Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium-catalyzed intramolecular C-H functionalization.

Background: Small polyfunctionalized heterocyclic compounds play important roles in the drug discovery process and in the isolation and structural identification of biological macromolecules. It is expected that ready access to diverse sets of heterocycles can not only help improving the known biological and pharmacokinetic properties of drugs, but also assist the discovery of molecules that exhibit biological effects beyond those associated with previously known macromolecules. By virtue of their inherent convergence, high productivity, their exploratory and complexity-generating power, multicomponent reactions (MCRs) are undoubtedly well suited for creating molecular diversity.

Synthesis of DEFG ring of complestatin and chloropeptin I: highly atropdiastereoselective macrocyclization by intramolecular Suzuki-Miyaura reaction.

Palladium-catalyzed intramolecular Suzuki-Miyaura reaction of linear tripeptide (23) afforded the 16-membered DEFG ring of complestatin (3) in good yield with an excellent atropdiastereoselectivity. Acidic treatment of 3 triggers a stereospecific rearrangement leading to the corresponding DEFG ring 4 of chloropeptin I.

Importance of the structure of vancomycin binding pocket in designing compounds active against vancomycin-resistant enterococci (VRE).

16-Membered meta, para-cyclophanes mimicking the vancomycin binding pocket (D-O-E ring) are designed and synthesized. The structural features of these biaryl ether containing macrocycles are: a) the deletion of the carboxyl group of vancomycin's central amino acid (amino acid D); b) the elongation of the N-terminal; c) the presence of lipidated aminoglucose at the D-ring. Cycloetherification by way of an intramolecular nucleophilic aromatic substitution reaction (S(N)Ar) is used as a key step for the construction of the macrocycle.