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A chemical reagent to access methyl sulfones has been developed. Its reaction with various bis-nucleophiles leads to the rapid formation of previously unknown heteroaromatic methyl sulfones. Analogous strategy can also be used to construct alkyl-, CHF 2 -, CF 3 - and even bicyclo[1.1.1]pentane-containing derivatives. These compounds have been demonstrated to have a high potential for use in medicinal chemistry and coordination chemistry., Competing Interests: Competing interests: The authors declare the following competing interests: Y. P., V. R., S. B., A. B., Y. V. D., A. A. T., I. V. S., and P. K. M. are employees of a chemical supplier Enamine. The remaining authors declare no competing interests., (© 2025. The Author(s).)

The chemoselectivity of halo(het)arene sulfonyl halide aminations is studied thoroughly under parallel synthesis conditions, and the scope and limitations of the method are established. It is shown that S N Ar-reactive sulfonyl halides typically undergo sulfonamide synthesis during the first step; the second amination is also possible provided that the S N Ar-active center is sufficiently reactive. On the contrary, sulfonyl fluorides bearing an arylating moiety undergo selective transformation at the latter reactive center under proper control. Further sulfur-fluoride exchange (SuFEx) is also possible, which can be especially valuable for some sulfonyl halide classes. The developed two-step parallel double amination protocol provides access to a 6.67-billion compound synthetically tractable REAL-type chemical space (76% expected synthesis success rate).

The unprovoked Russian invasion has created considerable challenges for Ukrainian science. In this article, we discuss actions needed to support and rebuild Ukrainian science and educational systems. The proposed actions take into account past Ukrainian scientific achievements including developments in organic chemistry.

Ukrainian companies occupy an important niche in the global drug discovery process; however, before the Russian invasion, the role of Ukraine was not obvious. The biggest Ukrainian fine chemical supplier, Enamine Ltd, had to stop operation for more than a month, which significantly affected various early-stage drug discovery projects. The role of Enamine in drug discovery and the company's past and future in the context of the Russian invasion are described in this Viewpoint., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

A convenient "green" stereoretentive approach to sp 3 -enriched secondary sulfonamides bearing an asymmetric center at the α position to the sulfur atom is described. The method relies on the electrophilic amination of the corresponding stereochemically pure sulfinates with N -alkylhydroxylamine sulfonic acids (in turn easily prepared from N -alkylhydroxylamine and HSO 3 Cl). It is shown that the efficiency of the approach is governed mainly by steric factors; its tolerance to several functional groups (e.g., ether, phthalimide, or N -Boc carbamate) is also demonstrated.

A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied in vivo ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Structural restriction of the sulfonamide bond was used to design sultams with abnormal geometric parameters. Based on analysis of tertiary aliphatic sulfonamides published in the Cambridge crystallographic database, Paquette's sultams (i.e., bridged bicyclic sultams with a bridgehead nitrogen atom) were outlined, and a number of these compounds (including the novel smallest representative, 2-thia-1-azabicyclo[2.1.1]hexane 2,2-dioxide) were synthesized by cyclization of the corresponding amino sulfonyl fluorides. A series of tertiary aliphatic sulfonamides was studied by crystallographic and quantum chemical methods. It was found that the s-character of the nitrogen lone pair is the most important factor defining properties of the S-N bond. Thus, going from the sp 3 -hybrid lone pair in common sulfonamides to the sp-like lone pair in the smallest Paquette's sultam resulted in an increase in S-N bond length by ca. 0.06 Å. The strain energy of ca. 30 kcal/mol was predicted for the latter compound, which was higher than for any existing sulfonamides studied.

Diverse trifluoromethyl-substituted compounds were synthesized by deoxofluorination of cinnamic and (hetero)aromatic carboxylic acids with sulfur tetrafluoride. The obtained products were used as starting materials in the preparation of novel fluorinated amino acids, anilines, and aliphatic amines - valuable building blocks for medicinal chemistry and agrochemistry.

Two novel solid reagents-1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives-for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pK a , Log P, microsomal stability, and reactivity towards typical electrophiles). Similar to other organosulfur(VI) derivatives with S=N bonds, these compounds can be considered as promising bioisosteres of amides, ureas, or sulfonamides., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Despite intense interest in expanding chemical space, libraries containing hundreds-of-millions to billions of diverse molecules have remained inaccessible. Here we investigate structure-based docking of 170 million make-on-demand compounds from 130 well-characterized reactions. The resulting library is diverse, representing over 10.7 million scaffolds that are otherwise unavailable. For each compound in the library, docking against AmpC β-lactamase (AmpC) and the D 4 dopamine receptor were simulated. From the top-ranking molecules, 44 and 549 compounds were synthesized and tested for interactions with AmpC and the D 4 dopamine receptor, respectively. We found a phenolate inhibitor of AmpC, which revealed a group of inhibitors without known precedent. This molecule was optimized to 77 nM, which places it among the most potent non-covalent AmpC inhibitors known. Crystal structures of this and other AmpC inhibitors confirmed the docking predictions. Against the D 4 dopamine receptor, hit rates fell almost monotonically with docking score, and a hit-rate versus score curve predicted that the library contained 453,000 ligands for the D 4 dopamine receptor. Of 81 new chemotypes discovered, 30 showed submicromolar activity, including a 180-pM subtype-selective agonist of the D 4 dopamine receptor.

A practical synthesis of 2,4-methanopyrrolidines was elaborated. The key synthetic step was an intramolecular photochemical [2 + 2]-cycloaddition of an acrylic acid derivative in flow. In spite of a higher molecular weight, 2,4-methanopyrrolidines were shown to have higher solubility in water and lower lipophilicity than pyrrolidines, important characteristics of bioactive molecules in drug design.

The results of the study on reactions of halogenoximes bearing (protected) functional groups or fluorinated substituents with various phosphorus-containing dipolarophiles are described. To control the regioselectivity of the reaction, vinylphosphonates bearing a leaving group (i.e. bromine or dialkylamino group) in the α or β position were used; 3,5- and 3,4-disubstituted isoxazoles were obtained in 47-80% and 63-75% yields, respectively. The reaction was also effective for the parent vinyl phosphonate and cyanophosphonate; in this case, the corresponding isoxazoline- and 1,2,4-oxadiazole-derived phosphonates were isolated in 55-69% and 34-73% yields, respectively. The utility of the products obtained was demonstrated by the preparation of direct conformationally restricted analogues of phosphohistidine.

Difluorocyclopropane-containing building blocks for drug discovery were synthesized from the functionalized alkenes and TMSCF 3 /NaI. Novel fluorinated acids, amines, amino acids, alcohols, ketones and sulfonyl chlorides were obtained., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A one-step synthesis of functionalized 3-azabicyclo[3.2.0]heptanes by [2+2]-photochemical intermolecular cycloaddition of N-benzylmaleimide to alkenes was elaborated. The obtained compounds were easily transformed into the bi- and tricyclic analogues of piperidine, morpholine, piperazine, and GABA, which are advanced building blocks for drug discovery.

Cyclic saturated aminosulfonyl fluorides were synthesized as their HCl salts. The compounds were found to be stable upon storage and could be used for the protecting-group-free synthesis of sulfonamides. In the presence of the -SO 2 F group, the nitrogen atom could be modified by means of acylation, arylation, or reductive amination to give products that have high potential for the synthesis of bioactive compounds., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps-synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Facile synthesis of 5-fluoropyrazoles by direct fluorination of pyrazoles with N-fluorobenzenesulfonimide (NFSI) was elaborated. This approach was used to prepare the unsubstituted 5-fluoro-1 H-pyrazole, the known fungicide Penflufen, and many functionalized 5-fluoropyrazoles: building blocks for medicinal chemistry and agrochemistry.