Amine adducts of triallylborane as highly reactive allylborating agents for Cu(I)-catalyzed allylation of chiral sulfinylimines.

The implementation of selective catalytic processes with highly active reagents is an attractive strategy that meets the modern principles of sustainable development of chemistry. In the current study, we for the first time describe the method and general principles of Cu(I)-catalyzed allylation of imines with amine adducts of allylic triorganoboranes. Triallylborane is an extremely reactive compound and cannot be used for the catalytic allylation of imines, whereas its amine adducts are ideal substrates for catalysis. The structure of the amine fragment successfully balances the safety, selectivity and stability of the allylboron reagent, allowing it to demonstrate high activity in catalytic allylation reactions, exceeding many times any known allylboranes. The obtained results are supported by quantitative kinetics data and DFT calculations. The catalytic efficacy of the system was demonstrated on model sulfinylimines (23 examples). High diastereoselectivity up to >99% was achieved, including for the gram-scale synthesis of 2-hydroxyphenyl-derivatives. Taking into account the high reactivity and unsurpassed atom-economy of amine adducts of triallylborane (AAT), they can be considered as prospective allylation reagents with Cu(I) and other appropriate metallocatalysts.

Bilateral metalloheterocyclic systems based on palladacycle and piperidine-2,4-dione pharmacophores.

The design of molecules with effective anticancer properties constructed from both dually active metal complex and organic fragments is a novel trend in medicinal chemistry. This concept suggests the impact of a drug on several biological targets or the synergistic action of both fragments as a single unit. We propose that the combination of a Pd-metallocomplex fragment and an organic unit can be an interesting model for anticancer drug discovery. The first phase in the development of such suggested molecules is the synthesis of bilateral metallosystems containing bioactive 6-substituted piperidin-2-one and a palladated N-phenylpyrazolic fragment. Both fragments were incorporated into one molecule through the fused pyrazole-piperidine-2-one unit followed by pyrazol-directed cyclopalladation of the phenyl-group with Pd(OAc)2. An effect of acceleration of the rate of the palladation by NH-lactam was observed. The synthesized hybrid palladacycles have been characterized and tested for their cytotoxic activity on three cancerous cell lines as PPh3 complexes, revealing structures with potential for further development and structural optimization.

Half-Sandwich Cyclometalated RhIII Complexes Bearing Thiolate Ligands: Biomolecular Interactions and In Vitro and In Vivo Evaluations.

A class of cyclometalated RhIII complexes [Cp*Rh(ppy)(SR)] bearing thiolate ligands, Cp* = pentamethylcyclopentadienyl, ppy = 2-phenylpyridinate, and R = pyridyl (Spy, 2), pyrimidyl (SpyN, 3), benzimidazolyl (Sbi, 4), and benzothiazolyl (Sbt, 5), were produced and identified by means of spectroscopic methods. The in vitro cytotoxicity of the RhIII compounds in three different human mortal cancerous cell lines (ovarian, SKOV3; breast, MCF-7; lung, A549) and a normal lung (MRC-5) cell line were evaluated, indicating the selectivity of these cyclometalated RhIII complexes to cancer cells. Complex 5, selected for in vivo experiment, has shown an effective inhibition of tumor growth in SKOV3 xenograft mouse model relative to control (p-values < 0.05 and < 0.01). Importantly, the outcomes of H&E (hematoxylin and eosin) staining and hematological analysis revealed negligible toxicity of 5 compared to cisplatin on a functioning of the main organs of mouse. Molecular docking, UV-vis, and emission spectroscopies (fluorescence, 3D fluorescence, synchronous) techniques were carried out on 1-5 to peruse the mechanism of the anticancer activities of these complexes. The obtained data help to manifest the binding affinity between the rhodium compounds and calf thymus DNA (CT-DNA) through the interaction by DNA minor groove and moderate binding affinity with bovine serum albumin (BSA), particularly with the cavity in the subdomain IIA. It can be concluded that the Rh-thiolate complexes are highly promising leads for the development of novel effective DNA-targeted anticancer drugs.

Construction of piperidine-2,4-dione-type azaheterocycles and their application in modern drug development and natural product synthesis.

The current review summarizes the latest achievements in the synthesis of piperidine-2,4-dione-type azaheterocycles. Two main groups traditional (carbonyl compound transformations) and novel (anionic enolate rearrangements) of complementary methods for the simple and effective preparation of structurally diverse compounds in racemic and enantiopure forms have been reported. Due to the specific structure and appropriate reactivity profiles of dione-type molecules, they are a convenient modern platform for the construction of functionalized piperidine-type systems possessing high synthetic and medicinal potential. This potential is successfully realized by the creation of highly active pharmaceutically relevant compounds and the synthesis of natural products.

Dimethylamine adducts of allylic triorganoboranes as effective reagents for Petasis-type homoallylation of primary amines with formaldehyde.

Dimethylamine adducts of triallyl-, triprenyl- and trans-cinnamyl(dipropyl)borane are effective reagents for mild homoallylation of primary amines with aqueous formaldehyde in MeOH without an inert atmosphere. A new concept is proposed for the explanation of the high stability of allylborane-amine adducts in aqueous MeOH.

Adducts of Triallylborane with Ammonia and Aliphatic Amines as Stoichiometric Allylating Agents for Aminoallylation Reaction of Carbonyl Compounds.

Triallylborane-amines adducts are effective stoichiometric allylating agents in the aminoallylation reaction of carbonyl compounds in methanol. Moreover, copper-catalyzed diastereoselective allylation of Ellman's imine was achieved with triallylborane-methylamine adduct.

Stereoselective synthesis of novel adamantane derivatives with high potency against rimantadine-resistant influenza A virus strains.

A series of (R)- and (S)-isomers of new adamantane-substituted heterocycles (1,3-oxazinan-2-one, piperidine-2,4-dione, piperidine-2-one and piperidine) with potent activity against rimantadine-resistant strains of influenza A virus were synthesized through the transformation of adamantyl-substituted N-Boc-homoallylamines 8 into piperidine-2,4-diones 11 through the cyclic bromourethanes 9 and key intermediate enol esters 10. Biological assays of the prepared compounds were performed on the rimantadine-resistant S31N mutated strains of influenza A - A/California/7/2009(H1N1)pdm09 and modern pandemic strain A/IIV-Orenburg/29-L/2016(H1N1)pdm09. The most potent compounds were both enantiomers of the enol ester 10 displaying IC50 = 7.7 µM with the 2016 Orenburg strain.