acetylenic natural products

Acetylenic compounds have been isolated from a wide variety of plant species, cultures of higher fungi, and marine sponges.  Naturally occurring acetylenes are of particular interest as many of them display important biological activities, namely antibacterial, antimicrobial, antifungal, pesticidal, phototoxic, and medicinal properties.  The ene-triyne 1, was isolated by Bohlmann et al. from Chrysanthemum plant species, e.g. Chrysanthemum leucanthemum L. (common name: oxeye daisy).  Biological studies conducted with compound 1 revealed it to be highly phototoxic to mosquito larvae, namely Aedes atropalpus larvae and Aedes aegypti larvae, with an LC50 of 0.100 ppm and 0.079 ppm, respectively.  Compound 1 was also phototoxic to blackfly larvae (Simulium vittatum) and adult nematodes (Caenorhabditis elegans).  1-Phenylhepta-1,3,5-triyne (2) has been isolated from diverse plant species, e.g. Bidens pilosa L. (Asteraceae) and Coreopsis lanceolata L.  Compound 2 has been extensively studied and was found to display insecticidal activity (LC50 204 ng/cm2) toward larvae of the fall armyworm, as well as antimicrobial activity, ovicidal activity against Drosophila melagonaster, and nematicidal activity.  The high potency of these acetylenes as natural mosquito larvicidal agents make them all the more relevant due to the current threat posed by mosquito-transmitted West Nile virus. 

Some of these compounds have previously been synthesized using conventional methods (with low or no reported yields), while others remain unrealized.  We have now achieved optimized syntheses for many naturally occurring acetylenes using a methodology recently developed in our research group, namely a modification of the Fritsch-Buttenberg-Wiechell rearrangement.[1-4]  The precursors for this reaction are easily prepared from the commercially available carboxylic acids.  This methodology is a versatile way of making polyynes and is being successfully applied to the synthesis of naturally occurring acetylene, such as 1–4.[5]

[1]  "Migrating Alkynes in Vinylidene Carbenoids: An Unprecedented Route to Polyynes," S. Eisler, R. R. Tykwinski. J. Am. Chem. Soc. 2000, 122, 10736-10737.

[2]  "Modification of the Fritsch-Buttenberg-Wiechell Rearrangement: A Facile Route to Unsymmetrical Butadiynes," E. T. Chernick, S. Eisler, R. R. Tykwinski. Tetrahedron Lett. 2001, 42, 8575-8578.

[3]  "Synthesis of Unsymmetrically Substituted 1,3-Butadiynes and 1,3,5-Hexatriynes via Alkylidene Carbenoid Rearrangements," A. L. K. Shi Shun, E. T. Chernick, S. Eisler. R. R. Tykwinski. J. Org. Chem, 2003, 68, 1339-1347.

[4]  "Alkyne Migration in Vinylidene Carbenoid Species: A New Method of Polyyne Synthesis," S. Eisler, N. Chahal, R. McDonald, R. R. Tykwinski. Chem. Eur. J. 2003, 9, 2542-2550.

[5]  "Synthesis of Naturally Occurring Acetylenes via an Alkylidene Carbenoid Rearrangement,” A.L.K. Shi Shun, R.R. Tykwinski, J. Org. Chem. 2003, 68, 1339-1347.

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