Syntheses of the ethyl esters of the plant host-selective (H-S) toxins (AF-IIa, AF-IIc and AK-II) produced by pathotypes of Alternaria alternata
Total syntheses of the ethyl esters of the host-selective (H-S) toxins produced by Alternaria alternata(strawberry-type pathogen), AF-IIa and AF-IIc, and by the Japanese pear-type AK-II are reported. The initial synthetic objectives, the 2E,4E,6E, 2E,4Z,6E and 2E,4E,6Z stereoisomers of ethyl 8-hydroxy-9-methyldeca-2,4,6,9-tetraenoate, were attained by the use of acetylene hydrometallation and Pd0-mediated vinyl halide coupling: for this purpose tin chemistry was superior to the use of zirconium compounds. The tetraene-hydroxy esters were epoxidised selectively at the 9,10-double bond by the Sharpless procedure under conditions of kinetic control (50% reaction), which it was predicted would lead to products of predominantly (8R,9S)-stereochemistry. Esterification of the epoxides produced from the 2E,4E,6E and 2E,4E,6Z hydroxy esters with synthetic (2R,3S)-2-(t-butyldimethylsiloxy)-3-methylpentanoic acid, followed by HPLC separation, gave as the major products, stereoisomers which, after deprotection, were characterised as the ethyl esters AF-toxin IIc and AF-toxin IIa. The stereochemical nature of the minor products in the epoxidations is considered. For the synthesis of the AK-II toxin as its ethyl ester, similar esterification with N-acetyl-L-phenylalanine was carried out, except that racemisation of the amino acid centre ensued. This led to two major products which were separated and identified as (8R,9S,2′S)- and (8R,9S,2′R)-stereoisomers, the former being identical with the ester of AK-II toxin.