Premium
Synthesis of 3‐oxalinolenic acid and β‐oxidation‐resistant 3‐oxa‐oxylipins
Author(s) -
Hamberg Mats,
Chechetkin Ivan R.,
Grechkin Alexander N.,
León Inés Ponce,
Castresana Carmen,
Bannenberg Gerard
Publication year - 2006
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-006-5123-5
Subject(s) - chemistry , stereochemistry , oxylipin , lipoxygenase , acetic acid , aldehyde , allene , yield (engineering) , organic chemistry , enzyme , catalysis , materials science , metallurgy
3‐Oxalinolenic acid (3‐oxa‐9(Z), 12(Z), 15(Z)‐octadecatrienoic acid or (6(Z), 9(Z), 12(Z)‐pentadecatrienyloxy)acetic acid) was synthesized from 5(Z), 8(Z), 11(Z), 14(Z), 17(Z)‐eicosapentaenoic acid by a sequence involving the C15 aldehyde 3(Z), 6(Z), 9(Z), 12(Z)‐pentadecatetraenal as a key intermediate. Conversion of the aldehyde by isomerization and two steps of reduction afforded 6(Z), 9(Z), 12(Z)‐pentadecatrienol, which was coupled to bromoacetate to afford after purification by HPLC >99%‐pure 3‐oxalinolenic acid in 10–15% overall yield. 3‐Oxalinolenic acid was efficiently oxygenated by soybean lipoxygenase‐1 into 3‐oxa‐13(S)‐hydroperoxy‐9(Z), 11(E), 15(Z)‐octadecatrienoic acid, and this hydroperoxide could be further converted chemically into 3‐oxa‐13(S)‐hydroxy‐9(Z), 11(E), 15(Z)‐octadecatrienoic acid and 3‐oxa‐13‐oxo‐9(Z), 11(E), 15(Z)‐octadecatrienoic acid. The 3‐oxa‐hydroperoxide also served as the substrate for the plant enzymes allene oxide synthase, divinyl ether synthase, and hydroperoxide lyase to produce 3‐oxa‐12‐oxo‐10, 15(Z)‐phytodienoic acid and other 3‐oxa‐oxylipins that were characterized by MS, 3‐Oxalinolenic acid was not oxygenated by 9‐lipoxygenase from tomato but was converted at a slow rate into 3‐oxa‐9(S)‐hydroperoxy‐10(E), 12(Z), 15(Z)‐octadecatrienoic acid by recombinant maize 9‐lipoxygenase. Recombinant α‐dioxygenase‐1 from Arabidopsis thaliana catalyzed the conversion of 3‐oxalinolenic acid into a 2‐hydroperoxide, which underwent spontaneous degradation into a mixture of 6,9,12‐pentadecatrienol and 6,9,12‐pentadecatrienyl formate. A novel α‐dioxygenase from the moss Physcomitrella patens was cloned and expressed and was found to display the same activity with 3‐oxalinolenic acid as Arabidopsis thaliana α‐dioxygenase‐1. Lipoxygenase‐generated 3‐oxa‐oxylipins are resistant toward β‐oxidation and have the potential for displaying enhanced biological activity in situations where activity is limited by metabolic degradation.