Formation of prostaglandin A analogues via an allene oxide.

摘要: One potential biosynthetic route to the prostaglandins involves participation of lipoxygenase and allene oxide synthase enzymes, giving a hydroxylated oxide, which then might cyclize form prostaglandin A or close analogue. We have tested model this type transformation using 8-hydroxy-15S-hydroperoxy eicosanoids as substrates for dehydrase (allene synthase) in flaxseed. Four these substrates, each with 9E,11Z,13E-conjugated triene, gave an observable rate reaction. The two derived from eicosapentaenoic acid reacted more rapidly than corresponding arachidonic analogues. Also, 8S-hydroxy-15S-hydroperoxy diastereomers their 8R-hydroxy Products were characterized by high pressure liquid chromatography, UV, gas chromatography-mass specrometry, 1H NMR, CD. Reaction (8S)-hydroxy-(15S)-hydroperoxy-eicosapentaenoic alpha-ketols [8S),15-dihydroxy-14-oxoeicosa-5Z,9E,11Z,17Z+ ++-tetraenoic 11E isomer 2:1 ratio), together four A3 analogues differed configurations side chains. Oxygen 18 labeling fully supported intermediacy biosynthesis. "8R" substrate was converted enantiomers products plus three 13-hydroxy-14,15-epoxy derivatives. arachidonate formed epoxy-hydroxy derivatives, alpha-ketols, A2 trans configuration These results demonstrate (i) feasible metabolism hydroxy (ii) resulting analogue, (iii) marked influence hydroxyl reaction profile products. Some reactions may occur natural pathway prostanoid biosynthesis corals other organisms.