Total Synthesis of Jerangolid D

Jiri Pospisil and Istvan E. MarkoCatholic University of Louvain, Belgium

JACS ASAP

Nilu Jayasuriya @ Wipf Group 1 3/18/2007

Jerangolid• Isolated from

myxobacteriumSorangium cellulosum

• Anti-fungal agentsactivity againstHansenula anolmala andMucor hiemalis (70ng/mL); Pichiamembranaefaciens,Debaryomyces hansenii,Trichosoron terrestre(0.1-0.4 µg/mL), andTrichoderma hamata,Botritis cinerea, andCandida albicans (4-7 µg/mL)

• Mechanism of actionunknown

Gerth, K.; Washausen, P.; Hofle, G.; Irschik, H.; Reichenbach, H. J. Antibiot. 1996, 49, 71-75.

Nilu Jayasuriya @ Wipf Group 2 3/18/2007

Myxobacteria• Unicellular rod-shaped bacteria• Found in soil• Move by gliding• Synthesize a large number of

biologically active secondarymetabolites

Dawid, W.; FEMS Microbiology Rev. 2000, 24, 403-427.

Nilu Jayasuriya @ Wipf Group 3 3/18/2007

Ambruticin/Jerangolid

• Activity of Ambruticin andJerangolid are similar

• Mode of action- affects theosmoregulation system ofsusceptible fungi

• Increase the amount of glyceroland accumulation of fatty acids,cells starts leaking results in celldeath.

Genet, J-P.; Michelet, V. Curr. Org. Chem. 2005, 9, 405-418.

Nilu Jayasuriya @ Wipf Group 4 3/18/2007

Previous synthesis of Abruticin-eastern fragment

Kende, 1990: Hetero-Diels Alder/Ireland-ClaisenJacobsen 2001:

Martin, 2001:

Kende et al. J. Am. Chem. Soc. 1990, 112, 9645.;Jacobsen, E.; Liu, P. J. Am. Chem. Soc. 2001, 123, 10772;Martin, S et al. Tetrahedron 2003, 59, 6819.; Lee et al. Angew. Chem. Int. Ed. 2002, 41, 176.

Lee, 2002: Auxiliary/Metathesis

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Silyl modified Sakurai

Marko, I.; Mekhalfia, A. Tetrahedron Lett. 1991, 32(36), 4779-4782.Marko, I.; Mekhalfia, A.; Adams, H. Tetrahedron Lett. 1991, 32(36), 4779-4782.

-1990

-1991: Intramolecular

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Sakurai AMCR

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Summary

• First total synthesis of Jerangolid in 22 steps in 6.1% overall yield.

• Utilized the silyl modified sakurai reaction

• Synthesis of analogues and other members of the Jerangolid family

Nilu Jayasuriya @ Wipf Group 14 3/18/2007