An efficient multistep synthesis of novel substituted pyrazoline derivatives linked to a dammarane scaffold was developed for the first time. Initially, ozonolysis of one of the main metabolites of Dipterocarpus alatus - 3β-hydroxy-dipterocarpol afforded natural 3β-hydroxy-hollongdione, which was subsequently subjected to a Claisen-Schmidt condensation to furnish a derivative bearing a [3-(pyridin-2-yl)-prop-2-en-1-one]-fragment at C17 and the E-configuration of the double bond was confirmed by spectral analysis. Cycloaddition of the enone intermediates with formyl or acetyl hydrazides produced a mixture of S- and R-diastereomers in a 55:45 ratio, which were successfully separated by HPLC. The most prominent distinguishing feature between the R- and S-isomers was the chemical shift of the H-17 proton, appearing at δ 2.62 and δ 2.67, respectively. Additionally, the R-isomer exhibited a more downfield resonance for the Ha-3' proton and a relatively upfield shift for the Hb-3' proton.

New 2-oxo-triterpenoids of ursane, dammarane and oleanane types were synthesised from the corresponding 3-oxo-derivatives by Willgerodte-Kindler reaction with yields of 31-42%. It was shown that their C2-oximes are formed as the equimolar mixtures of syn/anti-isomers in contrast to literature data for C3-oximes giving a single E-isomer due to the steric factors. The structures of 2-oxo- and 3-oxo-28-oxo-allobetulones as well as allobetulone 2E-oxime were confirmed by X-ray diffraction analysis. A regioisomer of natural erythrodiol - olean-12(13)-ene-2β,28-diol 19 was firstly synthesised by the reduction of methyl 2-oxo-oleanoate. The tested triterpenoids were more potent in α-glucosidase (from S. cerevisia) inhibition than acarbose (from 5 to 20 times). Erythrodiol 20 showed IC50 value of 8.35 μM, while it's regioisomer 19 was found as the most active and non-cytotoxic in terms of enzyme inhibition with an IC50 value of 14.19 μM.

The reaction of acyl isothiocyanates of 2-allyl- and 2-benzylmaleopimarimides with ethyl-, benzylhydrazine, or ethyl ester of hydrazinoacetic acid leads to the formation of maleopimarimides containing the fragment of 5-thioxo-2,5-dihydro-1H-1,2,4-triazole. The structures of the synthesized compounds were determined by 1H, 13C, 1H–13C HSQC, 1H–13C HMBC, COSY, NOESY, and 1H-15N HMBC NMR spectroscopy methods.

A series of messagenin-based chalcones has been synthesized by Claisen-Schmidt condensation and screened for in vitro alpha-glucosidase inhibitory activity. The heterocyclization of 30-(3-pyridinylidene)-messagenin led to syn/anti N-acetyl-pyrazoles in a ratio of 2 : 1 that were isolated by HPLC. Messagenin chalcones act as alpha-glucosidase inhibitors with IC50 range from 0.055 to 80.70 mu M. The lead nanomolar level alpha-glucosidase inhibitor 30-(4-hydroxymethyl-benzylidene)-messagenin 10 was studied for antihyperglycemic activity on streptozotocin-induced diabetic animal models using in vivo mechanism-based assays. In a rat model of STZ-induced T1DM, compound 10 (20 mg/kg, orally) exhibited antihyperlipidemic activity, reducing AIP (p>0.05) and CRI (p<0.05) compared to control. Compound 10 improved diabetic nephropathy, locomotor activity in rats, and reduced diabetes-related mortality.

New linear hydrazinocarbonothioyl derivatives of maleopimarimides were synthesized in high yields by the interaction of acyl isothiocyanates of 2-allyl- and 2-benzylmaleopimarimides with acetohydrazide and hydrazide of 4-methoxybenzoic acid. 1,3,4-Thiadiazole derivatives were synthesized by boiling hydrazinocarbonothioyl derivatives of maleopimarimides with a catalytic amount of concentrated H2SO4 in ethanol. The structure of the synthesized compounds was determined using 1H,13C NMR, 1H–13C HSQC, 1H–13C HMBC, COSY, NOESY, and 1H-15N HMBC spectroscopy methods.

Reaction of acyl isothiocyanates of 2-allyl- and 2-benzylmaleopimarimides with 3-carboxy- and 2,4-dinitrophenylhydrazines and hydrazides of some aromatic acids (benzoic, 4-hydroxy- and 4-methoxybenzoic, nicotinic, isonicotinic) furnished linear hydrazinocarbonothioyl derivatives of these maleopimarimides in high yields. Structure of the synthesized compounds was determined by 1H,13C, 1H–13C HSQC, 1H–13C HMBC, COSY, NOESY, and 1H–15N HMBC NMR spectroscopy methods.

The condensation of maleopimaric acid or its chloride with 2-aminothiazole or 2-aminobenzothiazole afforded new maleopimaric acid imides and amides containing thiazole or benzothiazole fragments. Maleo­pimaric acid chloride reacted with 2-aminothiazole at room in anhydrous methylene chloride at room tempera­ture to give a mixture of the corresponding N-thiazolyl amide and a maleopimaric acid derivative containing a thiazole ring in both carboxylic acid and anhydride moieties at a ratio of 7:2.

Trifluoroacetic acid-promoted Wagner-Meerwein rearrangement of betulonic acid carboxamide led to the formation of the expected 19β,28-lactam along with a new germanicane-type 3-oxo-19β-trifluoroacetoxy-18αH-oleane-28-oic acid. The structure of this triterpenoid was confirmed by 2D NMR analyses. A primary evaluation of biological potency revealed an anticancer activity with GI50 < 5 μM against leukemia, colon cancer, breast cancer, and prostate cancer cell lines, while the parent compounds were not active.

A series of new triterpenic and sitosterol derivatives containing 1,2,3,4-(tetrazol-5-yl)ethoxy and -ethoxyimine fragments at positions C-2, C-3, and C-12 have been synthesized by 1,3-dipolar cycloaddition of nitriles to sodium azide. The structure of the obtained compounds was confirmed by NMR spectroscopy, including two-dimensional correlation experiments, and mass spectrometry. It was found that such steric factors as the presence of 23,24-gem-dimethyl groups or a second cyanoethyl group at position C-2 affect the yield of the reaction product. In vitro studies have shown that methyl 2-[2-(1Н-tetrazol-5-yl)]-2,4-seco-3-norlupa-4(23),20(29)-dien-28-oate and 24-ethyl-3-[2-(1Н-tetrazol-5-yl)ethoxy]cholestan-5-ene have the highest anticancer and α-glucosidase inhibitory activities, respectively.

Cancer persists as a global challenge due to the extent to which conventional anticancer therapies pose high risks counterbalanced with their therapeutic benefit. Naturally occurring substances stand as an important safer alternative source for anticancer drug development. In the current study, a series of modified lupane and ursane derivatives was subjected to in vitro screening on the NCI-60 cancer cell line panel. Compounds 6 and 7 have been identified as highly active with GI50 values ranging from 0.03 µM to 5.9 µM (compound 6) and 0.18–1.53 µM (compound 7). Thus, these two compounds were further assessed in detail in order to identify a possible antiproliferative mechanism of action. DAPI (4′,6-diamidino-2-phenylindole) staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that both compounds induced upregulation of proapoptotic Bak and Bad genes while downregulating Bcl-XL and Bcl-2 antiapoptotic genes. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, while compound 7 showed higher in silico Bcl-XL inhibition potential as compared to the native inhibitor ATB-737, suggesting that compounds may induce apoptotic cell death through targeted antiapoptotic protein inhibition, as well.

A series of novel and previously synthesized lupane type C2-benzylidene derivatives was evaluated on alpha-glucosidase enzyme inhibition. Most of the tested compounds exhibited significantly better activity (1.8-700 times higher) than the standard drug acarbose. The structure-activity relationship indicated that the type of benzylidene moiety and C28-substituent of lupane core plays an important influence on the activity. Methyl 2-furfurylidene betulonate, m-iodo-benzylidene betulonic acid and 3-pyridinylideno-betulonic acid hydrazide have been founded as effective alpha-glucosidase inhibitors and deserve further attention.

New 2- and 3-methoxyquinopimaric-acid derivatives were synthesized by a Diels–Alder reaction of levopimaric acid and 2-methoxy-1,4-benzoquinone. The reaction rate and regioselectivity of the cycloaddition were increased significantly by using a Bmim·BF4 catalyst. Photolysis of 3-methoxyquinopimaric acid produced new scaffold derivatives. The compounds were characterized by NMR spectroscopy and elemental analysis.

A new synthetic method for 16-sulfanyl-15-oxa scaffold derivatives of quinopimaric acid was developed. The structures of all synthesized compounds were elucidated using NMR spectroscopy and elemental analysis.

Reaction of 3-oxotriterpenoids and steroids with acrylonitrile in the presence of BnEt3NCl and 30% KOH in dioxane proceeds with the formation of 2,2-biscyanoethyl derivatives substituted in the α-position to 3-oxo group. In the presence of several α-hydrogen atoms at the 3-oxo group the reaction of cyanoethylation involved the positions C 4 and C 5 , leading to 2,2,5-tricyanoethyl and 2,4-dicyanoethyl derivatives. The cyanoethylation of tetracyclic compounds occurred with the formation of monocyanoethyl derivatives with an overall increase in the yield.

New 4a-quinopimaric acid derivatives were synthesized via a Diels–Alder reaction of levopimaric acid with 2-acetyl- or 2-(methoxycarbonyl)-1,4-benzoquinone and were characterized using elemental analysis and NMR spectroscopy. Thermodynamic and activation parameters of the Diels–Alder reactions of levopimaric acid and a model diene (7-isopropyl-1,2,3,4,4a,5-hexahydronaphthalene) with 2-acetyl- or 2-(methoxycarbonyl)-1,4-benzoquinone were calculated by density-functional theory in order to explain the observed regioselective cycloaddition.

The molecular structure of 3-oxo-urs-12-en-28-oic acid anhydride is determined. Crystals of C60H90O5 compound (III) are monoclinic, space group С2, at 100 K a = 15.1308(13) Å, b = 23.5150(19) Å, c = 15.1275(12) Å, β = 108.276(2)°. Molecules in the crystal are located in a special position on axis 2.