E. E. Shults

Synthesis of Betulonic Acid Derivatives Containing Amino-Acid Fragments

New derivatives of betulonic acid containing on C-28 fragments of amino acids or their methyl esters were prepared as potential biologically active agents.

Synthesis of 30-amino derivatives of lupane triterpenoids

New derivatives of betulin and betulinic acid containing various amines on C-30 that are of interest as potentially biologically active agents were prepared.

Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity.

A series of 2-(4-R-triazolyl)substituted 3-oxo-2,3-dihydrofurocoumarins have been synthesized by a regioselective cycloaddition of 2-azidooreoselone 1 or 2-azido-9-[(4-methylpiperazin-1-yl)methyl]oreoselone 2 with various alkynes in the presence of Cu(II)/ascorbate in water/methylene chloride reaction medium. The structure of 2-azidooreoselone was established by X-ray structure analysis. The cytotoxicity of 2-substituted dihydrofurocoumarins was determined against three cancer cell lines (CEM-13, MT-4, U-937) using the conventional MTT assays. Among the tested molecules, most of the analogs displayed better cytotoxic activity then the parent natural furocoumarin peucedanin 3. The activity and selectivity to the cell line increased even further in the series of 2-(4-{2,3-dihydrobenzo[b][1,4]dioxine}triazolyl)-3-oxo-2,3-dihydrofurocoumarins and 2-(4-aryltriazolyl)-3-oxo-2,3-dihydrofurocoumarins having the (4-methylpiperazin-1-ylmethyl) substituent in the 9-th position. The most active compound 20 contain the 4-hydroxy-3-methoxybenzamidomethyl substituent in the 4-th position at the triazole ring of 2-(triazol-1-yl)dihydrofurocoumarins. The obtained 2-triazolyl substituted dihydrofurocoumarins were studied as inhibitors of phosphodiesterase (PDE-4B) using docking experiments. As a result of virtual screening 3 compounds are selected based on minimum binding energy. The interactions of the most active compound and amino acid residues in the binding site were studied.

Synthetic transformations of methylenelactones of eudesmanic type. Behavior of isoalantolactone under the conitions of heck reaction

By Heck reaction of isoalantolactone with aryl bromides or aryl iodides (3aR,4aS, 8aR,9aR,E)-3-arylmethylidene-8a-methyl-5-methylidenedecahydronaphtho[2,3-b]furan-2(3H)-ones and (4aS,8aR,9aS)-3-arylmethyl-8a-methyl-5-methylidene-4a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(4H)-ones, products of the double bond shift, were synthesized. The yields of the arylation products depend on the nature of the catalytic system and on the structure of the aryl halide. The structures of (3aR,4aS,8aR,9aR,E)-3-(3,4-dimethoxybenzylidene)-8amethyl-5-methylidenedecahydronaphtho[2,3-b]furan-2(3H)-one and (4aS,8aR,9aS)-3-(2-methylsulfanylbenzyl)-8amethyl-5-methylidene-4a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2(4H)-one were proved by XRD analysis.

Effect of nitrogen-containing derivatives of the plant triterpenes betulin and glycyrrhetic acid on the growth of MT-4, MOLT-4, CEM, and Hep G2 tumor cells

Derivatives of the available plant triterpenes glycyrrhetic acid and betulin (betulin succinates and amides of betulonic and 18β-glycyrrhetic acids containing fragments of long-chain amino acids and a peptide) were synthesized. The inhibitory action of these compounds on the growth of MT-4, MOLT-4, CEM, and Hep G2 tumor cells and their effect on the apoptosis of these cells were studied. It was shown that betulonic acid amides are more effective inhibitors of the tumor cell growth than the corresponding amides of glycyrrhetic acid. It was also found that betulonic acid amides containing fragments of caprylic, pelargonic, and undecanoic acids are more effective inhibitors of tumor cell growth than betulinic acid. The 17-dipeptide derivative of betulonic acid N-{N-[3-oxo-20(29)-lupen-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid exhibited the maximum inhibitory activity toward the tumor cells studied. Data on the induction of apoptosis in tumor cells by betulin derivatives at a concentration of 10 μg/ml were obtained by flow cytometry. The amides of betulonic acid proved to be the most effective inducers of apoptosis.

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

Summary Two new triterpenoid saponins 1 and 2 were isolated from the methanol extract of the roots of Acanthophyllum gypsophiloides Regel. These saponins have quillaic acid or gypsogenin moieties as an aglycon, and both bear similar sets of two oligosaccharide chains, which are 3-O-linked to the triterpenoid part trisaccharide α-L-Arap-(1→3)-[α-D-Galp-(1→2)]-β-D-GlcpA and pentasaccharide β-D-Xylp-(1→3)-β-D-Xylp-(1→3)-α-L-Rhap-(1→2)-[β-D-Quip-(1→4)]-β-D-Fucp connected through an ester linkage to C-28. The structures of the obtained saponins were elucidated by a combination of mass spectrometry and 2D NMR spectroscopy. A study of acute toxicity, hemolytic, anti-inflammatory, immunoadjuvant and antifungal activity was carried out. Both saponins 1 and 2 were shown to exhibit immunoadjuvant properties within the vaccine composition with keyhole limpet hemocyanin-based immunogen. The availability of saponins 1 and 2 as individual pure compounds from the extract of the roots of A. gypsophiloides makes it a prospective source of immunoactive agents.

Study of alkaloids of the Siberian and Altai flora 14. Synthesis of alkaloid-based tertiary N-(3-arylprop-2-ynyl)amines

Abstract3-Arylprop-2-ynylamines containing the key fragment of known alkaloids of the Altai flora were synthesized by the Sonogashira and Mannich reactions.

Synthesis of 5-Aryl-1,4-naphthoquinone and 1-Aryl-9,10-anthraquinone Derivatives by Cycloaddition of 1-(Dimethoxyphenyl)-3-trimethylsiloxy-1,3-butadienes to 1,4-Benzoquinones and 1,4-Naphthoquinones

The Diels-Alder reaction of new 1-(3,4-dimethoxyphenyl)- or 1-(2,4-dimethoxyphenyl)-2-R-3-trimethylsiloxy-1,3-butadienes with 2,5- and 2,6-dibromo-, and 2-bromo-6-methyl-1,4-benzoquinones regioselectively yields substituted 7-hydroxy-5-(dimethoxyphenyl)-1,4-naphthoquinones. By cycloaddition of the siloxydienes to naphthoquinone, bromonaphthoquinone, and juglone the corresponding substituted 3-hydroxy-1-(dimethoxyphenyl)-9,10-anthraquinones or their 4,4a-dihydro or 1,1a,4,4a-tetrahydro derivatives were obtained.

Study of plant coumarins. 12*. Synthesis of 2-(1,2,3-triazolyl)-modified furocoumarins

Bromooreoselone reacted with sodium azide to give 2-azidooreoselone, which was highly reactive in a catalytic Huisgen reaction with various terminal alkynes. These reactions yielded 4-substituted 2-(triazol-1-yl)furocoumarins. The reaction of oreoselone azide with dimethyl acetylene-1,2-di-carboxylate gave 2-[(4,5-dimethoxycarbonyl)triazolyl]oreoselone and reaction with 7-ethynyl-6-methoxycarbonylcoumarin gave 1,4-dicoumarin-substituted 1,2,3-triazole.

Study of plant coumarins: X. Peurutenicin triflate in cross-coupling reactions

By Suzuki cross-coupling reaction of peurutenicin triflate with arylboric, furanylboric, pyridinylboric, and indolylboric acids the corresponding 7-aryl(hetaryl)coumarins were synthesized. The high activity of hetaryl-substituted boric acids in the Suzuki reaction was observed. Heck reaction of 7-O-trifluoromethylsulfonylpeur utenicin with terminal olefins (styrene, vinylpyridines, vinylpyrazine, vinyltriazole) was used to prepare (E)-7-[aryl(hetaryl)vinyl]coumarins. The dependence of reaction products yield on the nature of the catalytic system was found.