2519-35-9

Upstream product

• 85-44-9 phthalic anhydride 
• 473-98-3 betulin 
• 88-99-3 benzene-1,2-dicarboxylic acid 

Relevant academic research and scientific papers

Synthesis of Betulin Dibenzoate and Diphthalate

Betulin-3,28-dibenzoate and -3,28-diphthalate were synthesized for the first time by reacting betulin with melts of benzoic and phthalic acids at 190–200°C for 5 min.

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

METHOD OF PREPARATION OF A SOLUBLE FORMULATION OF WATER-INSOLUBLE PENTACYCLIC AND TETRACYCLIC TERPENOIDS, A SOLUBLE FORMULATION OF A PENTACYCLIC OR TETRACYCLIC TERPENOID AND A PHARMACEUTICAL COMPOSITION CONTAINING THIS SOLUBLE FORMULATION

The invention relates to a method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, wherein the water-insoluble terpenoid having a free carboxylic, hydroxy or amino functional group is derivatized on this functional group with a substituent selected from the group comprising substituents of general formula Xa bound to the hydroxy group of the terpenoid, wherein Xa is -OC-R-COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is -OC-R-COOH, quarternary ammonium substituents of general formula Xb bound to the carboxy group of the terpenoid, wherein Xb is -(CH2)nN+R3Y-, quarternary ammonium substituents of general formula Xc bound to the carboxy group of the terpenoid, wherein Xc je -(CH2)nR+Y-, substituents of general formula Xd bound to the carboxy group of the terpenoid, wherein Xd represents -R-COOH, glycosylic substituents Xe bound by alpha or beta glycosidic bond to the hydroxy group or to the carboxy group of the terpenoid, wherein Xe is selected from the group comprising glucosyl, galactosyl, arabinosyl, rhamnosyl, lactosyl, cellobiosyl, maltosyl and the 2-deoxyanalogues thereof, and subsequently, the prepared derivative is dissolved in the solution containing water, a cyclodextrin and optionally pharmaceutically acceptable auxiliary substances, forming an inclusion derivative with the cyclodextrin. Object of the invention is further a soluble formulation of a pentacyclic or tetracyclic triterpenoid, containing an inclusion complex of the derivatized pentacyclic or tetracyclic terpenoid with a cyclodextrin, and optionally water and pharmaceutically acceptable auxiliary substances and further a pharmaceutical composition containing the soluble formulation.

Synthesis of phthalates of betulinic acid and betulin with cytotoxic activity

Synthesis of 3β-O-phthalic esters from betulinic acid and its esters and synthesis of phthalic esters from betulin and its monoacetates using classical acylation procedure with phthalic anhydride. The evaluation of cytotoxicity of the prepared compounds was using numbers of tumor cell lines in MTT test. It was discovered that hemiphthalic esters had better cytotoxicity than starting compounds as betulinic acid or quite inactive betulin.

The synthesis and hepatoprotective activity of esters of the lupane group triterpenoids

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, and p-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity. Betulin 3,28-bishemiphthalate was more effective than carsil in models of experimental hepatitis caused by carbon tetrachloride, tetracycline, and ethanol.