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United States Department of Agriculture

Agricultural Research Service

Research Project: Chemical Biology of Insect and Plant Signaling Systems

Location: Chemistry Research Unit

Title: Synthesis of the Caeliferins, elicitors of plant immune responses: accessing Lipophilic natural products via cross metathesis

Authors
item O'Doherty, Insih -
item Yim, Joshua -
item Schmelz, Eric
item Schroeder, Frank -

Submitted to: Organic Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 1, 2011
Publication Date: October 12, 2011
Citation: O'Doherty, I., Yim, J.J., Schmelz, E.A., Schroeder, F.C. 2011. Synthesis of the Caeliferins, elicitors of plant immune responses: accessing Lipophilic natural products via cross metathesis. Organic Letters. 13(21):5900-5903.

Interpretive Summary: In response to insect attack plants exhibit dynamic induced responses that include increases in biochemical defenses that inhibit insect growth. In some cases, specific insect-derived elicitors have been demonstrated to mediate this plant defense activation. Despite these advances, further progress is constrained by the difficultly of synthesizing the unique and often labile natural products. Working with the Boyce Thompson Institute (Ithaca, New York) scientists at the Center for Medical, Agricultural and Veterinary Entomology in Gainesville, FL, have discovered a useful strategy in the enantioselective synthesis of a series of grasshopper-derived elicitors. These disulfo-oxy fatty acids, termed caeliferins, are present at very high concentrations in grasshopper oral secretions and elicit defense responses in multiple plant species. Using a combination of cross metathesis, selective catalysts, and hydride scavengers the approach successfully coupled long-chain aliphatic substrates to yield the desired synthetic elicitors. This work enables the synthesis of sufficient quantities of insect-derived elicitors for detailed mode-of-action studies that address how plants perceive insect attack.

Technical Abstract: We report a cross metathesis- (CM-) based syn-thesis of the caeliferins, a family of sulfooxy fatty acids that elicit plant immune responses. Unexpectedly, detailed NMR-spectroscopic and mass spectrometric analyses of CM reaction mixtures revealed extensive isomerization and homologation of starting materials and products. Isomerization and homologation could be suppressed by using Grubbs 1st generation (G-I) catalyst with 1,4-benzoquinone as a hydride scavenger, whereas more active CM catalysts inevitably produced significant amounts of isomerized and homologated side-products. We show that the degree of isomerization and homologation in CM strongly correlates with alkene chain lengths and thus long-chain aliphatic substrates are particularly susceptible. Our study highlights specific challenges in the use of CM for lipophilic substrates in natural products synthesis or ADMET.

Last Modified: 7/31/2014