I. P. Baikova

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

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, andp-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.

Synthesis and cytotoxicity of triterpene seven-membered cyclic amines

Abstract3-Deoxy-3a-homo-3a-aza derivatives of betulin and erythrodiol have been synthesized from betulonic and oleanonic acids. 3-Deoxy-3a-homo-3a-aza-28-hydroxy-12(13)-oleanene showed the highest antineoplastic activity of the broad spectrum in vitro; the results of an extensive examination of the derivative in vitro enable one to recommend it for in vivo tests. The modification of the compound in the position C28 by the introduction of a methoxycinnamoyl fragment led to the loss of the antineoplastic activity. As a whole, 3-deoxy-3a-homo-3a-aza derivatives of betulin [3-(aminopropyl)-, 28-(2-carboxyethyl)carboxy-, and 28-cinamoyloxy-] exhibited a moderate antineoplastic activity toward large intestine cancer, breast cancer, and leukemia cells.

Synthesis and antitumor activity of aminopropoxy derivatives of betulin, erythrodiol, and uvaol

Aminopropoxy derivatives of betulin, erythrodiol, uvaol, and oleantriol have been synthesized by the cyanoethylation of the hydroxyl groups of triterpenoids with the subsequent reduction of cyanoethyl fragments. It has been found that 3β,28-di-O-[3-(aminopropoxy)]lupa-20(29)-ene and 3β-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene possess high in vitro antitumor activity toward a wide range of human tumor cell lines. It has been shown that the aminopropoxy fragment is a novel promising pharmacophore group in the synthesis of anticancer agents based on triterpenoids.

Synthesis and cytotoxicity of allobetulin derivatives

A variety of oxygen-, nitrogen-, sulfur-, and platinum-containing allobetulin derivatives, including those with different positions of double bonds in rings A and B, the penta- and hexacyclic ring A, and the 21-acetyl-20,28-epoxy-18α,19βH-ursanoisomeric cycle E, have been synthesized, and the screening of their antineoplastic activity in vitro (cytotoxicity) has been carried out. A significant cytotoxic activity was exhibited by (3R,5R)-19β,28-epoxy-4,5-seco-18α-olean-3(5)-ozonide toward MeWo melanoma cells and by 2,3-indolo-21β-acetyl-20β,28-epoxy-18α,19βH-ursane toward SR leukosis cells. The 3S,5S-diastereoisomer of the former compound showed no cytotoxicity.

Synthesis of triterpenoid acylates: Effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses

The synthesis of a new group of triterpenoid acylates has been conducted on the basis of oleanolic, glycyrrhetic, and ursolic acids and betulin. 28-ortho-Methoxycynnamoylbetulin has been demonstrated to possess high activity against the influenza type A (H1N1) virus with the selectivity index SI > 100 while studying the activity of the synthesized compounds in relation to the reproduction of viral pathogens of respiratory infections. The high activity of 3,28-dinicotinoylbetulin against the papilloma virus (strain HPV-11) was detected with the selectivity index SI 35.The synthesis of a new group of triterpenoid acylates has been conducted on the basis of oleanolic, glycyrrhetic, and ursolic acids and betulin. 28-ortho-Methoxycynnamoylbetulin has been demonstrated to possess high activity against the influenza type A (H1N1) virus with the selectivity index SI > 100 while studying the activity of the synthesized compounds in relation to the reproduction of viral pathogens of respiratory infections. The high activity of 3,28-dinicotinoylbetulin against the papilloma virus (strain HPV-11) was detected with the selectivity index SI 35.

Conjugates of several lupane, oleanane, and ursane triterpenoids with the antituberculosis drug isoniazid and pyridinecarboxaldehydes

Conjugates of betulinic, oleanolic, ursolic, and glycyrrhetic acids and several of their derivatives with the antituberculosis drug isoniazid and 3- and 4-pyridinecarboxaldehydes were synthesized.

Effective synthesis and transformations of Alkyne betulin derivatives

An effective procedure for the synthesis of terminal acetylene derivatives via reaction of methyl ketones with phosphoryl chloride in pyridine was proposed using triterpene betulin as an example. Bisacetylenic triterpenoid was obtained by oxidative self-coupling of 29-norlup-20(30)-yne-3β,28-diyl diacetate.

Effective synthesis of methyl 3β-amino-3-deoxybetulinate

A practical method for preparing methyl 3β-amino-3-dexoybetulinate that is based on column chromatographic separation of 3α- and 3β-t-butoxycarbonates and subsequent removal of the protecting group using formic acid is proposed. The structure of methyl 3β-N-(t-butoxycarbonyl)-3-deoxybetulinate was established by an x-ray structure analysis.

Synthesis of 1,6-Dihydro- and 4-(4-Nitrophenyl)-1,2,3,4-tetrahydropyrimidine, 1H- and 1-Phenyl-1H-pyrazole, and Isoxazole Derivatives on the Basis of Cyclopentanonopimaric Acid

Reactions of cyclopentanonopimaric acid dimethyl ester with phosphoryl chloride, ethyl formate, and p-nitrobenzaldehyde afforded Δ15(16)-16-formyl-15-chloro, 16-hydroxymethylene-15-oxo, and 16-nitrobenzylidene-15-oxo derivatives which were subjected to heterocyclizations to obtain new diterpene pyrimidine, pyrazole, and oxazole derivatives.

Synthesis and hepatoprotector activity of 2-arylidene methylbetulonate derivatives

Betulinic acid (I), representing triterpenoids o f the lupane group, was isolated as long ago as in the beginning of the 20th century [ 1 ]. However, it was not until recent years that this compound drew the attention of pharmacists by showing a broad spectrum of biological activity, including antitumor and antiviral properties [2 8]. Below we report on the synthesis of new 2-arylidene derivatives of betulonic acid methyl ether (Ilia IIIg) obtained by transformation of the triterpenoid A ring. We have also studied the hepatoprotector activity of compounds Illb and llIg. Previously we have demonstrated this type of activity in some betulin esters [9]. Compounds Ilia IIIg were synthesized using the interaction of methylbetulonate (II) with aromatic aldehydes in alcoholic alkali solutions, the products being obtained at a 81 9 0 % yield. The proposed structures of the synthesized compounds were confirmed by data of 1R, UV, and NMR spectroscopies (Tables 1 and 2) and by agreement with the data published for betulonic acid [6, 10, 11], The IR spectra of compounds I l i a IIIg contained, besides the absorption bands characteristic of betulonic acid, the bands at 1610 1600 cm I belonging to vibrations in the aromatic rings. The 13C NMR spectra exhibit additional signals due to carbon atoms of the aromatic substituents (in the region of ~ = 110.5 159.3 ppm), while the signal of C-2 carbon of the aglycon shifts toward weaker fields (from 8 = 33.6ppm for betulonic acid to 131.9137.1 for compounds Ilia IIIg). In the IH NMR spectrum, the proton sig-