Synthesis of 30-Amino Derivatives of Lupane Triterpenoids

Uzenkova, N. V.; Petrenko, N. I.; Шакиров, М. М.; Шульц, Э. Э.; Толстиков, Г. А.

doi:10.1007/s10600-006-0014-9

Cited by 18 publications

(9 citation statements)

References 9 publications

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“…Betulonic acid was obtained in the chromic acid oxidation from betulinic acid (Urban et al 2007). The treatment of betulinic acid and the betulinic acid acetate with excess ethereal diazomethane solution rendered the corresponding methyl ester and derivatives (Urban et al 2005;Uzenkova et al 2005). All compounds were purified by column chromatography and showed 1 HNMR and 13 CNMR spectra in accordance with literature previously cited.…”

Section: Methodsmentioning

confidence: 99%

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

et al. 2009

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Malaria is one of the most important tropical diseases and mainly affects populations living in developing countries. Reduced sensitivity of Plasmodium sp. to formerly recommended antimalarial drugs places an increasing burden on malaria control programs as well as on national health systems in endemic countries. The present study aims to evaluate the antimalarial activity of betulinic acid and its derivative compounds, betulonic acid, betulinic acid acetate, betulinic acid methyl ester, and betulinic acid methyl ester acetate. These substances showed antiplasmodial activity against chloroquine-resistant Plasmodium falciparum parasites in vitro, with IC(50) values of 9.89, 10.01, 5.99, 51.58, and 45.79 microM, respectively. Mice infected with Plasmodium berghei and treated with betulinic acid acetate had a dose-dependent reduction of parasitemia. Our results indicate that betulinic acid and its derivative compounds are candidates for the development of new antimalarial drugs.

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Section: Methodsmentioning

confidence: 99%

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

et al. 2009

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“…The synthesis of derivatives 22 and 23 (Scheme 1) began with the methoxylation of the isopropenyl group of the commercially available compound 1 in two steps, as previously described. 31 In the first step the reaction of betulin diacetate 6 with N-bromosuccinimide (NBS) in CCl 4 produced a 30-bromo derivative which was further hydrolyzed by NaOH (4 M) in a MeOH:THF mixture, at room temperature, to afford the 30-methoxy derivative 7 and the 30-bromo compound 8. The ratio of compounds 7 and 8 was dependent on the reaction conditions used.…”

Section: Chemistrymentioning

confidence: 99%

“…Modifications of the parent structure of these compounds at these positions can produce potentially important derivatives, found to be more effective than the starting ones, thus making them appealing for further development as antitumour drugs. 18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Nitrogen-containing derivatives of 1 and 2, such as Betulin 1: R = CH 2 OH Betulinic acid 2: R = COOH amine derivatives, 21,23,35 oxime derivatives, 21,23,30 amino acid conjugates, 22 amide derivatives, 20,32 hydrazine 29 and hydrazone derivatives, [28][29][30]35 imidazolide derivatives, 37 and other N-heterocyclic derivatives 24,31,34,36 have been reported to possess antiproliferative effect against tumour cell lines.…”

Section: Introductionmentioning

confidence: 99%

Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity

Santos

Salvador

Marín

et al. 2009

Bioorganic & Medicinal Chemistry

110

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“…Betulin was isolated from Betula pendula bark by the literature method [30]. Betulin O-vinyl ether 8 was prepared as before [24]; bromomethyl ester 13, by the literature method [8]; betulinic acid methyl ester, by the literature method [31]. Anhydrous MeCN was prepared by distillation over P 2 O 5 and then over CaH 2 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Sulfobetaines Based on Betulinic Acid and its Esters

et al. 2015

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Methods for preparing sulfobetaines of betulinic acid that contained N,N-(dimethylammonium)butane-1-sulfonate, a new type of Zwitter-ion in a series of lupane-type pentacyclic triterpenoids, were developed in order to prepare new betulinic acid derivatives and to study the structure-biological-activity relationship.Keywords: betulinic acid, 1,4-butane sultone, sulfobetaine.Betulinic acid is the lead compound among lupane-type pentacyclic triterpenoids and is interesting as a platform for developing drugs with antitumor, antiviral, antimicrobial, and other types of pharmacological activity [1][2][3][4][5]. Recently, a series of ionic betulinic-acid derivatives such as ammonium and triphenylphosphonium salts were synthesized. They exhibited significantly higher antitumor and antimicrobial activity than the acid itself [6][7][8][9][10][11][12][13]. Sulfobetaine derivatives of betulinic acid and other lupane-type pentacyclic triterpenoids have not been reported despite the frequent use of the biomimetic sulfobetaine group to design biologically active compounds with antibacterial, antiviral, and antiproliferative properties; to increase the solubility of hydrophobic compounds; and also to construct nanocarriers for targeted drug delivery [14][15][16][17][18][19][20][21].New derivatives of betulinic acid (1) were prepared and their structure-biological-activity relationship was studied using the synthetic method developed by us for betulinic-acid sulfobetaines 2-4, a new class of lupane-type pentacyclic triterpenoids containing N,N-(dimethylammonium)butane-1-sulfonate bonded to the C-3 or C-28 position of the triterpene backbone.Sulfobetaines 2-4 were prepared by treating the corresponding triterpene C-3 or C-28 tertiary amine of 5-7 with commercially available 1,4-butane sultone [22,23]. Betulinic acid C-3 tertiary amine 5 was synthesized by acylating the C-3-OH of betulin 28-O-vinyl ether with chloroacetic acid (DCC, DMAP) and oxidizing in two steps the resulting betulin 3E-chloroacetate (9) with pyridinium chlorochromate (PCC) to give the corresponding aldehyde, which was reacted immediately after flash chromatography with NaClO 2 to obtain the 3E-chloroacetate of acid 10. Amination of 10 with an excess of N,N-dimethylamine (40% aqueous) gave tertiary amine 5 in 93% yield. C-28-O-Vinyl ether 8, which was prepared by us earlier via vinylation of betulin with acetylene in KOH-DMSO superbase [24], turned out to be a convenient intermediate for synthesizing betulinic acid 3E-chloroacetate 10. O OR 2 O 1 -4 N O SO 3 X = + _ N SO 3 _ + Y = 1: R 1 = R 2 = H; 2: R 1 = X, R 2 = H 3: R 1 = X, R 2 = Me; 4: R 1 = H, R 2 = Y

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Synthesis of 30-Amino Derivatives of Lupane Triterpenoids

Cited by 18 publications

References 9 publications

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice

Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity

Synthesis of Sulfobetaines Based on Betulinic Acid and its Esters

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