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Efficient and versatile synthetic procedures towards novel derivatives of betulonic acid via Mannich reaction, Sonogashira cross-coupling, and copper(i)-catalyzed 1,3-dipolar cyclo-additions were developed. Introduction of secondary amines (Mannich reaction) into betulonic acid amides led to derivatives possessing marked spasmolytic activity, which is not characteristic of the triterpene fragment.

Synthesis of lupane C28-imidazolides, contained 3-oxo-, 3-oximino- and 2-cyano-2,3-seco-4(23)-en-frag ments in cycle A was carried out. The most antitumor activity at. in vitro testing showed 3-oximino-lup- 20(29)-en-28-yl-1H-imidazole-1-carboxylate; which inhibited the growth or induced apoptosis of non-small lung cancer, colon cancer, breast cancer, CNS cancer, ovarian cancer, prostate cancer, leucosis, melanoma cells. In experiments in mice its moderate antitumor activity against grafted breast adenocarcinoma Ca 755 and adenocarcinima of colon was observed.

Research from the last 20 years on the use of ozonolysis of cyclic and acyclic mono- and dienes and aromatic compounds in various steps of the total synthesis of insect pheromones and juvenoids was reviewed.

Here we report on new versions of this reaction by the examples of adamantanolactone (XII), β-campholide (XIII), caranolactone (XIV), and also allobetulonolactone (XV) and norallobetulonolactone (XVI) obtained from betulin [3]. At the reduction of adamantanolactone (XII) isobutylacetal (VII) formed in 60% yield. β-Campholide (XIII) afforded a diastereomeric mixture (58 : 42 according to Н NMR data) of acetal VIII. In the stereochemical assignment of the NMR spectra of compound VIII the chemical shift values of the bridgehead carbon atoms (С, С) and those in the bottom of the boat (С, С), and also the chemical shifts and coupling constants of the anomeric proton Н are informative. Relatively downfield signals of the mentioned atoms С (~δ 1–2.5 ppm), and also more upfield shift of the anomeric proton Н at 5.06 ppm and a large value of J3,4 5.3 Hz indicate the equatorial orientation of the i-BuО group in the prevailing stereoisomer. According to Н NMR data compound IX formed as a mixture (3 : 1) of epimers with respect to asymmetric acetal center. The value J2,3 8.9 Hz of the anomeric proton in the predominant stereoisomer indicates its axial orientation and consequently the equatorial position of the isobutoxy group.

Reaction of 5-methoxy-substituted salicylic aldehydes containing in the position 3 tert-butyl, 2-phenylpropan-2-yl, or 1-phenylethyl groups with m- and p-allyloxy-, (but-3-enyloxy)-, (pent-4-enyloxy)anilines without solvent in an open system at 130°C afforded a series of (N-aryl)salicylaldimines L that with TiCl2 (OPr-i)2 formed complexes of titanium(IV) dichloride L2TiCl2.

Hydrochlorides of hydroxylamine and semicarbazide efficiently reduce peroxide products of olefin ozonolysis in a system CH2Cl2-AcOH leading to the formation of carboxylic acids and their derivatives. The application of water as the solvent component favors the increase in the fraction of nitrogen-containing organic compounds (semicarbazones, keto- and aldoximes, nitriles) and reduction in the yield of carboxylic acids.

Anti-inflammatory activity of amides of levopimaric acid (LpA) with acetylenic moiety and its esters with 4-R-triazolic substitutions was investigated using histamine-induced mice paw edema model. The synthesized LpA derivatives possess anti-inflammatory activity comparable to the activity of indomethacin.

Treatment with hydroxylamine and semicarbazide hydrochlorides of peroxide products obtained by ozonolysis of olefins in tetrahydrofuran gives mainly carboxylic acids and their derivatives.

Griesbaum ozonolysis of mixtures of methyl 3-(methoxyimino)-5β-cholan-24-oate with ketones (cyclohexanone, methyl trifluoromethyl ketone, and phenyl trifluoromethyl ketone) afforded for the first time steroidal 1,2,4-trioxolanes which were isolated as mixtures of stereoisomers.

Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety.

Cardioprotective effect of resveratrol and resveratroloside was determined in ischemia-reperfusion experiments on rats. It was found that single intraperitoneal administration of any compound (10 mg/kg) followed by 30-min ischemia and 120-min reperfusion resulted in statistically significant decrease of myocardial infarct area (55.0±4.0% for control group; 40.7±4.4% for the group 1 received resveratrol; 41.6±4.8% for the group 2 received resveratroloside). The cardioprotective effect of resveratroloside was detected for the first time.

Ozonolysis of (1R,3R)-p-menth-4-en-3-ol in methylene chloride or methanol in the presence of pyridine afforded a mixture of equimolar amounts of epimeric 1-[(2R,4S,6S)- and 1-[(2S,4S,6S)-6-hydroxy-4-methyltetrahydro-2H-pyran-2-yl]-2-methylpropan-1-ones. A probable reaction mechanism is discussed.

Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the C-ring, displays anti-inflammatory and inhibitory activities with respect to tumor cells with a high selectivity index value.

Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)2 in the presence of Cu(OAc)2, p-benzoquinone in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)-16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid.

Peroxide products of partial ozonolysis of (S)-(-)-limonene (ee 50%) in cyclohexane-methanol at 2–4°C were treated with a solution of HCl in methanol, which led to the formation of a 4: 1 mixture of methyl [(1S)-2,4-dimethoxy-2,4-dimethylcyclohexyl]acetate and [(1S)-2,4-dimethoxy-2,4-dimethylcyclohexyl]acetaldehyde, each being represented by a single pair of diastereoisomers at a ratio of 3: 1.

Hydroxylamine and semicarbazide hydrochlorides were shown to be efficient as reducing agents toward peroxide products of ozonolysis of various olefins with different degrees of substitution. The rate of the transformations aldehyde → aldehyde oxime → nitrile → ester upon treatment of peroxides with hydroxylamine hydrochloride in isopropyl alcohol was lower than in methanol.

Transformations of peroxide products of ozonolysis of various olefins with different degrees of substitution at the double bond by the action of hydroxylamine and semicarbazide hydrochloride in methanol in the presence of water as co-solvent were studied.

New derivatives of betulin, betulinic acid methyl ester, and their acetate analogs containing 1,2,3-triazole fragments in the C-30 position were synthesized. It was shown using the Ames test that 30-azidolup-20(29)-enes and 3β,28-diacetoxy-30-(4-R-1,2,3-triazol-1-yl)lup-20(29)-enes did not exhibit mutagenic properties.

16-(1-R-1,2,3-Triazol-4-ylethyl)-, 16-(1-R-1,2,3-triazol-4-ylmethoxymethyl)-, and 16-{2-(1-R-1,2,3-triazol-4-yl)-1-[(1-R-1,2,3-triazol-4-ylmethoxy)ethyl]}-substituted derivatives of methyl lambertianate were synthesized by 1,3-cycloaddition of labdanoid alkynes with azides. The compounds obtained possess considerable cytotoxicity toward the human tumor cell lines CEM-13, MT-4, and U-937. The most active compound, methyl 16-(2-{2-[(1-benzyl-1H-1,2,3-triazol-4-yl)acetyl]furan-3-yl}ethyl)lambertianate, was found to inhibit the viability of the tumor cells by 50% (CCID50) in the concentration of 7–12 μmol L−1.

The object of this study is the interaction of the cyclic anhydride 2 of (18α,19β)-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone (1) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2-amino-2-oxo-3-oic acids=2-amides) were formed solely upon the opening of the anhydride cycle by secondary amines (Scheme 2), whereas the interaction with primary amines yielded a mixture of isomeric amides (Scheme 10). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4-methoxybenzylamine. The interaction between the resulting 3-amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2-amides formed spiropyrrolidinetriones (Scheme 4).

A series of (N-aryl)salicylaldimines was synthesized by the reaction of salicylaldehydes substituted in the positions 3 and 5 by bulky tert-butyl or α-cumyl groups with hydrochlorides of o-, m-, and p-(but-3-enyloxy) aniline in the presence of triethylamine. The obtained compounds formed by the reaction with TiCl2(OPr-i)2 complexes of titanium(IV) dichloride L2TiCl2.

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.

Substituted salicylaldehydes reacted with ethyl diazoacetate to give ethyl 1-benzofuran-3-carboxylates containing various substituents in the aromatic ring. The Diels-Alder reaction of these compounds with Danishefsky’s diene was regioselective, and it provided an effective method for the construction of the heterocyclic skeleton of hexahydrodibenzo[b,d]furan-7-one or tetrahydrodibenzo[b,d]furan-7-one. The adducts were found to undergo rearrangement to substituted 4′-hydroxybiphenyl-2-yl methyl carbonates during column chromatography on silica gel.

Triterpenoids with the following amine fragments in C3 and C28 positions were synthesized on the basis of betulinic and oleanolic acids: (3-aminopropoxy)-, 3-acetyl-(3-aminopropyl)amino-, 6-[bis(3-aminopropyl)amino]hexylamino-, and (3-aminopropyl)-4-aminophenylsulfonyl-4-phenylamino. Amide of betulonic acid with 4,4′-diaminodiphenylsulfonic substituent was shown to exhibit no antitumor effect, but to have a pronounced anti-inflammatory activity.

The review considers the main methods for the synthesis of derivatives of A-seco pentacyclic triterpenoids by means of the Baeyer-Villiger reaction, the Beckmann rearrangement, and other oxidation processes.

Plants of the genus Peucedanum attract the attention of researchers as sources of coumarins. We isolated previously from P. terebinthaceum Fischer et Turcz. of Mongolia flora the pyranocoumarin (+)-pteryxin [1]. Plants of the species Ferulopsis hystrix Bunge (P. hystrix) were characterized as sources of angular furocoumarins [2]. The species P. baicalense (Redow.) Koch is broadly distributed over Mongolia [3]. Peucedanin, imperatorin, isoimperatorin, fellopterin, deltoin, bergapten, and 8-hydroxy-5-methoxypsoralen were previously isolated from its roots [3]. We studied compounds extracted from P. baicalense collected in Baruunburen, Selenge Province, Mongolia, during budding-flowering. The concentrated EtOH extract of subterranean organs was diluted with H2O. Coumarins were extracted sequentially by hexane (1.15% yield), Et2O (0.33%), and EtOAc (2.28%). An analysis of PMR spectra of the fractions showed that the principal components of the hexane extract were diacetylene compounds, coumarins (~30%), and sterols (~12%). Extracted compounds were separated by column chromatography over silica gel. Chromatography of the hexane extract (2.4 g) isolated sequentially the diacetylene alcohol falcarinol (1) and pure linear furocoumarins isoimperatorin (2) (0.032% of raw material weight), fellopterin (3) (0.038%), and 8-(1,1-dimethylallyloxy)bergapten (4) (0.044%).

New derivatives with hydroxy, epoxy, hydroxyimino, acetoxy, lactol, methoxylactol, and indole groups in ring A and the side chain were synthesized via chemical transformations of dipterocarpol. The structure– cytotoxicity relationship was described for the dipterocarpol derivatives.

Peucedanin reacted with methylideneiminium salt generated in situ from N,N,N′,N′-tetramethylmethanediamine and acetyl chloride to give 2-(dimethylaminomethyl)oreoselone. Reactions of peucedanin with aminomethylating agents generated in situ from formaldehyde and dimethylamine, N-methylpiperazine, or N-Boc-piperazine in boiling methanol smoothly afforded the corresponding 9-aminomethyl derivatives whose hydrolysis produced 9-aminomethyl-substituted oreoselones. 2,3,9-Trisubstituted linearly fused furocoumarins were synthesized by reactions of 9-substituted oreoselone trifluoromethanesulfonates with arylboronic acids.

Derivatives of lappaconitine containing styryl, hetarylvinyl, 3-oxobutenyl, and acetyl substituents on the aromatic ring were synthesized using a Heck reaction of 5′-iodolappaconitine and various olefines.

Developed by the authors methods for the functionalization of some plant metabolites or their derivatives, viz., the eudesmane-type methylidenelactones, diterpene and morphinane alkaloids, furanolabdanoids, lupanes triterpenoids, and coumarins, using the metal complex catalysis, are reviewed.

Interaction of betulonic acid chloride with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl, and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl yielded the corresponding triterpene amides. The synthesized derivatives of betulonic acid were shown to exhibit a cytotoxic activity on models of the CEM-13, U-937, and MT-4 tumor cells. The concentration of the most active N-[3-oxo-28-norlup-20(29)-en-17-carbamoyl-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl that inhibited survival of the tumor cells by 50% (CCID50) proved to be 5.7–33.1 μM.

The review summarizes the research results and application aspects of the original series of trichlorocyclopentenones synthesized from hexachlorocyclopentadiene.

The results of ozonolysis of (R)-menth-4-en-3-one in methylene chloride, methanol, or their 1: 1 mixture in the presence of pyridine, triethylamine, or semicarbazide hydrochloride are reported. Probable schemes for the formation of ozonolysis products, including minor ones, are proposed. Nitrogen-containing organic compounds can act as reducing agents toward peroxides or catalyze their rearrangements.

The reaction of a linearly fused furocoumarin, oreoselone, with p-toluenesulfonyl chloride gave 2-tosyloreoselone which showed a high reactivity in palladium-catalyzed cross-coupling reactions with formation of a new carbon-carbon bond. 2-Tosyloreoselone reacted with terminal alkynes in the presence of Pd(PPh3)2Cl2 to give the corresponding 2-alkynylfuro[3,2-g]chromen-3-ones. 2-Aryl(hetaryl)alkynyloreoselones were obtained in high yield directly by palladium-catalyzed reaction of oreoselone with tosyl chloride and aryl(hetaryl)acetylenes. The reaction of 2-tosyloreoselone with aryl(hetaryl)boronic acids in the presence of palladium complexes with uni- and bidentate ligands, tetrabutylammonium bromide, and a base afforded 2-aryl(hetaryl)-substituted oreoselones. 2-Vinyloreoselone was synthesized from 2-tosyloreoselone and potassium trifluoro(vinyl)borate.

The synthetic and kinetic regularities of the amino-Claisen rearrangement (ACR) were studied for the transformation of 2,5-dimethyl-N-(pent-3-en-2-yl)aniline. The ACR products are formed due to the conversion of a binary π-complex formed by the reaction of N-alkenylaniline hydrochloride with hydrochloride of the solvent (2,5-dimethylaniline).

This review considers the synthetic possibilities of monoterpene ketones, such as (R)-(+)- and (S)-(-)-pulegones, (-)-menthone, (R)-(-)- and (S)-(+)-carvones, (2R,5S)-dihydrocarvone, (S)-(+)- and (R)-(-)-camphors, (R)-(-)-nopinone, (R)-(+)- and (S)-(-)-verbenones by the examples of synthesis of optically pure and enantiomerically enriched insect pheromones.

The iodination of N′-substituted (2,5-dioxopyrrolidino)[3,4-h]-6,14-endo-ethenotetrahydrothebaines with N-iodosuccinimide in trifluoroacetic acid afforded depending on the excess of the reagent either 1-iodo- or 1,2-diiodoendo-ethenotetrahydrothebaines. The Sonogashira reaction of 1-iodo-6,14-endo-ethenotetrahydrothebaines with trimethylsilylacetylene led to the formation of N′-substituted 1-(trimethylsilylethynyl)-(2,5-dioxopyrrolidino)-[3,4-h]-6,14-endo-ethenotetrahydrothebaines whose desilylation cleanly furnished the corresponding 1-ethynylendo-ethenotetrahydrothebaines. The Mannich reaction of the acetylene derivatives of tetrahydrothebaine with amines and formaldehyde catalyzed by compounds of Cu(I) provided 1-[3-(morpholin-4-yl)propynyl]-, 1-[3-(4-methylpiperazin-1-yl)propynyl]-, and 1-[3-(4-tert-butoxycarbonylpiperazin-1-yl)propynyl]-(2,5-dioxopyrrolidino)[3,4-h]-6,14-endo-ethenotetrahydrothebaines.