E. V. Tret’yakova

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 pharmacological activity of amides and the ozonolysis product of maleopimaric acid

The synthesis of a new group of maleopimaric acid amides containing fragments of methyl ethers of amino acids, aliphatic amines, imidazole, and N-methylpiperazine was carried out. The ozonolysis of methylmaleopimarate occurs via the cleavage of the double bond C18(19) and the opening of an anhydrous ring with the formation of secotriacid. As a result of the screening of the anti-inflammatory and antiulcer activity of maleopimaric acid derivatives, new effective compounds such as maleopimaric acid and its methyl ether, a product of ozonolysis—diterpenic secotriacid—and maleopimaric acid amide with L-leucine were found. An important advantage of the studied compounds is the low toxicity and the presence of bidirectional activity in the absence of adverse effects on the animal.

The synthesis and anti-inflammatory activity of quinopimaric acid derivatives

Under the action of PCl5, the Beckman rearrangement of a 3: 1 mixture of Z- and E-isomeres of 18β-hydro-xydihydroquinopimaric acid resulted in 5′-caprolactam and isomeric caprolactams containing fragments of cyclic ether. Z- and E-ketoximes were separated as acetates. Using a carrageenan inflammation model, we demonstrated that the anti-inflammatory activity of quinopimaric acid derivatives was comparable with that of diclofenac.

Synthesis, structure, and acylation of dihydroquinopimaric acid hydroxy derivatives

Reduction conditions of methyl dihydroquinopimarate with sodium borohydride and lithium aluminum hydride were established. As a result of the reduction 14β-hydroxy, 17α-hydroxy, 14β,17α-dihydroxy, and 14β,17α,21α-trihydroxy derivatives were obtained. The structure of methyl esters of 14β-acetoxy- and 17α-hydroxydihydroquinopimaric acid was established by XRD and NMR methods. Mono-, di-, and triacylates were obtained from the diterpene alcohols.

Synthesis of dihydroquinopimaric acid conjugates with amino acids

Synthesis of dihydroquinopimaric acid amides and their 2β-succinyl and 2β-phthalyl derivatives containing residues of amino acids was carried out for the first time. Antiviral properties of the compounds synthesized were investigated.

Synthesis of methyl esters of betulinic acid 2-deoxy-α-glycosides and 28-oxo-19,28-epoxyoleanane

New 2-deoxy-and 2,6-dideoxy-a-L-arabinohexopyranosides of betulinic acid and 28-oxoallobetulin methyl esters were synthesized by the glycal method.

Synthesis and modifications of alkyne derivatives of dihydroquinopimaric, maleopimaric, and fumaropimaric acids

Reactions of maleopimaric and dihydroquinopimaric acid chlorides with propargyl alcohol and propargylamine afforded new terminal diterpene alkynes, and Sonogashira cross-coupling of the latter with 4-iodonitrobenzene led to the formation of arylalkynyl derivatives of Diels–Alder adducts of levopimaric acid.

Regioselective oxidation of the methyl ester of maleopimaric acid by dimethyldioxirane

Reaction of the methyl ester of maleopimaric acid and dimethyldioxirane resulted in regioselective oxidation of the bridging double bond to form the 13(15)-en-14S-hydroxy derivative.

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.