- Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties
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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.
- Nelson, Andrew T.,Camelio, Andrew M.,Claussen, Karin R.,Cho, Jiyoon,Tremmel, Lisa,Digiovanni, John,Siegel, Dionicio
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p. 4342 - 4346
(2015/11/03)
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- Biocatalytic Synthesis of the Anti-diabetes Agent-corosolic Acid by Whole Cells of Microorganisms
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Diabetes is one of the most prevalent and costly global diseases. For diabetes, frequent insulin treatment and synthetic drugs are very expensive and may cause unwanted side effects. Corosolic acid (CA), a natural product, was reported to be efficient in the treatment of diabetes, meanwhile without induction of anti-insulin antibodies and obesity. The preparation of CA attracted many researchers in the world. This study investigated the biocatalytic synthesis method of CA from ursolic acid by Streptomyces griseus subsp. griseus 4.18. LC-MS analysis demonstrated that 5 day, 125 μg/mL substrate, pH=9 and 10% strain concentration were the appropriate conditions. It is estimated that biocatalysis will contribute to the development of green and sustainable synthetic processes with less time-consuming and more environmentally friendly.
- Fu, Shaobin,Meng, Qingfeng,Long, Shu-An,Zhang, Yun,Sun, Di-An,Wei, Gang
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p. 871 - 874
(2015/10/29)
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- Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies
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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.
- 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.
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experimental part
p. 3540 - 3554
(2009/04/07)
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- Process for preparing high purity corosolic acid and high purity ursolic acid
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According to the present invention, there is provided a process for preparing corosolic acid comprising the steps of (1) dissolving crude extract of Japanese loquat leaves in alkali and aqueous alcohol and (2) applying the solution to a nonpolar adsorption resin to obtain corosolic acid.
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Page/Page column 5-6
(2008/12/04)
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- Pentacyclic triterpenes. Part 5: Synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases
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The synthesis and biological evaluation of corosolic acid derivatives and related compounds as inhibitors of rabbit muscle glycogen phosphorylase a is described. Within this series of compounds, 8 (IC50 = 7.31 μM), 12d (IC50 = 3.26 μM), and 12e (IC50 = 5.1 μM) exhibited more potent activities than the parent compound 1 (IC50 = 20 μM). SAR of these compounds is also discussed.
- Wen, Xiaoan,Xia, Jun,Cheng, Keguang,Zhang, Liying,Zhang, Pu,Liu, Jun,Zhang, Luyong,Ni, Peizhou,Sun, Hongbin
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p. 5777 - 5782
(2008/04/03)
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- Process for producing corosolic acid
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This invention provides an improved process for producing corosolic acid starts from ursolic acid, which occurs in plants in relatively large amounts, the method comprising the steps of oxidizing the hydroxyl group at 3-position and utilizing the carbonyl group at 3-position to introduce a hydroxyl group stereospecifically into the 3-oxoursolic acid at the 2α-position adjacent to the hydroxyl group at 3-position.
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Page/Page column 7
(2008/06/13)
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- Insulin secretion potentiator
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The invention provides an early insulin secretion stimulator comprising corosolic acid, etc. The early insulin secretion stimulator of the invention is capable of rapidly inducing secretion of insulin immediately after meals without inducing secretion of insulin in the absence of blood glucose increase.
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Page/Page column 5
(2008/06/13)
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- Pentacyclic triterpenes. Part 1: The first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases
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The semi-synthesis, in vitro and in vivo biological evaluation of corosolic acid (1) and maslinic acid (2) are described. Compounds 1 and 2 represent a new class of inhibitors of glycogen phosphorylases. Both 1 and 2 inhibit the increase of fasted plasma glucose of diabetic mice induced by adrenaline. It is therefore proposed that naturally occurring pentacyclic triterpenes 1 and 2 might reduce blood glucose, at least in part, through inhibiting hepatic glycogen degradation.
- Wen, Xiaoan,Sun, Hongbin,Liu, Jun,Wu, Guanzhong,Zhang, Luyong,Wu, Xiaoming,Ni, Peizhou
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p. 4944 - 4948
(2007/10/03)
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- LAGRENYL ACETATE AND LAGERENOL, TWO TETRACYCLIC TRITERPENOIDS WITH THE CYCLOARTANE SKELETON FROM LAGERSTROEMIA LANCASTERI
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Lagerenyl acetate and lagerenol, two new tetracyclic triterpenoids with the cycloartane skeleton, together with four other triterpenoids 2α-hydroxy-3β-E-p-coumaryloxy-urs-12-en-28-oic acid (jacoumaric acid, isolated as its monoacetylmethylcarboxylate derivative), 2α-hydroxyursolic acid (isolated as its diacetate), germanicyl acetate and friedelin, and sitosterol were isolated from the leaves and twigs of Lagerstroemia lancasteri.The structures of lagerenyl acetate and lagerenol were established as 3β-acetoxycycloart-24-one and 3β-hydroxycycloart-24-one, respectively, on the basis of spectral and chemical evidence.Key Word Index - Lagerstroemia lancasteri; Lythraceae; triterpenoids; lagerenyl acetate; lagerenol; 2α-hydroxy-3β-E-p-coumaryloxy-urs-12-en-28-oic acid; 2α-hydroxyursolic acid; germanicyl acetate; friedelin; β-sitosterol.
- Talapatra, Bani,Chaudhuri, Prabir K.,Mallik, Asok K.,Talapatra, Sunil K.
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p. 2559 - 2562
(2007/10/02)
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- TRITERPENOID SAPOGENOLS FROM THE LEAVES OF CAREYA ARBOREA: STRUCTURE OF CAREYAGENOLIDE
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The acid hydrolysate of the ethanol extract of Careya arborea leaves afforded a new triterpenoid lactone designated careyagenolide along with maslinic acid and 2α-hydroxy ursolic acid.The structure of careyagenolide has been established as 2α,3β-dihydroxytaraxastan-28,20β-olide by a variety of spectroscopic evidence, chemical transformations and correlation with ψ-taraxasterol.Key Word Index - Careya arborea; Lecythidaceae; careyagenolide; maslinic acid; 2α-hydroxy ursolic acid.
- Das, Manik C.,Mahato, Shashi B.
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p. 2069 - 2074
(2007/10/02)
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