| The syntheses of three fluorescent tannin analogues (two monomers and one dimer) was accomplished. The synthesis of the dimeric ellagitannin/gallotannin proved especially challenging. The onset of the synthesis involved a hetero Diels-Alder dimerization of an orthoquinone unit catalyzed by Sc(OTf) 3 to produce the core of the molecule, and a [3+2]-cycloaddition using a modification to the Sharpless Cu(I)-catalyzed protocol to attach the fluorescent tags. Several in vivo biological experiments were performed with these synthetic tannins and disappointedly the dimeric tannin was found inactive (unable to elicit TNF-alpha secretion from J744 cells). However, the two monomeric fluorescent gallotannins were found as active as the parent penta- O-galloyl-beta-D-glucose that will allow further probing into the exact biological mechanism by which these tannins are able to achieve their documented tumoricidal action.;Furthermore, studies towards the synthesis of lihouidine, a marine natural product with moderate anticancer properties, were pursued. A Buchwald-Hartwig arylamination was used to join two early fragments. Numerous acidic aerobic conditions failed to cyclize this adduct through a proposed biomimetic electrocyclization. Gratifyingly, subjection of this adduct to fuming nitric acid led to an unprecedented nitration/Michael-like cyclization cascade to form a key advanced intermediate in the synthesis. |
