Synthesis and biological evaluation of novel non-racemic indole-containing allocolchicinoids.

Two novel indole-containing allocolchicinoids were prepared from naturally occurring colchicine exploiting the Curtius rearrangement and tandem Sonogashira coupling/Pd-catalyzed cyclization as the key transformations. Their cytotoxic properties, apoptosis-inducing activity, tubulin assembly inhibition and short-time cytotoxic effects were investigated. Compound 7 demonstrated the most pronounced anti-cancer activity: IC50 < 1 nM, cell cycle arrest in the G2/M phase, 25% apoptosis induction, as well as lower destructive short-time effects on HT-29 cell line in comparison with colchicine. Docking studies for prepared indole-derived allocolchicine analogues were carried out.

Stereoselective C-glycosylation reactions with arylzinc reagents.

A general, transition-metal-free, highly stereoselective cross-coupling reaction between glycosyl bromides and various arylzinc reagents leading to ß-arylated glycosides is reported. The stereoselectivity of the reaction is explained by invoking anchimeric assistance via a bicyclic intermediate. Stereochemical probes confirm the participation of the 2-pivaloyloxy group. Finally, this new method was applied to a short and efficient stereoselective synthesis of Dapagliflozin and Canagliflozin.

Direct aminoalkylation of arenes, heteroarenes, and alkenes via Ni-catalyzed Negishi cross-coupling reactions.

A room-temperature Ni-catalyzed cross-coupling of aryl, heteroaryl, and alkenyl electrophiles with aminoalkylzinc bromides, readily available from the corresponding aminoalkyl chlorides via Grignard reagents, was developed. The reaction allows a convenient one-step preparation of various aminoalkyl products, including piperidine and tropane derivatives. Such functionalized amine moieties are widely present in various biologically active molecules. Aryl, heteroaryl, and alkenyl iodides, bromides, chlorides and triflates are suitable electrophiles. A short total synthesis of two natural products, (±)-galipinine and (±)-cusparine, is also reported.

Direct aminoalkylation of arenes and hetarenes via Ni-catalyzed Negishi cross-coupling reactions.

A direct room-temperature Ni-catalyzed cross-coupling of aminoalkylzinc halides, readily available from the corresponding aminoalkyl chlorides via Grignard reagents, with aryl and hetaryl electrophiles, allows a convenient one-step preparation of aminoalkyl (het)arenes, bearing a basic tertiary nitrogen in the side chain, including piperidine and tropane derivatives. Such aminoalkylarene scaffolds are widely present in various biologically active molecules.

Synthesis of functionalized o-, m-, and p-terphenyl derivatives by consecutive cross-coupling reactions of triazene-substituted arylboronic esters.

Triazene-substituted arylboronic esters were prepared readily from the corresponding aryl magnesium derivatives and shown to function as a new class of donor-acceptor-substituted coupling reagents. The selective functionalization of these aromatic derivatives led to a wide variety of terphenyl derivatives in which the original bifunctional unit (often further substituted with another functional group) formed the central aromatic ring. The functionalized terphenyl derivatives were formed in two efficient cross-coupling steps from the triazene-substituted boronic esters: Suzuki cross-coupling with an aryl halide was followed by BF3OEt2-induced palladium-catalyzed coupling of the diazonium salt generated in situ from the triazene with an arylboronic acid.