Friday, January 23, 2009
α-Cyclopiazonic Acid: A Biomimetic Synthetic Study
MARC U*STAR Fellow
Title: ?-Cyclopiazonic Acid: A Biomimetic Synthetic Study By: James A. Nunnelley (B.S., Chemistry, 2008, Cal State University Los Angeles) Process R&D Â Chemistry Mentor: Collin Chan In 1968, an interesting mycotoxin was isolated and characterized by Dr. Holzapfel that was found to be the principle toxin of the fugal species Penicillium cyclopium Westling.1 Although this fungal species was detrimental to grain stocks, it was discovered that the mycotoxin that it produced (?-Cyclopiazonic Acid ) was useful in studies of the (SR) Ca+2 pump, in coronary artery cells of pigs.2 Aside from its biological applications, ?-Cyclopiazonic Acid (?-CPA) is interesting from the synthetic point of view. Dr. Holzapfel and Dr. Vleggaar, et al. demonstrated that the bio-synthesis of ?-CPA involves tryptophan, ?-CPA, and intermediate I.3 ?-CPA I II A biomimetic synthetic study, therefore, should involve intermediates that are analogs of ?-CPA and I. In the present biomimetic study, intermediate II was successfully synthesized, characterized by NMR spectroscopy and X-ray diffraction crystallography. Efforts were, also, made to substitute an allylic prenyl group at the 4 position of the indole moiety. Progress toward the synthesis of the target molecule ?-CPA is reported here. (1) Holzapfel, C. W. Tetrahedron, 1968, 24(5), 2101. (2) Grover, A. K. Am. J. Physiol Cell Physiol, 1996, 271(1), C181. (3) Vleggaar, R. J. Chem. Soc., Perkin Trans. 1, 1981, 3292.