E. V. Suslov

Competing Michael and Knoevenagel reactions of terpenoids with malononitrile on basic Cs-beta zeolite

Abstract Basic cesium-beta (Cs-beta) zeolite has been synthesized. It proved to be an effective catalyst in reactions of a number of α,β-unsaturated carbonyl compounds with malononitrile. It is shown that the process is either the Michael or Knoevenagel reaction, or tandem transformations generally initiated by the Michael reaction, which depends on steric hindrance at the carbonyl group and the β-position of the carboncarbon (CC) double bond adjacent to the carbonyl group.

Synthesis and anxiolytic activity of 2-aminoadamantane derivatives containing monoterpene fragments

Two new amines were synthesized from 2-aminoadamantane and the available monoterpenoid aldehydes citral and (–)-myrtenal. It was established that the synthesized amines possessed anxiolytic activity.

Synthesis and analgesic activity of new compounds combining azaadamantane and monoterpene moieties

Synthesis of new compounds that combine the diazaadamantane and monoterpenoid moieties was carried out based on the reaction between dimethylbispidinone and monoterpene-derived aldehydes. Investigation of the analgesic activity of the obtained products revealed that compound 5a synthesized from (−)-myrtenal had a higher efficacy compared with the reference drug, diclofenac sodium, in the acetic acid-induced writhing and hot plate tests. Compound 5a exhibits a low acute toxicity and does not cause damage to the gastric mucosa, and its analgesic effect is, at least partially, mediated by the cannabinoid system involving CB1 receptors.

Reactions of Some Terpenes and Their Derivatives with Acylating Agents in the Presence of Aluminosilicate Catalysts

Reactions of camphene, α-fenchene, limonene, caryophyllene, α- and β-pinenes, verbenol, walterol, and verbenone with acylating agents in the presence of clay K-10 and wide-porous β-zeolite were studied. Presumable schemes and rules of the occurring processes were considered.

Catalytic Asymmetric Addition of Diethylzinc to Benzaldehyde Using α- Pinene-Derived Ligands

The amines obtained from � -pinene and containing a phenol or pyridine fragment can be used as ligands in the asymmetric addition of diethylzinc to aromatic aldehydes; the enantiomeric excess (ee) was up to 80%. The enantioselectivity of the reaction is not very sensitive to the nature of substituents in the aromatic ring of aldehydes.

Reactions of some terpenoids with CH-acids in the presence of Cs-β zeolite

Reactions of some α,β-unsaturated ketones from terpenoid series with CH-acids in the presence of Cs-β zeolite were studied under various conditions. The variation of reaction conditions (heating, ultrasonic irradiation) strongly affected the reaction products ratio, and the effect was singular in each case and gave different results.

Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.

Effect of 2-aminoadamantane derivatives on behavior of mice in a modified light/dark test.

The effects of two derivatives of 2-aminoadamantane, enantiomers J447H and J579, on the behavior of male and female C57Bl/6J mice were studied using a modified light/dark test. The substances differed by their effects on the behavior of male mice. J579 reduced the number of rearings. J447H in a dose of 1 mg/kg affected more parameters: it reduced exploratory activity 1 h after administration and stimulated exploratory and motor activity in 2 h. In female mice, J447H significantly reduced the number of peepings into holes in 2 h after administration. The results indicate that further analysis of the effects of J579 and especially J447H is required.

Synthesis and analgesic activity of amines combining diazaadamantane and monoterpene fragments

BACKGROUND It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity. OBJECTIVE In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity. METHODS Their structures were confirmed by various analytical methods, such as 1H and 13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test. RESULTS Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg. CONCLUSION Structure-activity relationships indicated that the most active compound combines fragments of (-)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.

Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

The antiviral activity of several diaza-adamantanes containing monoterpenoid moieties against a rimantadine-resistant strain of the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. Hetero-adamantanes containing monoterpene moieties at the aminal position of the heterocycle were found to exhibit lower activity compared to compounds with a diaza-adamantane fragment and a monoterpene moiety linked via an amino group at the 6-position of the hetero-adamantane ring. The highest selectivity index (a ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration) out of 30 was observed for compound 8d, which contains a citronellal monoterpenoid moiety. Diaza-adamantane 8d was superior to its adamantane-containing analog 5 both in its anti-influenza activity and selectivity. Furthermore, 8d has more balanced physicochemical properties than 5, making the former a more promising drug candidate. Modelling these compounds against an influenza virus M2 ion channel predicted plausible binding modes to both the wild-type and the mutant (S31N).