Synthesis of 12-oxophytodienoic acid (12-oxoPDA) and the compounds of its enzymic degradation cascade in plants, OPC-8:0, -6:0, -4:0 and -2:0 (epi-jasmonic acid), as their methyl esters

Abstract

The synthesis of 12-Oxophytodienoic acid, and the compounds of its enzymic degradation sequence, OPC-8:0, -6:0, -4:0 and -2:0, important plant metabolites derived from linolenic acid, is reported. The syntheses use the known cyclopent-3-ene-1,2-diacetic acid as an early intermediate, and this is derived from the Cope rearrangement of 5-vinyltrinorborn-2-ene via bicyclo[4.3.0]nona-3,7-diene. lodolactonisation and tributyltin hydride reduction provides the key intermediate (3-oxo-2-oxabicyclo[3.3.0]octan-6-yl)acetic acid for the OPC series, whilst phenylselenolactonisation and elimination provides the necessary unsaturated lactone (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid for 12-oxoPDA. Members of the OPC-series were made by chain extending the saturated oxabicyclooctane acid: that for the OPC-4:0 involved double Arndt–Eistert reaction, whilst the intermediates for OPC-6:0 and -8:0 were made by Kolbe anodic crossed coupling. The lactones were then converted via their lactols, Wittig reaction, esterification and oxidation, into the compounds of the OPC ester series, including OPC-2:0 (methyl epi-jasmonate).

The unsaturated lactone 8-(7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)octanoic acid required for 12-oxoPDA synthesis could also be prepared by anodic synthesis either from (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid, or from its 2-phenylseleno-2, 3-dihydro precursor as elimination occurred concomitantly during the reaction. Since yields were low, the unsaturated acid lactone was converted into its lactol and the (Z)-pent-2-enyl side-chain was inserted first. After TBDMS blocking of the cyclopentene hydroxy group, the side-chain was elaborated to give 5-(pent-2-enyl)cyclopent-2-enylacetaldehyde and chain extension carried out by a Grignard-demesylation procedure. Sequential desilylation and depyranylation, followed by oxidation of the diol, gave 12-oxoPDA, isolated as its methyl ester.