464876-77-5

Upstream product

• 100-44-7 benzyl chloride 
• 108-30-5 succinic acid anhydride 
• 4373-41-5 maslinic acid 
• 100-39-0 benzyl bromide 
• 303114-51-4 oleanolic acid benzyl ester 
• 508-02-1 Oleanolic acid 
• 869788-74-9 (4aS,6aS,6bR,12aR)-benzyl 2,2,6a,6b,9,9,12a-heptamethyl-10-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylate 
• 876723-81-8 2α-hydroxy-3-oxoolean-12-en-28-oic acid benzyl ester 
• 869788-75-0 (4aS,6aS,6bR,8aR,12aR,12bR,14bS)-10-Acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,12,12a,12b,13,14b-hexadecahydro-2H-picene-4a-carboxylic acid benzyl ester 
• 908094-04-2 phenyldiazomethane 

Downstream Products

• 876724-09-3 2-hydroxyethyl (2α,3β)-2,3-dihydroxy-olean-12-en-28-oate 
• 1575561-28-2 C₄₀H₅₈O₅ 
• 1575561-31-7 C₄₃H₆₂O₆ 
• 1575561-33-9 C₄₁H₆₀O₅ 
• 1575561-37-3 C₄₅H₆₆O₆ 
• 1575561-39-5 C₄₃H₆₄O₅ 
• 1575561-41-9 C₄₉H₇₄O₆ 
• 1575561-44-2 C₄₉H₇₆O₅ 
• 1575561-46-4 C₆₁H₉₈O₆ 
• 1575561-48-6 C₄₄H₅₈O₅ 
• 1575561-53-3 C₅₁H₆₂O₆ 
• 1575561-56-6 C₄₅H₅₈O₇ 
• 1575561-59-9 C₅₃H₆₂O₁₀ 
• 1575561-67-9 C₄₂H₆₀O₇ 

Relevant academic research and scientific papers

Synthesis of water soluble glycosides of pentacyclic dihydroxytriterpene carboxylic acids as inhibitors of α-glucosidase

A series of compounds were synthesized by glycosylation of maslinic acid (MA) and corosolic acid (CA) with monosaccharides and disaccharides, and the structures of the derivatives were elucidated by standard spectroscopic methods including 1H NMR, 13C NMR and HRMS. The α-glucosidase inhibitory activities of all the novel compounds were evaluated in vitro. The solubility and inhibitory activity of α-glucosidase assays showed that the bis-disaccharide glycosides of triterpene acids possessed higher water solubility and α-glucosidase inhibitory activities than the bis-monosaccharide glycosides. Among these compounds, maslinic acid bis-lactoside (8e, IC50 = 684 μM) and corosolic acid bis-lactoside (9e, IC50 = 428 μM) had the best water solubility, and 9e exhibited a better inhibitory activity than acarbose (IC50 = 478 μM). However, most of glycosylated derivatives possessed lower inhibitory activities than the parent compounds, although their water solubility was enhanced obviously. Moreover, the kinetic inhibition studies indicated that 9e was a non-competitive inhibitor, and structure-activity relationships of the derivatives are also discussed.

Semi-synthesis and antiproliferative evaluation of PEGylated pentacyclic triterpenes

Several PEGylated derivatives of oleanolic and maslinic acids have been semi-synthesized, attaching one acid-PEG reagent to the hydroxyl group/s at C-2 or C-2/C-3 of the A rings of these natural triterpenes, and also to their corresponding C-28 benzyl derivatives. Several monomeric and dimeric PEGylated compounds have also been produced by linking one diamine-PEG reagent to the carboxyl group at C-28 of the same natural triterpenes and also to their corresponding C-2 or C-2/C-3 acetylated derivatives. The cytotoxic effects of 12 triterpenic PEGylated derivatives in three cancer-cell lines (B16F10, HT29, and Hep G2) have been assayed. The best results have been achieved by the PEGylated-amine derivative of oleanolic acid, with IC50 concentrations between 0.22 and 3.78 μM, being between 28- and 963-fold more effective than its natural precursor. The percentages of apoptosis induction have also been determined for the five PEGylated derivatives with the lowest cytotoxicity data. All five compounds showed apoptotic effects on the treated cells, with a total apoptosis rate of 99% in the B16F10 cells, 80% in the Hep G2 cells, and 51% in the HT29 cells. We have also studied the changes in the mitochondrial membrane potential (MMP) to elucidate the possible mechanism involved in the apoptotic responses (intrinsic or extrinsic). Finally, to verify the results found in the cytometry assays, we have used fluorescence microscopy techniques to determine changes in the cell morphology. These PEGylated derivatives of natural triterpenoids, which can induce apoptosis at very low concentrations in different tumour lines, may represent new effective therapeutic drugs against these diseases.

Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties

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.

Converting maslinic acid into an effective inhibitor of acylcholinesterases

During the last decade, maslinic acid has been evaluated for many biological properties, e.g. as an anti-tumor or an anti-viral agent but also as a nutraceutical. The potential of maslinic acid and related derivatives to act as inhibitors of acetyl- or butyryl-cholinesterase was examined in this communication in more detail. Cholinesterases do still represent an interesting group of target enzymes with respect to the investigation and treatment of the Alzheimer's disease and other dementia illnesses as well. Although other triterpenoic acids have successfully been tested for their ability to act as inhibitors of cholinesterases, up to now maslinic acid has not been part of such studies.For this reason, three series of maslinic acid derivatives possessing modifications at different centers were synthesized and subjected to Ellman's assay to determine their inhibitory strength and type of inhibitory action. While parent compound maslinic acid was no inhibitor in these assays, some of the compounds exhibited an inhibition of acetylcholinesterase in the single-digit micro-molar range. Two compounds were identified as inhibitors of butyrylcholinesterase showing inhibition constants comparable to those of galantamine, a drug often used in the treatment of Alzheimer's disease. Furthermore, additional selectivity as well as cytotoxicity studies were performed underlining the potential of several derivatives and qualifying them for further investigations. Docking studies revealed that the different kinetic behavior within the same compound series may be explained by the ability of the compounds to enter the active site gorge of AChE.

Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents

A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution- and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the b16f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC 50 values between 0.31 and 15.6 μM, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs.

Towards cytotoxic and selective derivatives of maslinic acid

Several novel esters and amides of maslinic acid were prepared. Their evaluation for cytotoxic activity with a panel of human cancer cell lines using a sulforhodamine B (SRB) assay revealed for some of them a noteworthy activity. The results from annexinV-FITC and caspase-assays as well as from DNA laddering experiments provided evidence for an apoptotic cell death. A diacetylated benzylamide (15) induced a G1/G0 arrest in tumor cells. It also displayed an extraordinary cytotoxicity against human ovarian cancer cells but a 300 times lower toxicity for non-malignant primary human fibroblasts.

Maslinic acid derivatives induce significant apoptosis in b16f10 murine melanoma cells

Maslinic acid (2α,3β-dihydroxyolean-12-en-28-oic acid), a natural dihydroxylated pentacyclic triterpene acid isolated from olive-pressing residues, has been investigated together with some of its derivatives regarding the induction of apoptosis in B16F10 melanoma cells. Some of the compounds tested are described in this work, but others come from previous studies. Ten of these derivatives induce over 80% of apoptosis, clearly promoting cell death in B16F10 melanoma. By contrast, the induction cell death through necrosis was very slightly significant with these compounds. These results indicate that maslinic acid derivatives are promising chemopreventive and chemotherapeutic agents.

Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies

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

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.

Pentacyclic triterpenes. Part 1: The first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases

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.