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Faculty

William J. Chain, PhD

William J. Chain, PhD
  • Assistant Professor
    Natural Products and Experimental Therapeutics Program
    University of Hawaii Cancer Center
  • Assistant Professor
    Chemistry, College of Natural Sciences, University of Hawaii at Manoa

Degrees

  • PhD, Chemistry
    Harvard University
  • Postdoctoral
    Princeton University

Research Focus

The Chain group is focused on exploring classical and fundamental reactivity as a means of approaching new and long standing synthetic challenges. Specific interests include the synthesis of several natural products with potent and selective anti-cancer activity, utilizing carbonyl-enabled carbon-carbon bond formations to construct their core structures in short order, and actively developing new methods for the synthesis of medium-sized rings.

Targets under Investigation in the Chain Group



Englerin A

The group has recently achieved an efficient synthesis of englerin A, a guaiane sesquiterpene that was isolated from the bark of Phyllanthus engleri, a plant indigenous to east Africa. The englerins consist of a 5-6-5 fused tricyclic structure with an ether bridge and two ester bearing stereogenic centers, including a highly unusual glycolate residue. Englerin A is a potent and selective inhibitor of the growth of six human renal cancer cell lines, and appears to operate by a new and unknown mechanism of action. The englerins have been the subject of intense study in the synthetic organic chemistry community and several elegant solutions have been described. Their eight-step synthesis of englerin A leverages simple carbonyl-enabled reactions.



This route is the shortest, most efficient preparation of the englerins reported to date, and it is amenable to the production of a diverse series of analogs for structure-function studies and determining the mode of action of these natural products. These studies are currently underway as part of a collaboration with cancer biologists at the University of Hawaii Cancer Center.

Selected Publications

  • Li, Z.; Nakashige, M.; Chain, W. J. A Brief Synthesis of (–)-Englerin A. J. Am. Chem. Soc. 2011, 133, 6553–6556. DOI: 10.1021/ja201921j.
  • Dubinina, G. G.; Chain, W. J. Reactions of azepinones with electrophiles. Tetrahedron Lett., 2011, 52, 939-942. DOI: 10.1016/j.tetlet.2010.12.091
  • Dubinina, G. G.; Yoshida, W. Y.; Chain, W. J. On the preparation of azepinones Tetrahedron Lett. 2010, 51, 5325-5327. DOI: 10.1016/j.tetlet.2010.08.003.

Publication list via PubMed