876723-86-3Relevant articles and documents
Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties
Nelson, Andrew T.,Camelio, Andrew M.,Claussen, Karin R.,Cho, Jiyoon,Tremmel, Lisa,Digiovanni, John,Siegel, Dionicio
, p. 4342 - 4346 (2015/11/03)
The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized on the gram scale. Divergent diastereoselective reductions of α-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti-inflammatory activities as well as cancer chemopreventive activity.
Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies
Wen, Xiaoan,Sun, Hongbin,Liu, Jun,Cheng, Keguang,Zhang, Pu,Zhang, Liying,Hao, Jia,Zhang, Luyong,Ni, Peizhou,Zographos, Spyros E.,Leonidas, Demettes D.,Alexacou, Kyra-Melinda,Gimisis, Thanasis,Hayes, Joseph M.,Oikonomakos, Nikos G.
experimental part, p. 3540 - 3554 (2009/04/07)
Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity (7, 18-20) or no activity (21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb-asiatic acid and GPb-maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition.
Pentacyclic triterpenes. Part 2: Synthesis and biological evaluation of maslinic acid derivatives as glycogen phosphorylase inhibitors
Wen, Xiaoan,Zhang, Pu,Liu, Jun,Zhang, Luyong,Wu, Xiaoming,Ni, Peizhou,Sun, Hongbin
, p. 722 - 726 (2007/10/03)
The synthesis of a series of maslinic acid derivatives is described and their effect on rabbit muscle glycogen phosphorylase a evaluated. Within this series of compounds, 15 (IC50 = 7 μM) is the most potent GPa inhibitor. SAR of the maslinic acid derivatives are discussed.
