RESUMO
Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at ß2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and (+)-Cocculidine, both found to be potent antagonists of the ß2-containing nAChRs.
Assuntos
Alcaloides , Erythrina , Indolizinas , Receptores Nicotínicos , Alcaloides/farmacologia , Descoberta de DrogasRESUMO
A nickel-catalyzed reductive dimerization of bromocyclobutenes to produce unusual and unprecedented cyclobutene dimers was developed. In a stereoconvergent procedure, various bromocyclobutenes were readily dimerized in good yields, with good diastereoselectivities and broad functional group tolerance. Notably, the presence of a carbonyl group in the starting material appears to dictate diastereoselectivity.
RESUMO
We describe the single-step formation of complex tetracyclic fused scaffolds enabled by (3 + 2) cycloaddition of azomethine ylides. Various indoles, N-protecting groups, and amino acids are well tolerated. The products are obtained in a catalyst-free manner with moderate to excellent yield and high diastereoselectivity. Representing a new scaffold that is not yet found in nature, the construction of pyrrolidine-fused cyclohepta-, azepino-, or oxepinoindoles could be found valuable in the synthesis of new pseudo-natural products.