Dmitry S. Fadeev

Chameleonic reactivity of vicinal diazonium salt of acetylenyl-9,10-anthraquinones: synthetic application toward two heterocyclic targets.

The nature of products in the diazotization of 1-amino-2-acetylenyl-9,10-anthraquinones strongly depends on the nature of substituents at both the alkyne and at the anthraquinone core. Donor substitution (NHAr, OH) at the fourth position stabilizes the diazonium salt at C1, decelerating electrophilic cyclization at the arylethynyl substituent at C2. This effect allows the replacement of the diazonium with azide group and subsequent closure into isoxazole ring with preservation of the alkyne. In contrast, electrophilic 5-exo-dig cyclizations to condensed pyrazoles is observed for the combination of donor substituents at the aryl alkyne moiety and an OAc substituent at C4. The latter process provides a new synthetic route to 3-ethynyl-[1,9-cd]isoxazol-6-ones that are difficult to access otherwise. DFT calculations suggest that donor substituents have only a minor effect on alkyne and diazonium polarization in the reactant but provide specific transition state stabilization by stabilizing the incipient vinyl cation. This analysis provides the first computational data on electrophilic 5-exo-dig cyclization in its parent form and the nucleophile-promoted version. This cyclization is a relatively fast but endothermic process that is rendered thermodynamically feasible by the enol-keto tautomerization with concomitant aromatization in the five-membered heteroaromatic ring. Computations suggest that the importance of nucleophilic assistance in the transition state for a relatively weak nucleophile such as water is minor because the energy gain due to the Lewis base coordination to the carbocationic center is more than compensated for by the unfavorable entropic term for the bimolecular proces.

Triarylmethanols with Bulky Aryl Groups and the NOESY/EXSY Experimental Observation of a Two-Ring-Flip Mechanism for the Helicity Reversal of Molecular Propellers

Triarylmethanols - the direct precursors of persistent trityl radicals - are racemic mixtures of chiral three-bladed molecular propellers. Depending on bulkiness of aryl groups they exhibit various liabilities to interconversion, the half- life time of room temperature racemization varying in a range between 8.4 hours and 1.32 years. NOESY/EXSY experiment performed on two representative models strongly supports the two-ring flip mechanism for the configurational interchange.

Synthesis of new betulinic acid–peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity

The modification of betulinic acid derivatives bearing an ethynyl group at the C-3 position by different azidopeptides using Cu(I)-catalyzed alkyne-azide cycloaddition has been described. All obtained compounds were tested for their anti-inflammatory activity using a histamine-induced paw edema model. Betulinic acid–peptide conjugates containing histidine, alanine, tryptophan and isoleucine amino acid fragments were found to exhibit high anti-inflammatory activity, comparable to that of indomethacin. It has been shown by molecular docking that the obtained conjugates are incorporated into the binding site of the protein Keap1 Kelch-domain by their amino acid residues and form more non-covalent bonds, but have lower affinity than the initial triterpenoid core. It has been suggested that peptide moieties can modify the activity of the initial triterpenoid scaffold due to the change in the conformational and thermodynamic characteristics, which have influence on the binding of the compound to its molecular target.

Conformational Flexibility of Fused Tetracenedione Propellers Obtained from One-Pot Reductive Dimerization of Acetylenic Quinones

Reductive dimerization of acetylenic anthraquinones provides synthetic access to flexible nonplanar polyaromatics with a tetracenedione core. In solution, these nonplanar, contorted polycycles exist as equilibrating mixtures of two symmetric conformers. The fused tetracenediones are easily reduced and exhibit rich electrochemical behavior.

Dual reactivity of diazonium salts derived from 1-amino-2-ethynyl-9,10-anthraquinones

Diazotization of vicinal 1-amino-2-ethynyl-4-R-9,10-anthraquinones followed by a reaction with NaN3 gave 5-hydroxy-3-R-1H-naphtho[2,3-g]indazole-6,11-diones or 3-ethynyl-5-R-6H-anthra[1,9-cd]isoxazol-6-ones, depending on the substituents at the triply bonded C atom and in position 4 of the anthraquinone framework.

Novel Anthrathiophene-Based Small Molecules as Donor Material for Organic Photovoltaics: Synthesis and Light-Induced EPR Study

Abstract A novel anthrathiophene-based compound, 1,4-bis((5-(6,11-dioxoanthra[2,1-b]thiophene-2-yl)thien-2-yl)ethynyl)-2,5-bis(octyloxy)benzene, was synthesized and characterized. The optical absorption spectrum of the synthesized compound in film is strongly red-shifted as compared to the solution spectrum. The energies of frontier orbitals measured by cyclic voltammetry show that this compound can act as electron donor in a composite with the widely used fullerene derivative PCBM. This is confirmed by light-induced electron transfer from it to PCBM evidenced from light-induced EPR spectroscopy. The spectroscopic data suggest that anthrathiophene is a promising platform for synthesis of small-molecular electron donors for organic solar cells.

Synthesis of new combretastatin A-4 analogues and study of their anti-inflammatory activity

A new approach to the synthesis of natural combretastatin A-4 analogues based on the interaction of α-acetylenic ketones with secondary amines (diethyl amine, pyrrolidine, piperidine, morpholine) was proposed. Previously unknown analogues of combretastatin A-4 containing the β-aminovinylcarbonyl bridges were synthesized. Anti-inflammatory activity of the obtained compounds was studied on models of exudative inflammation caused by histamine or concanavalin A.

Base-catalyzed heterocyclization of 2-(R-ethynyl)benzohydroxamic acids

Sonogashira alkynylation of methyl 2-iodobenzoate with terminal acetylenes gave a series of methyl 2-(alk-1-yn-1-yl)benzoates which reacted with hydroxylamine in boiling methanol to produce five- or six-membered N-hydroxy lactams, 3-R-methylidene-2-hydroxy-2,3-dihydroisoindol-1-ones or 3-R-isoquinolin-1(2H)-ones, depending on the acetylenic substituent nature.