(all-Z)-(eicosa-5,8,11,1 4-tetraenoyl)]glycine affords the C11' oxidation product. The alcohol deriv ed from (Z,Z,Z)-(octadeca-6,9, 12-trienyloxy)acetic acid using the 15-lipox ygenase reacts at the C6' position with the 5-lipoxygenase. (C) 2001 Elsevi er Science Ltd. All rights reserved.