Total Synthesis of Depsilairdin

Abstract

The total synthesis of depsilairdin, a host-selective phytotoxin isolated from Leptosphaeria maculans (the causal agent of blackleg disease of oilseed Brassicas), has been achieved by N-terminal extension of a suitably protected derivative of the hitherto unknown amino acid (2S,3S,4R)-3,4-dihydroxy-3-methyl-proline (Dhmp) followed by esterification with lairdinol A. The latter esterification, complicated by the sterically hindered nature of the carboxyl group, was accomplished by a novel method involving reaction of the 1-hydroxybenzotriazole (HOBt) derived active ester with the bromomagnesium alkoxide of lairdinol A. Three depsilairdin analogues were also prepared by replacing the Dhmp residue with L-proline and cis-and trans-4-hydroxy-L-proline. Phytotoxicity assays showed that the analogues were nontoxic to both blackleg-susceptible (brown mustard) and -resistant (canola) plants, suggesting that the presence of the Dhmp residue in depsilairdin is important for its host-selective toxicity toward brown mustard.

Phytotoxic secondary metabolites and peptides produced by plant pathogenicDothideomycetefungi

“…The structure of phomalide has been recently resolved as a rare cyclic depsipeptide with three a-amino acids and two a-hydroxy acids ( Fig. Analysis of phytotoxicities showed that the three analogs were no longer toxic to both brown mustard and canola, suggesting that the presence of Dhmp in the chemical structure of depsilairdin is required for its biological activity and host-selectivity to brown mustard (Ward & Pardeshi, 2010). Interestingly, the structural analog isophomalide that contains (Z)-dehydrobutyrine shows no phytotoxic activity against Brassica species, while the saturated dihydrophomalide causes chlorotic symptoms on the resistant brown mustard but not on canola, indicating that both the presence and configuration of the (E)-double bond is crucial for selective phytotoxicity (Siodlak et al, 2011).…”

“…Recently, the complete synthesis of depsilairdin and three depsilairdin analogs, in which the Dhmp residue was replaced with L-proline and cis-and trans-4-hydroxy-L-proline has been achieved. Analysis of phytotoxicities showed that the three analogs were no longer toxic to both brown mustard and canola, suggesting that the presence of Dhmp in the chemical structure of depsilairdin is required for its biological activity and host-selectivity to brown mustard (Ward & Pardeshi, 2010). A new set of selective phytotoxins, named maculansins A and B have also been recently isolated from virulent isolates of L. maculans (Pedras & Chumala, 2011).…”

Natural sesquiterpenoids

“…265 Enantioselective total syntheses of dihydrojuneol 266 and (+)-carainterol A 267 have been accomplished, while depsilairdin has been synthesized by esterification of lairdinol A with a tetradepsipeptide. 268 A preparation of ar-occidol has been reported. 269 The sesquiterpene 1a-hydroxy-b-dihydroagarofuran has been obtained from the fruits of Cryptomeria fortunei.…”