43124-92-1

Upstream product

• 1721-69-3 betulin diacetate 
• 55029-05-5 lupane-3β,28-diol 
• 108-24-7 acetic anhydride 
• 1721-69-3 betulin diacetate 
• 1072913-62-2 (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol 
• 7372-31-8 Dihydrobetulin 
• 473-98-3 betulin 
• 71-41-0 pentan-1-ol 
• 28161-06-0 3β,28-diacetoxy-29-oxolupane 
• 7803-57-8 hydrazine hydrate 

Downstream Products

• 55029-05-5 lupane-3β,28-diol 
• 139255-65-5 ((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)methyl acetate 
• 7372-31-8 Dihydrobetulin 
• 53900-05-3 3β-Acetoxy-28-lupanol 
• 134501-93-2 17α(H)-28-Norlupane 
• 134501-93-2 17β(H)-28-Norlupane 
• 134502-04-8 3-Oxolupane tosylhydrazone 
• 25576-27-6 Lupanon-⁽³⁾-carbonsaeure-⁽²⁸⁾ 
• 464-99-3 Lupane 
• 3186-72-9 3-Oxolupane 
• 3186-86-5 3β-Hydroxy-28-lupane 
• 203576-62-9 benzyl (3β)-3-hydroxylupan-28-oate 
• 619292-61-4 benzyl 3,O-didehydro-20,29-dihydrobetulinate 
• 25488-54-4 (1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysene-3a-carboxylic acid 

Relevant academic research and scientific papers

First conjugate of glucuronic acid with triterpenoid dihydrobetulin

3β-O-Acetyl-28-O-succinyl-(2,3,4-tri-O-acetyl-5-methoxycarbonyl-β-D-glucopyranosyl)dihydrobetulin was synthesized.

Oxidative Functionalization of Trinor-18α-olean-17(22)-ene Derivatives. Annulation of the E-Ring by an Intramolecular Aldol Reaction

cis-Dihydroxylation of trinor-18α-olean-17(22)-ene 2 with osmium tetroxide led to diol 9. Its cleavage with lead tetraacetate gave tetracyclic ketoaldehyde 10. By comparison, the ozonation of trinor-18α-olean-17(22)-ene 2 in the presence of p-toluenesulfonic acid gave the corresponding ketoacetal 12. Both products were subjected to an intramolecular aldol reaction under the acidic conditions and yielded unusual triterpenes bearing a bicyclo[4.3.1]decane fragment (22). Further manipulation of the protective groups afforded compounds useful in triterpene synthesis, especially in the preparation of potentially biologically active saponins based on a tetracyclic terpene core.

Synthesis and Antimicrobial Activity of Dihydrobetulin N-Acetylglucosaminides

Dihydrobetulin N-acetylglucosaminides were synthesized for the first time. A study of their antimicrobial activity against a standard set of Gram-positive and Gram-negative bacteria and fungi showed highly selective bacteriostatic activity for glycosides 9 and 13 against Staphylococcus aureus ATCC 209p.

Electrosynthesis of Stable Betulin-Derived Nitrile Oxides and their Application in Synthesis of Cytostatic Lupane-Type Triterpenoid-Isoxazole Conjugates

Novel lupane-type triterpenoid-isoxazole conjugates were designed by direct placing of isoxazole linker at C(17) of triterpenoid. The suggested synthetic sequence demonstrates successful combination of electro-organic synthesis and conventional approaches. TEMPO-mediated electrooxidation of betulin to betulinal was developed and optimized at boron-doped diamond anodes with potassium acetate as inexpensive supporting electrolyte. Betulinal-derived oxime was further selectively electro-oxidized at a graphite anode to nitrile oxide, which proved to be stable and isolable species. The same reaction sequence was performed with 3β-lupane-3,28-diol. Nitrile oxides were characterized by 15N NMR and X-ray crystallography. The isolable nitrile oxides allowed creation of isoxazole library by 1,3-dipolar cycloaddition reactions with various alkynes. Some of the title conjugates exhibit cytostatic properties against breast cancer cell line MCF7, glioblastoma multiform cell line U-87 MG and lung carcinoma cell line A549 with growth inhibition (GI50) concentrations up to 11 μm, while being harmless to immortalized human fibroblasts hTERT (GI50 >100 μm).

Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and allobetulin and study of their impact on cancer cells

In this article, we describe the preparation and cytotoxic properties of a small focused library of lupane and 18plusmn;-oleanane triterpenoids that contain a combination of two structural motifs known to enhance the biological activities. First, we introduced two fluorine atoms to position 2 of the skeleton. Second, we synthesized a set of hemiester prodrugs, which were intended to increase the solubility and activity. Starting from betulin, we obtained two hydroxyketones (derivatives of dihydrobetulinic acid and allobetulin) and their fluorination using DAST provided 2,2-difluoro-3-oxo-compounds as the main products. Then the 3-oxo group in each derivative was reduced by NaBH4 to obtain 32-hydroxy compounds suitable for modifying by various hemiesters. We prepared 21 compounds, 11 of them new, their cytotoxicity was tested on T lymphoblastic leukemia CCRF-CEM cells first and the most active derivatives were selected for screening on another six tumor and two non-tumor cell lines. All of them showed selectivity against cancer lines with therapeutic index between 2 and 8. All hemiesters had activity in the same range as the free hydroxyl derivatives and they would be suitable prodrugs for future in vivo experiments. Interestingly, all hemiesters of 2,2-difluorodihydrobetulonic acid had higher activity against p53 knock-out p53g'/g' cancer cell line than against the non-mutated analog. In active derivatives, the cell cycle was analyzed by flow cytometry and several compounds slowed down cell cycle progression through G0/G1 or S-phase.

Novel betulin derivatives as antileishmanial agents with mode of action targeting type IB DNA topoisomerase

Toward developing antileishmanial agents with mode of action targeted to DNA topoisomerases of Leishmania donovani, we have synthesized a large number of derivatives of betulin. The compound, a natural triterpene isolated from the cork layer of Betula spp. plants exhibits several pharmacological properties. Three compounds (disuccinyl betulin, diglutaryl dihydrobetulin, and disuccinyl dihydrobetulin) inhibit growth of the parasite as well as relaxation activity of the enzyme type IB topoisomerase [Leishmania donovani topoisomerase I (LdTOP1LS)] of the parasite. Mechanistic studies suggest that these compounds interact with the enzyme in a reversible manner. The stoichiometry of these compounds binding to LdTOP1LS is 1:1 (mole/mole) with a dissociation constant on the order of ～10-6 M. Unlike CPT, these compounds do not stabilize the cleavage complex; rather, they abrogate the covalent complex formation. In processive mode of relaxation assay condition, these compounds slow down the strand rotation event, which ultimately affects the relaxation of supercoiled DNA. It is noteworthy that these compounds reduce the intracellular parasite burden in macrophages infected with wild-type L. donovani as well as with sodium antimony gluconate resistant parasite (GE1). Taken together, our data suggest that these betulin derivatives can be exploited as potential drug candidates against threatening drug resistant leishmaniasis. Copyright

Oxyfunctionalization of unactivated C-H bonds in triterpenoids with tert-butylhydroperoxide catalyzed by meso-5,10,15,20-tetramesitylporphyrinate osmium(II) carbonyl complex

A system consisting of meso-5,10,15,20-tetramesitylporphyrinate osmium(II) carbonyl complex [Os(TMP)CO] as a precatalyst and tert-butylhydroperoxide (TBHP) as an oxygen donor is shown to be an efficient, regioselective oxidant system for the allylic oxidation, ketonization and hydroxylation of unactivated C-H bonds in a series of the peracetate derivatives of penta- and tetracyclic triterpenoids. Treatment of the substrates with this oxidant system afforded a variety of novel or scarce oxygenated derivatives in one-step. Structures of the isolated components, after chromatographic separation, were determined by spectroscopic methods including GC-MS and shift-correlated 2D-NMR techniques. Factors governing the regioselectivity and the possible mechanism for the oxyfunctionalization of the unactivated carbons are also discussed.

Triterpenoid derivatives

The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, crystal form, complex, hydrate, or hydrolysable ester thereof, in the preparation of a medicament for treating a patient suffering from leukaemia, cancer or other proliferative disorder. A further embodiment relates to the use a compound of formula (I) in an assay for detecting the phosphorylation state of cellular substrates. The present invention also relates to novel compounds of formula (I), and the chemical synthesis thereof.

Synthesis of glycosides of lupane-type triterpene acids

A preparative synthesis of glucosides of the lupane-type triterpene acids betulinic, dihydrobetulinic, betulonic, dihydrobetulonic, and 3,20-dioxo-30-norlupan-28-oic was proposed. Glycosylation of 3-hydroxyacids by α-acetobromoglucose (ABG) with Ag2O was performed in pyridine (Py) to form glycosides at C-28, repeated glycosylation of which by these same reagents but in CH2Cl2 generated a glycoside bond at C-3 to form bisglucosides. 28-Glucosides of ketoacids were formed in high yields in both Py and CH2Cl2.

Montmorillonite clay catalysis. Part 10. K-10 and KSF-catalysed acylation of alcohols, phenols, thiols and amines: Scope and limitation

Montmorillonite K-10 and KSF are highly efficient catalysts for the acetylation of a variety of alcohols, thiols, phenols and amines with acetic anhydride. Amino groups can be selectively acetylated in the presence of hydroxy groups, while the hydroxy groups can be preferentially acetylated in the presence of thiol groups. No selectivity is observed between primary and secondary hydroxy groups in the presence of K-10 and KSF. The catalysts are found not to be efficient for acetylation of tertiary alcohols. This method is simple and convenient with minimum environmental impact. The catalysts are also effective for the acylation of alcohols, thiols, phenols and amines with acetyl chloride and benzoyl chloride. Cyclic anhydrides such as succinic anhydride, maleic anhydride and phthalic anhydride and p-toluene sulfonyl chloride show less reactivity than acetic anhydride and acyl chlorides.