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.