An efficient one-pot approach to the synthesis of substituted 3-hydroxyadamantane-1-carboxylic acids has been developed. The method is based on the sequential combination of carboxylation by the Koch-Haaf reaction and oxidation in the presence of HNO3 in H2SO4 or H2SO4 center dot SO3 medium, which allows COOH and OH to be appended together into the adamantane skeleton in the same reaction vessel. Due to their diverse functionality, the obtained compounds can be used as building blocks for the synthesis of new adamantane compounds with a many field of applications.

Background The coronavirus E ion channel has previously been studied as a potential target for antiviral therapy, with several compounds found to bind to the channel. Since, these compounds have low activity, searching for effective E ion channel inhibitors of great importance.Objective This study aimed to develop a computational approach for designing ligands for the coronaviral E ion channel and identify potential inhibitors based on this approach.Methods The structure of the E-ion channel was refined using molecular dynamics, and the pore responsible for binding cage compounds was selected as the inhibitor-binding site. Potential inhibitor structures were identified using molecular docking, and their binding was confirmed using molecular dynamics simulations.Results A number of potential SARS E ion channel inhibitors have been identified, and the binding modes and possible mechanisms of action of these inhibitors have been clarified.Conclusion This study presents a computational approach that can be used to design ligands for E ion channels and identify potential inhibitors, providing valuable insights into the development of new antiviral therapies. The behavior of the E protein pentamer of SARS-CoV-2 in its native environment was investigated using Molecular Dynamics (MD), resulting in an equilibrated structure that could be used to develop new inhibitors through molecular docking. Simulation of the MD of E-channel complexes with amantadine analogues allowed for the identification of the main types of ligand-protein interactions that are responsible for the good binding of ligands within the channel's inner chamber.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry over the period 2018–2023 is presented.

Acylation reactions of CH acids have been studied, and an efficient approach to the synthesis of 1-adamantyl methyl ketone directly from 1-adamantylcarbonyl chlorides has been developed. The proposed method involves the reaction of carboxylic acid chlorides with diethyl malonate in the presence of sodium hydroxide followed by hydrolysis of intermediate keto diesters in an acidic medium and decarboxylation.

Reactions of 3-(bromomethyl)-5,7-dimethyl-2-oxaadamantan-1-ol with various nucleophiles afforded a number of new 2-oxaadamantane derivatives. The synthesized compounds may be considered as starting materials for targeted synthesis of potentially biologically active compounds.

New methods for the direct preparation of 3-hydroxy-1-adamantanecarboxylic acid and 1,3-adamantanedicarboxylic acid from 1-adamantyl halides was developed. The one-pot methods are based on the sequential combination of the Koch–Haaf and oxidation reactions in a H2SO4–HNO3 mixture. This study proposes an improved method for the preparation of 1-adamantanecarboxylic acids from 1-adamantyl halides.

A convenient approach for the synthesis of hydrocarbons by transformations of cage alcohols in the presence of 2-propanol and sulfuric acid has been proposed. Scalability, good yields and usage of readily available reagents along with synthetic convenience showed usefulness of proposed approach. This approach made it possible to obtain high preparative yields of difficult-to-reach cage hydrocarbons such as 2-methyladamantane, 2-phenyladamantane and homoadamantane. For some substrates, the potential to obtain corresponding saturated hydrocarbons or alkenylation products by varying the concentration of sulfuric acid under reaction conditions has been demonstrated

The reactions of 3-bromomethyl-5,7-dimethyl-2-oxaadamantan-1-ol in a 96% acid medium both in the presence and in the absence of nucleophiles were studied. During the reactions a number of structural transformations of the 2-oxaadamantane cage take place. The possibility of obtaining 1,2,3-trisubstituted adamantanes is also presented. The structural features of new compounds are investigated using 2D NMR spectroscopy and XRD analysis. The obtained compounds can be used in the directed synthesis of a new cage heterocycles for studying of biological activity.

1,3-Dibromoadamantane derivatives reacted with fuming nitric acid to give mixtures of products with a 2-oxaadamantane skeleton. 1,3-Diiodoadamantane analogs under similar conditions were converted only to the corresponding 1,3-dinitroxyadamantanes. A preparative procedure has been developed for the synthesis of 3-(bromomethyl)-5,7-dimethyl-2-oxaadamantan-1-ol from 1,3-dibromo-5,7-dimethyladamantane. Due to the presence of several functional groups, the synthesized compounds can be used as starting materials for obtaining derivatives exhibiting a broad spectrum of biological activity.

Reactions of 3-(bromomethyl)-5,7-dimethyl-2-oxaadamantan-1-ol with 96% sulfuric acid in the absence and in the presence of nucleophiles have been studied. These reactions involve a series of skeletal transformations and open the way to difficultly accessible 1,2,3-trisubstituted adamantanes. The structure of the synthesized compounds was studied by 2D NMR spectroscopy and X-ray analysis. The products can be used as starting materials for the synthesis of new cage heterocycles with potential biological activity.

1-Aryladamantanes were synthesized, and their transformations in fuming nitric acid were studied. The nitroxylation of the saturated framework are accompanied by the nitration of the aromatic moiety and form 3-(dinitroaryl)adamantan-1-yl nitrates. A number of new polyfunctional compounds were synthesized by the reactions of substituted 3-(dinitroaryl)adamantan-1-yl nitrates with nucleophiles in concentrated sulfuric acid. Due to their polyfunctionality, the compounds obtained can be used as starting substrates in the synthesis of substances with a wide range of biological activity and materials with a complex of valuable properties.

An efficient approach for the synthesis of amino alcohols directly from cage hydrocarbons has been developed. Multigram scalability, good yields and one-pot procedure, that utilize readily available reagents along with synthetic convenience showed its usefulness. The proposed one-pot method includes sequential reactions of cage hydrocarbon with nitric acid, further amination of intermediate nitroxy derivative with urea, followed by oxidation of previously generated amine to amino alcohol on addition of conc. H2SO4.

The reaction of 2-adamantanecarboxylic acid with an excess of chlorine in the presence of AlCl3 under heating gave 5,7-dichloro-2-adamantanecarboxylic acid. This product was sequentially introduced into the Curtius, deamination, and oxidation reactions to form 5,7-dichloro-2-adamantanone. The resulting product is a key substrate for synthesis of new substances and materials with a set of practically important properties, including both the synthesis of biologically active molecules and systems for chemiluminescent diagnostic methods.

The reaction of adamantane-2-carboxylc acid with excess chlorine in the presence of aluminum chloride on heating gave 5,7-dichloroadamantane-2-carboxylic acid which was subjected to consecutive Curtius reaction, deamination, and oxidation to obtain 5,7-dichloroadamantan-2-one. The latter is a key substrate for the synthesis of new compounds and materials with a combination of practically important properties, in particular for the preparation of biologically active compounds and systems for chemiluminescence diagnostics.

A series of new polyfunctional cage compounds were synthesized by reactions of 1-nitroxy-3-(nitroxymethyl)adamantanes with nucleophiles in 100% sulfuric acid. The replacement of nitroxy group at the bridgehead position was accompanied by hydrolysis of the nitroxymethyl fragment.

1,3-Dichloroadamantanes in fuming nitric acid were converted to mixtures of 2-oxaadamantane derivatives whose structure was determined by two-dimensional NMR methods and X-ray analysis. The resulting compounds can be used in the design of highly complex molecules as subjects for studying biological activity.

N-Adamantylated amides have been synthesized from 1-adamantyl nitrate. The reactions were carried out in the sulfuric acid media. The proposed method is usefulness for the preparation of antiviral drug tromantadine. A number of new cage aminoamides have been synthesized by reactions of N-(1-adamantyl)-2-chloroacetamide with nitrogen-containing nucleophiles. with potential biological activity.

The reaction of 4-oxahomoadamantan-5-one with hydrazine gave (3- exo ,7- endo )-7-hydroxybicyclo[3.3.1]nonane-3-carbohydrazide. The latter was reacted with benzonitrile, formamide, and p -(trifluoromethyl)benzaldehyde to obtain a number of new bicyclo[3.3.1]nonane derivatives. The structural features of the new compounds were studied using 2D NMR spectroscopy and XRD analysis. The synthesized bicyclo[3.3.1]nonanes can be used in the directed synthesis of compounds of high molecular complexity for biological activity testing.