27686-35-7

Upstream product

• 473-98-3 betulin 
• 108-24-7 acetic anhydride 
• 141-78-6 ethyl acetate 

Downstream Products

• 852720-20-8 Phthalic acid mono-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-acetoxymethyl-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl) ester 
• 1234662-03-3 C₃₉H₅₇NO₄ 
• 1239919-26-6 3-[3β-hydroxylup-20(29)-en-28-yloxy]propanenitrile 
• 473-98-3 betulin 
• 1309960-59-5 3β-(2-cyanoethoxy)lup-20(29)-en-28-yl acetate 
• 1309960-47-1 3β,28-di(2-cyanoethoxy)lup-20(29)-ene 
• 4439-98-9 betulonic aldehyde 
• 1620782-34-4 28-acetoxy-3β-(2,3,4,6-tetra-O-benzoyl-α-D-idopyranosyloxy)lup-20(29)-ene 
• 1449483-29-7 28-O-acetyl-3-O'-propargyloxycarbonylbetulin 
• 869747-76-2 C₆₆H₇₈O₁₂ 
• 1721-69-3 betulin diacetate 
• 66252-76-4 28-O-acetylbetulin 3-O-(2',3',4',6'-tetra-O-acetyl-α-D-glucopyranoside) 
• 35823-95-1 28-O-acetylbetulin 3-O-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranoside) 

Relevant academic research and scientific papers

Bismuth triflate-catalyzed Wagner-Meerwein rearrangement in terpenes. Application to the synthesis of the 18α-oleanane core and A-neo-18α-oleanene compounds from lupanes

The use of bismuth(III) salts as catalysts for the Wagner-Meerwein rearrangement of lupane derivatives with expansion of ring E and formation of an additional O-containing ring is reported. This process has also been extended to other terpenes, such as the sesquiterpene (-)-caryophyllene oxide. When the reaction was performed with oleanonic acid, 28,13β-lactonization occurred, without Wagner-Meerwein rearrangement. Under more vigorous reaction conditions, dehydration of the 3β-hydroxyl group and subsequent additional Wagner-Meerwein rearrangement led to the selective synthesis of A-neo-18α-oleanene compounds, in very high yields. The Royal Society of Chemistry 2009.

Enhancement of the antioxidant and skin permeation properties of betulin and its derivatives

This study investigated the antioxidant activity DPPH, ABTS, and Folin–Ciocalteu methods of betulin (compound 1) and its derivatives (compounds 2–11). Skin permeability and accumulation associated with compounds 1 and 8 were also examined. Identification of the obtained products (compound 2–11) and betulin isolated from plant material was based on the analysis of1H-NMR and13C-NMR spectra. The partition coefficient was calculated to determine the lipophilicity of all compounds. In the next stage, the penetration through pig skin and its accumulation in the skin were evaluated of ethanol vehicles containing compound 8 (at a concentration of 0.226 mmol/dm3), which was characterized by the highest antioxidant activity. For comparison, penetration studies of betulin itself were also carried out. Poor solubility and the bioavailability of pure compounds are major constraints in combination therapy. However, we observed that the ethanol vehicle was an enhancer of skin permeation for both the initial betulin and compound 8. The betulin 8 derivative showed increased permeability through biological membranes compared to the parent betulin. The paper presents the transformation of polycyclic compounds to produce novel derivatives with marked antioxidant activities and as valuable intermediates for the pharmaceutical industry. Moreover, the compounds contained in the vehicles, due to their mechanism of action, can have a beneficial effect on the balance between oxidants and antioxidants in the body, minimizing the effects of oxidative stress. The results of this work may contribute to knowledge regarding vehicles with antioxidant potential. The use of vehicles for this type of research is therefore justified.

Isolation, structural modification, and HIV inhibition of pentacyclic lupane-type triterpenoids from cassine xylocarpa and maytenus cuzcoina

As a part of our investigation into new anti-HIV agents, we report herein the isolation, structure elucidation, and biological activity of six new (1-6) and 20 known (7-26) pentacyclic lupane-type triterpenoids from the stem of Cassine xylocarpa and root bark of Maytenus cuzcoina. Their stereostructures were elucidated on the basis of spectroscopic and spectrometric methods, including 1D and 2D NMR techniques. To gain a more complete understanding of the structural requirements for anti-HIV activity, derivatives 27-48 were prepared by chemical modification of the main secondary metabolites. Sixteen compounds from this series displayed inhibitory effects of human immunodeficiency virus type 1 replication with IC50 values in the micromolar range, highlighting compounds 12, 38, and 42 (IC50 4.08, 4.18, and 1.70 μM, respectively) as the most promising anti-HIV agents.

Antineoplastic agents. 595. structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer1

The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7 11 12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/1417 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.

Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin

A new series of betulin derivatives containing one or two pharmacophores bearing an acetylenic and carbonyl function at the C-3 and/or C-28 positions has been synthesized and characterized by 1H- and 13C-NMR, IR, MS and elemental analyses. The crystal structure of 28-O-propynoylbetulin was determined by X-ray structural analysis. All new compounds, as well as betulin, were tested in vitro for their antiproliferative activity against human SW707 colorectal, CCRF/CEM leukemia, T47D breast cancer, and against murine P388 leukemia and Balb3T3 normal fibroblasts cell lines. Most of the compounds showed better cytotoxicity than betulin and cisplatin used as reference agent. 28-O-Propynoylbetulin was the most potent derivative, being over 500 times more potent than betulin and about 100 times more cytotoxic than cisplatin against the human leukemia (CCRF/CEM) cell line, with an ID50 value of 0.02 μg/mL.

Synthesis and biological evaluation of antitumor-active γ-butyrolactone substituted betulin derivatives

The plant triterpenes betulin and betulinic acid (BA) are triterpenes featuring interesting pharmacological properties. Starting from substituted betulinic aldehydes, we used them as lead structures for the synthesis of several γ-butyrolactones and butenolides. Their antitumor activity was examined for 15 cancer cell lines using a SRB-assay and their apoptotic action was documented by trypan-blue test and DNA laddering. Several compounds revealed a higher activity than betulinic acid.

Synthesis and anticancer activity of novel betulinic acid and betulin derivatives

A series of novel betulinic acid derivatives 3-11 and betulin derivatives 12-17 were synthesized. The compounds were characterized by the means of 1H- and 13C-NMR spectroscopy as well as mass spectrometry. The compounds have been tested on ten tumor cell lines of different histogenic origin. The most active derivatives, containing a chloroacetyl group on C-3 in betulinic acid 9 and C-28 in betulin 15, were up to ten times more cytotoxic and many fold more selective towards tumor cells in comparison to normal cells (fibroblasts) than betulinic acid. Furthermore, compound 15 was found to possess cell growth inhibition even when treated for a short time on anaplastic thyroid cancer cells (SW1736).

Synthesis and structure-activity relationship study of cytotoxic germanicane- and lupane-type 3β-O-monodesmosidic saponins starting from betulin

Germanicane-type triterpenes allobetulin (3) and 28-oxoallobetulin (4) can be obtained by the Wagner-Meerwein rearrangement of the more available lupane-type triterpenes betulin (1) and betulinic acid (2), respectively. The medical uses of betulinic acid (2) and its derivatives are limited because of their poor hydrosolubility and pharmacokinetics properties. In order to overcome this major problem, we synthesized and studied the in vitro anticancer activity of a series of 3β-O-monodesmosidic saponins derived from betulin (14-16), betulinic acid (20-22), allobetulin (23-28) and 28-oxoallobetulin (29-34) based on six different natural sugar residues (d-glucose, l-rhamnose, d-arabinose, d-galactose, d-mannose and d-xylose). This structure-activity relationship study confirmed that betulinic acid saponins are generally better in vitro anticancer agents than those derived from betulin with the exception of betulin 3β-O-α-d-mannopyranoside (15) which exerted a potent cytotoxic activity against lung carcinoma (A-549) and colorectal adenocarcinoma (DLD-1) human cell lines with IC50 ranging from 7.3 to 10.1 μmol/L. Furthermore, although the synthesis of novel germanicane-type saponins was carried out with success, the bioactivity measured for these glycosides was not as high as we anticipated since only the 3β-O-β-d-glucopyranoside and 3β-O-β-d-galactopyranoside of allobetulin (23, 24) showed moderate anticancer activity (IC50 30-40 μmol/L).

Activity of lupane triterpenoids from Maytenus species as inhibitors of nitric oxide and prostaglandin E2

In the present study, we report that three new lupane triterpenes (1-3), in addition to 16 known ones (4-19), were isolated from the root bark of Maytenus cuzcoina and the leaves of Maytenus chiapensis. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC). The natural compounds and derivatives 6a, 6b, 9a, and 9b have been tested for potential anti-inflammatory activity, and several compounds including 3-epicalenduladiol (2), 11α-hydroxy- glochidone (3), rigidenol (6), acetoxy-rigidenol (6a), 11α-acetoxy-30- chloro-3-oxo-lup-20(29)-ene (6b), betulin (9), 28-acetoxy-betulin (9a), epibetulin (12), epibetulinic acid (13), and betulonic acid (16) exhibited potent inhibitory effects on NO and prostaglandin E2 production in mouse macrophages (RAW 264.7) stimulated with bacterial endotoxin. The structure-activity relationship is discussed in detail.

Preparation of a 24-nor-1,4-dien-3-one triterpene derivative from betulin: A new route to 24-nortriterpene analogues

A new route to 24-nortriterpene derivatives with 2-hydroxy-δ1,4-cyclohexadieny-3-one A-rings from triterpene precursors has been demonstrated beginning with betulin to prepare derivatives of betulinic acid. The key steps in the transformation are a Suarez cleavage of the A-ring with a subsequent SM12-mediated pinacol-type coupling to reclose the A-ring following removal of the C-24 carbon by oxidative cleavage.