Stereocontrolled Synthesis of a Complex Library via Elaboration
of Angular Epoxyquinol Scaffolds
Xiaoguang Lei,Nava Zaarur,Michael Y. Sherman, andJohn A. Porco, Jr.*
Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU),
Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, and Department of
Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118
porco@chem.bu.edu
Received May 12, 2005
Abstract:
We have accomplished the synthesis of a complex chemical library via elaboration of angular
epoxyquinol scaffolds with distinct skeletal frameworks. The key strategy involves highly stereocontrolled [4 + 2] Diels-Alder cycloadditions of chiral, nonracemic epoxyquinol dienes to generate
the scaffolds. Further scaffold diversification involves hydrogenation, epimerization, dehydration,
and condensation of the carbonyl group with alkoxyamine and carbazate building blocks. Further
elaboration of the scaffolds also provided new skeletal frameworks using hydroxyl-directed Diels-Alder cycloaddition and reductive N-N bond cleavage. The overall process afforded 244 highly
complex and functionalized compounds. Preliminary biological screening of the library uncovered
six compounds which showed significant inhibition of Hsp 72 induction.
