1721-57-9

Upstream product

• 186581-53-3 diazomethane 
• 4339-72-4 oleanolic acid acetate 
• 508-02-1 oleanolic acid 
• 140479-92-1 (4aS,6aS,6bR,8aR,9R,10S,12aR,14bS)-10-Acetoxy-2,2,6a,6b,9,12a-hexamethyl-9-methylsulfanylthiocarboxyoxymethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carboxylic acid methyl ester 
• 1721-78-4 hederagenin methyl ester 
• 4339-72-4 oleanolic acid 3-acetate 
• 51-92-3 tetramethylammonium 
• 1724-17-0 oleanolic acid methyl ester 
• 108-24-7 acetic anhydride 
• 508-02-1 Oleanolic acid 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 67-56-1 methanol 
• 74-88-4 methyl iodide 
• 85031-73-8 (3β,12α) 3,12-diacetoxy-olean-28-oic acid 28,13-lactone 

Downstream Products

• 25493-94-1 methyl 3-O-β-acetyl-11-dehydro-12-oxo-18β-oleanolate 
• 73493-60-4 3-oxo-28-norolean-12-ene 
• 19897-41-7 3β-hydroxy-11α,12α-epoxy-olean-28,13β-olide 
• 35738-25-1 11α,12α-epoxy-oleanan-28->13-olide-3β-yl acetate 
• 1724-17-0 oleanolic acid methyl ester 
• 15071-78-0 methyl 3-O-β-acetyl-11-oxo-18β-oleanolate 
• 508-02-1 Oleanolic acid 
• 85541-82-8 methyl 5-androsten-3β-ol-17β-carboxylate 
• 1415383-65-1 (4aS,6aS,6bR,8aR,12aR,14bS)-benzyl 14-(3-aminophenyl)-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 
• 1415383-66-2 (4aS,6aS,6bR,8aR,12aR,14bS)-benzyl 14-(3-aminophenyl)-11-cyano-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 
• 218600-53-4 bardoxolone methyl 
• 218600-50-1 methyl 3,12-dioxoolean-9⁽¹¹⁾-en-28-oate 
• 65023-20-3 methyl 3β-acetoxy-12-oxoolean-9(11)-en-28-oate 

Relevant academic research and scientific papers

Synthesis of erythrodiol C-ring derivatives and their activity against Chlamydia trachomatis

To develop new potential agents against Chlamydia trachomatis among oleanane type triterpenoids the synthesis, spectral and X-ray analysis as well as antimicrobial screening of C-12 oxygen and nitrogen derivatives of erythrodiol is presented. The reduction of methyl 3β-acetoxy-12-oxo-oleanoate with LiAlH4 led to isomeric erythrodiol 12β- and 12α-hydroxy-derivatives, their stereochemistry with respect to the position of hydroxyl-group at C-12 was determined based on the multiplets splitting patterns, the magnitude of the spin–spin interaction, and NOESY interactions. Methyl 3β-acetoxy-12-oxo-oleanoate was transformed to 12E-hydroxyimino- and 12E-methoxyimino-derivatives by the interaction with NH2OH?HCl or CH3ONH2?HCl, respectively. By Beckmann rearrangement with SOCl2 in dioxane 12E-oxime was converted to C-lactame and its following reduction with LiAlH4 in THF or dioxane led to erythrodiol C-azepanone or C-azepane derivatives. The structure 3-O,12-N-bis-acetyl-derivative of C-azepane-erythrodiol was confirmed by the single crystal X-ray analysis. Erythrodiol 12β-hydroxy- and C-azepane derivatives were found to be lead compounds with significant activity against C. trachomatis with MIC 1.56 and 3.125 μg/mL. Molecular docking was employed to suggest potential binding interaction, the tested compounds are likely to act as Cdu1 protein inhibitors while 12β-hydroxy-erythrodiol exhibited the highest affinity towards this respective target protein. These results indicated that C-ring oxygen and nitrogen erythrodiol derivatives might be considered for further research in the design of antibacterial agents against Chlamydia trachomatis.

Total synthesis method of meroterpenoid natural product (+)-Arisugacins F/G

The invention discloses a total synthesis method of a meroterpenoid natural product (+)-Arisugacins F/G, and belongs to the field of organic synthesis. The method is as follows: using oleanolic acid as a chiral source starting raw material, and carrying out active group protection, free radical elimination, ring-opening reaction, cis-trans isomerization and oxidative hydrolysis to obtain a chiralintermediate aldehyde; then carrying out [3 + 3] cycloaddition reaction with pyrone, and carrying out hydrogenation reduction to generate (+)-Arisugacins F; and then carrying out an oxidation reactionto obtain (+)-Arisugacins G. According to the invention, the chiral source starting raw material oleanolic acid is commercially available, the reaction conditions of each unit in the reaction processare mild and controllable, the stereoselectivity of the key reaction is strong, and the method has potential application value in total synthesis of terpenoid natural products and drug discovery.

Total syntheses of (+)-arisugacins F, G

(+)-Arisugacin F and G are synthesized from commercially available oleanolic acid in 9 and 10 steps, respectively. This strategy features a AgOTf/Pd(PPh3)4-mediated cis/trans olefin isomerization and a highly convergent formal oxa-[3 + 3] cycloaddition between key α, β-unsaturated aldehyde and pyrone, which lays the foundation for efficient and concise synthesis of other natural products with similar terpenoid scaffolds.

Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential

Triterpenoids are in the focus of scientific interest, and they were evaluated for many pharmacological applications among them their ability to act as inhibitors of cholinesterases. These inhibitors are still of interest as drugs that improve the life quality of patients suffering from age-related dementia illnesses especially of Alzheimer's disease. Herein, we prepared several derivatives of ursolic and oleanolic acid and screened them in Ellman's assays for their ability to inhibit acetylcholinesterase and/or butyrylcholinesterase, and for each of the active compounds the type of inhibition was determined. As a result, several compounds were shown as good inhibitors for acetylcholinesterase and butyrylcholinesterase even in a micromolar range. An ursolic acid derived hydroxyl-propinyl derivative 10 was a competitive inhibitor for butyrylcholinesterase with an inhibition constant of Ki = 4.29 μM, and therefore being twice as active as gold standard galantamine hydrobromide. The best inhibitor for acetylcholinesterase, however, was 2-methyl-3-oxo-methyl-ursoloate (18), acting as a mixed-type inhibitor showing Ki = 1.72 μM and Ki′ = 1.28 μM, respectively.

Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement

Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and HA22T/VGH of hepatocarcinoma, a strongly aggressive tumor that is not responsive toward the standard therapies. New derivatives containing a three carbons side chain on the C-3 position were synthetized in both stereoisomeric forms by the Barbier-Grignard procedure and three of them were found to be active toward all of the three targets. The implication of the transcriptional nuclear factor NF?κB in the mechanism of action was assessed for the more active compounds in the set, as hepatocellular carcinoma (HCC) cyto-types are known to overexpress NF?κB.

Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A "visible Light" Approach

In our continued effort to address the challenges of selective sp3 C-H fluorination on complex molecules, we report a sensitized aliphatic fluorination directed by terpenoidal enones using catalytic benzil and visible light (white LEDs). This sensitized approach is mild, simple to set up, and an economical alternative to our previous protocol based on direct excitation using UV light in a specialized apparatus. Additionally, the amenability of this protocol to photochemical flow conditions and preliminary evidence for electron-transfer processes are highlighted.

Multiple Enone-Directed Reactivity Modes Lead to the Selective Photochemical Fluorination of Polycyclic Terpenoid Derivatives

In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp3 C-H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.

Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites

Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

Synthesis of ring-C modified oleanolic acid derivatives and their cytotoxic evaluation

Ring-C of oleanolic acid was chemically modified by treating with NBS under a variety of experimental conditions. The structures of the synthesized compounds were established by spectral analysis (1H &13C NMR and Mass). All the compounds were evaluated against a panel of five human cancer cell lines by using MTT assay. Among the tested compounds, 2 and 7 showed significant activity against breast cancer cell line, MCF-7. Most significantly, compound 7 showed several folds enhanced activity against MCF-7 cancer cell lines (IC50: 2.96?μM) than that of the parent (1) and the intermediate compound (6). Flow cytometric analysis revealed that these compounds arrested the cell cycle in G0/G1 phase and induced mitochondrial mediated apoptosis.

The chemical and biological potential of C ring modified triterpenoids

A convenient and elegant route has been developed to separate the natural regioisomers triterpenoids ursolic acid (UA) and oleanolic acid (OA) as well as derivatives thereof. Eleven unknown derivatives of OA were designed, synthesized, and their cytotoxicity was investigated. Further sixteen compounds were prepared to correlate all compounds in a SAR study. It could be shown that C-ring modifications of OA and UA have only a moderate influence onto the cytotoxic activity of the compounds but a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780).