Indium-Catalyzed Annulation of o-Acylanilines with Alkoxyheteroarenes: Synthesis of Heteroaryl[b]quinolines and Subsequent Transformation to Cryptolepine Derivatives

We disclose herein the first synthetic method that is capable of offering heteroaryl[b]quinolines (HA[b]Qs) with structural diversity, which include tricyclic and tetracyclic structures with (benzo)thienyl, (benzo)furanyl, and indolyl rings. The target HA[b]Q is addressed by the annulation of o-acylanilines and MeO–heteroarenes with the aid of an indium Lewis acid that effectively works to make two different types of the N–C and C–C bonds in one batch. A series of indolo[3,2-b]quinolines prepared here can be subsequently transformed to structurally unprecedented cryptolepine derivatives. Mechanistic studies showed that the N–C bond formation is followed by the C–C bond formation. The indium-catalyzed annulation reaction thus starts with the nucleophilic attack of the NH2 group of o-acylanilines to the MeO-connected carbon atom of the heteroaryl ring in an SNAr fashion, and thereby the N–C bond is formed. The resulting intermediate then cyclizes to make the C–C bond through the nucleophilic attack of the heteroaryl-ring-based carbon atom to the carbonyl carbon atom, providing the HA[b]Q after aromatizing dehydration

Mammalian-Specific Central Myelin Protein Opalin Is Redundant for Normal Myelination: Structural and Behavioral Assessments.

Opalin, a central nervous system-specific myelin protein phylogenetically unique to mammals, has been suggested to play a role in mammalian-specific myelin. To elucidate the role of Opalin in mammalian myelin, we disrupted the Opalin gene in mice and analyzed the impacts on myelination and behavior. Opalin-knockout (Opalin-/-) mice were born at a Mendelian ratio and had a normal body shape and weight. Interestingly, Opalin-/- mice had no obvious abnormalities in major myelin protein compositions, expression of oligodendrocyte lineage markers, or domain organization of myelinated axons compared with WT mice (Opalin+/+) mice. Electron microscopic observation of the optic nerves did not reveal obvious differences between Opalin+/+ and Opalin-/- mice in terms of fine structures of paranodal loops, transverse bands, and multi-lamellae of myelinated axons. Moreover, sensory reflex, circadian rhythm, and locomotor activity in the home cage, as well as depression-like behavior, in the Opalin-/- mice were indistinguishable from the Opalin+/+ mice. Nevertheless, a subtle but significant impact on exploratory activity became apparent in Opalin-/- mice exposed to a novel environment. These results suggest that Opalin is not critical for central nervous system myelination or basic sensory and motor activities under conventional breeding conditions, although it might be required for fine-tuning of exploratory behavior

Molecular simulations suggest how a branched antimicrobial peptide perturbs a bacterial membrane and enhances permeability

10.1016/j.bbamem.2012.12.015Biochimica et Biophysica Acta - Biomembranes182831112-1121BBBM