One-pot synthesis of bioactive cyclopentenones from α-linolenic acid and docosahexaenoic acid. Issue 7 (1st April 2018)

• Record Type: Journal Article
• Authors: Maynard, Daniel; Müller, Sara Mareike; Hahmeier, Monika; Löwe, Jana; Feussner, Ivo; Gröger, Harald; Viehhauser, Andrea; Dietz, Karl-Josef
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 7(2018)
• Page Start: 1356
• Page End: 1364
• Publication Date: 2018-04-01
• Subjects: ARA arachidonic acid -- AOC allene oxide cyclase -- AOS allene oxide synthase -- Cyp20-3 cyclophilin 20-3 -- DHA docosahexaenoic acid -- EDH 16, 17-epoxy-4, 7, 10, 13, 15, 19-docosahexaenoic acid -- EOT 12, 13-epoxy-9, 11, 15-octadecatrienoic acid -- LeA linolenic acid -- HPDH 17-hydroperoxy-4, 7, 13, 15, 19-docosahexaenoic acid -- LOX lipoxygenase -- LOX6 LOX6 of Arabidopsis thaliana -- OCPD ((4Z, 7Z, 10Z)-12-[[-(1S, 5S)-4-oxo-5-(2Z)-pent-2-en-1yl] cyclopent-2-en-1yl] dodeca-4, 7, 10-trienoic acid) -- 12-OPDA cis-(+)-12-oxo-phytodienoic acid -- PUFAs poly unsaturated fatty acids -- RP-HPLC reverse phase high-performance liquid chromatography -- SLOX soybean lipoxygenase; One-pot synthesis -- 12-OPDA -- Cyclophilin 20-3 -- Docosahexaenoic acid -- Lipoxygenase -- Protein-ligand interaction -- Bioactivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.061
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Oxidation products of the poly-unsaturated fatty acids (PUFAs) arachidonic acid, α-linolenic acid and docosahexaenoic acid are bioactive in plants and animals as shown for the cyclopentenones prostaglandin 15d-PGJ2 and PGA2, cis -(+)-12-oxophytodienoic acid (12-OPDA), and 14-A-4 neuroprostane. In this study an inexpensive and simple enzymatic multi-step one-pot synthesis is presented for 12-OPDA, which is derived from α-linolenic acid, and the analogous docosahexaenoic acid (DHA)-derived cyclopentenone [(4 Z, 7 Z, 10 Z )-12-[[-(1 S, 5 S )-4-oxo-5-(2 Z )-pent-2-en-1yl]-cyclopent-2-en-1yl] dodeca-4, 7, 10-trienoic acid, OCPD]. The three enzymes utilized in this multi-step cascade were crude soybean lipoxygenase or a recombinant lipoxygenase, allene oxide synthase and allene oxide cyclase from Arabidopsis thaliana . The DHA-derived 12-OPDA analog OCPD is predicted to have medicinal potential and signaling properties in planta . With OCPD in hand, it is shown that this compound interacts with chloroplast cyclophilin 20-3 and can be metabolized by 12-oxophytodienoic acid reductase (OPR3) which is an enzyme relevant for substrate bioactivity modulation in planta .