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.

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.

The oxidation of cage compounds derived from quinopimaric acid, namely γ-diketone, oxa-“bird cage,” 18-chloro-15-oxa-“bird cage,” and 16-sulfanyl-15-oxa-“bird cage,” was studied using a number of oxidating agents, including sodium percarbonate in trifluoroacetic acid at 0°C, 36

The reaction of maleopimaric acid and its acid chloride with 3-, 6-, and 8-aminoquinolines afforded quinoline containing maleopimarimides and carboxamides in high yields, respectively. Structure of the synthesized compounds was determined by 1Н, 13С, 1H–13C HSQC, 1H–13C HMBC, COSY, NOESY, and 1Н–15N HMBC NMR 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.

Substituted ureides and thioureides of maleopimaric acid (MPA) were synthesized via two methods: reaction of MPA chloride with monosubstituted ureas and thioureas and reaction of MPA chloride with KSCN and then in situ with various amines. The structures of all synthesized compounds were proven using NMR spectroscopy, X-ray crystal structure analyses, and mass spectroscopy.

The condensation of maleopimaric acid with 2-aminoethane-1-thiol, 2-aminoethan-1-ol, and 3-amino­propan-1-ol afforded in high yields new maleopimarimides containing a thiol or alcohol functionality. The structure of the synthesized compounds was confirmed by NMR and mass spectra.

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.

Three new maleopimaric acid derivatives were synthesized. The antiviral activity of 14 synthesized maleopimaric acid derivatives was tested against influenza virus A/PuertoRico/8/34 (H1N1). Several compounds were found to be potentially active etiotropic antiviral compounds.

Solvent-free protocols using microwave-assisted heating (i) or conventional heating without additives (ii) or adding K2CO3 (iii), or triturating at room temperature in the presence of K2CO3 (iv) were first used to esterify glycosaminoglycans (GAG) with maleic anhydride. High and low molecular weight hyaluronic acid (HMW and LMW HA), dermatan sulfate (Ds), heparin (HEP) and C6-oxidized HA (carboxy-HA) were used as substrates for maleation. Protocols (i)-(iii) were most effective for obtaining maleates with high DS (1.39-2.47), but had a strong degrading effect on GAG. Protocol (iv) did not have destructive effect, but was suitable for obtaining only HMW HA maleate (DS 0.71-1.15). Primary hydroxyl groups of HA and Ds showed a higher reactivity compared to the secondary ones. A specific feature of the HEP maleation was substitution of N-sulfate groups for N-maleate groups. To demonstrate the potential of the obtained maleates for thiol-ene click-chemical strategies, the reaction with L-cysteine was performed.

A Pd(acac) 2 -catalyzed reaction of allyl esters of maleopimaric and diketocage quinopimaric acid derivative with diazomethane was studied for the first time with the aim to obtain cyclopropylmethyl derivatives of the pimaric acid series as potential pharmacologically active compounds. It was shown that the reaction proceeds under mild conditions and provides the desired cyclopropylmethyl derivatives in yields of 84–98%.

New S-containing maleopimaric acid derivatives were synthesized. The structures of all synthesized compounds were elucidated using NMR spectroscopy and elemental analyses.

In vitro acetylcholinesterase (AChE) inhibition was studied using novel derivatives of (-)-cytisine derivatives N-allylcytisine-12-carbamide (A-63), cytisine-12-carbamide (A-36), N-1-adamantylcytisine-12-thiocarbamide (U-12), and 1-hydroxyquinopimaric acid (U-201). Inhibition of acetylcholinesterase with compound A-63 was described as mixed inhibition. Substances (A-36) and (U-201) acted as competitive inhibitors with Ki equal to 6.71 mM and 3.89 mM, respectively, while (U-12) behaved as an uncompetitive inhibitor with Ki at 0.07 mM. The IC50 values were estimated at 1.47, 13.73, 3.39, and 7.81 mM, respectively. According to toxicity assessment, compound A-63 was non-toxic; it did not affect A. salina viability at a concentration less than 1000 ppm, while at 1000 ppm, only 3% mortality was observed. Mortality of A. salina was less than 50% in the same concentration range for the other three compounds that allow classifying them as moderately toxic. Although tested compounds have the characteristics of weak inhibitors, they could be useful as protectors against potent organophosphates. The present research may be fundamental to the design of new substances for acetylcholinesterase inhibition.

The antimicrobial and antifungal activities of maleopimaric acid (MPA) and several of its 2- and 6-derivatives were investigated. An analysis of the results showed pronounced antimicrobial activity for 2-allylmaleopimarimide and MPA N-benzylcarboxamide against test strains of Gram-negative and Gram-positive microorganisms and antifungal activity of 2-allylmaleopimarimide against lower-fungus test strain Candida albicans. New methods for producing MPA N-benzylcarboxamide and N-hydroxymaleopimarimide that increased the yields of target products were proposed.

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.