I. E. Smirnova

Synthesis, structure, and pharmacological activity of (7r,8s)-epoxy-(13r,17r)-trioxolane abietic acid

The synthesis of (7R,8S)-epoxy-(13R,17R)-trioxolane abietic acid was carried out and its structure was established by X-ray diffraction. The antineoplastic activity and the ability to induce apoptosis that were predicted by a PASS computer system, correlate well with the experimentally found cytotoxic activity towards the MeWo malignant cell line. The results of tests on animals showed that abietic acid and its (7R,8S)-epoxy-(13R,17R)-trioxolane derivative have anti-inflammatory and antiulcer activities in the absence of side effects.

Synthesis and anticancer activity of aminopropoxytriterpenoids

Triterpenoids with aminopropoxy groups in C-28 or C-3 and C-28 positions were synthesized from betulin, erythrodiol, uvaol, oleantriol and betulinic acid N-methylpiperazinylamide by cyanoethylation and the following catalytic hydrogenolysis. Computational estimating activity spectra of the designed compounds pointed out on their probable antineoplastic and proapoptotic activities. Their in vitro cytotoxic activity was evaluated at the National Cancer Institute, USA. Aminopropoxy derivatives of betulin, erythrodiol and oleantriol demonstrated the highest cytotoxic activity toward the most of 60 used tumor cell lines. Bisaminopropoxyerythrodiol revealed in vivo significant antineoplastic activity toward five mouse solid transplantable tumors. The results of in silico investigations and the efficacy of compounds in a broad panel of cell lines in vitro and the activity of bisaminopropoxyerythrodiol on the in vivo tumor models strongly suggest aminopropoxytriterpenoids as promising compounds for further investigation as anticancer agents.Graphical Abstract

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.

Ozonolysis of cyclomusalenone and its derivatives

Joint ozonolysis of cyclomusalenone O-methylketoxime and methyltrifluoromethylketone formed stereoisomeric triterpene 1,2,4-trioxolanes and N-methoxylactam. The structure of (24S)-24-methyl-29nor-cycloart-3,25-dione, which was obtained from ozonolysis of cyclomusalenone, was established by an x-ray crystal structure analysis.

Synthesis and evaluation of 2,3-indolotriterpenoids as new α-glucosidase inhibitors

A series of ring-A fused heterocycles of lupane, oleanane, ursane and dammarane triterpenoids were synthesized and evaluated for their inhibitory activity against α-glucosidase. An influence of the different types of triterpenoids with indole and pyrazine cycles on the activity was revealed. Among them, 2,3-indolo-lup-20(29)-en-28-oic acid with an IC50 of 1.8 µM was the most active compound being 221-fold more active than the market drug acarbose. In the most cases, the replacement of the indole by the pyrazine fragment provided the decreasing of activity (except dammarane type pyrazine derivative).Graphical Abstract

Synthesis and Cytotoxicity of Derivatives of Dipterocarpol, a Metabolite of Dipterocarpus alatus

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.

Ozonolysis of dipterocarpol and its derivatives

Oxidation of dipterocarpol and its derivatives with ozone gave compounds containing lactone, lactol, alkoxytetrahydrofuran, aldehyde, and methyl ketone fragments in the side chain, as well as 1,2,4-trioxolane fragment in the A ring. The molecular and crystalline structures of dipterocarpol were determined by X-ray analysis.

Synthesis of heterocyclic derivatives of dihydroquinopimaric acid

Heterocyclic derivatives of dihydroquinopimaric acid were synthesized, in which indole, pyrazole, or pyrimidine ring is fused to the E ring of the acid.

Regioselective bromination of quinopimaric acid derivatives

Regioselective bromination of 14β-hydroxydihydroquinopimaric acid methyl ester in acetic acid and methanol gave the corresponding 16S-bromo-, 19R-bromo-, and 16S,19R-dibromo-14β,20-epoxy derivatives whose structure was determined by X-ray analysis and NMR spectroscopy. The reactions of 16S-bromo ketones with thiourea afforded 2,1,3-thiadiazoles fused to diterpene fragment.

Synthesis of new cyanoethyl derivatives from 3-oxotriterpenoids

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 C4 and C5, 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.