Feldman Ken S
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
Phytochemistry. 2005 Sep;66(17):1984-2000. doi: 10.1016/j.phytochem.2004.11.015. Epub 2004 Dec 24.
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 (TNFalpha) 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.
对鞣花单宁植物代谢产物全合成的持续研究已导致制备出二聚体抗肿瘤化合物科里亚林A以及设计的结构类似物。在相关研究中，已实现了带有2,4 - 六羟基二苯甲酰基（HHDP）的吡喃葡萄糖结构的合成。该物质与鞣花单宁的老鹳草素家族有关，其后续化学性质为以下观察结果提供了一个机理依据：在含(3,6 - 桥连)2,4 - HHDP的鞣花单宁中，HHDP单元在体内总是会进一步氧化。旨在测定科里亚林A及其类似物免疫调节特性的配套研究得出这样的结论：肿瘤坏死因子α（TNFα）是这种鞣花单宁肿瘤缓解活性的介质。此外，某些单宁和单宁类似物似乎对外周血单核细胞具有免疫抑制作用，这些外周血单核细胞暴露于细菌衍生的诱导败血性休克的介质脂多糖。
