Recent progress in ellagitannin chemistry

The synthesis of the tumoricidal dimeric ellagitannin, coriariin A, is described, along with related studies on the synthesis of a C(2)/C(4)-HHDP-containing model related to a putative geraniin biosynthesis precursor. The results of immunomodulatory assays with tannins and designed analogues attest to the promise that these species have in the distinct areas of tumor remission and anti-sepsis therapy. Continuing studies on the total synthesis of ellagitannin plant metabolites have led to the preparation of the dimeric antitumor compound, coriariin A, as well as designed structural analogues. In related investigations, the synthesis of a 2,4-hexahydroxydiphenoyl (HHDP)-bearing glucopyranose structure has been achieved. This species is related to the geraniin family of ellagitannins, and its subsequent chemistry is suggestive of a mechanistic rationale for the observation that the HHDP units within (3,6-bridged)2,4-HHDP-containing ellagitannins invariably are oxidized further in vivo. Companion studies designed to assay the immunomodulatory properties of coriariin A and analogues have led to the thesis that tumor necrosis factor alpha (TNFα) serves as a mediator of this ellagitannin’s tumor remissive activity. Furthermore, certain tannins and tannin analogues appear to act in an immunosuppressive capacity with peripheral blood monocytes that were exposed to the bacterially derived septic shock inducing agent lipid A.