Download PDF
Synlett 2008(9): 1353-1356  
DOI: 10.1055/s-2008-1072750
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Cycloaddition Strategy for Use toward Berkelic Acid, an MMP Inhibitor and Potent Anticancer Agent Displaying a Unique Chroman Spiroketal Motif

Yaodong Huang, Thomas R. R. Pettus*
Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara CA 93106-9510, USA
Fax: +1(805)8935690; e-Mail: pettus@chem.ucsb.edu;
Further Information

Publication History

Received 8 February 2008
Publication Date:
07 May 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

A kinetically controlled diastereoselective cycloaddition between a chiral enol ether and an ortho-quinone methide (o-QM) produces a chroman spiroketal motif that is found in the core of berkelic acid, a novel matrix metalloproteinase (MMP) inhibitor and potent anticancer agent. The transformation lays the groundwork for preparation of future inhibitors aimed at distinguishing among the active sites of the twenty-three known MMP. Experimental findings suggest that the stereochemistry that emerges from cycloaddition is opposite that which results from thermodynamic ketalization.

Key words

o-quinone methide - chroman spiroketal - berkelic acid - diastereoselective synthesis - MMP - anticancer agent - ketalization