Enantioselective Catalytic [3 + 3] Cycloaddition of Donor-Acceptor Aziridines with m-N, N-Dialkylaminophenyl Methylidenemalonates

摘要

Tetrahydroisoquinoline (THIQ) is a well-known privileged skeleton that is usually found in several biologically active natural products and synthetic drugs.1 In addition, the 1,4-disubstituted THIQ skeleton is found in natural benzophenanthidine alkaloids with a broad spectrum of biological activities, including antitumor, antiviral, antimalarial, and anti-inflammatory activities (Figure 1). For example, (+)-amurensinine is a member of the isopavine family of alkaloids, which have a tetracyclic tetrahydroisoquinoline scaffold consisting of a doubly ben-zannulated azabicyclo[3.2.2]nonane. Isopavines have valuable biological properties that can be used to treat neurological disorders such as Parkinson's disease and Alzheimer's disease. Trabectedin isolated from the sea squirt Ecteinascidia turbinata is an antitumor chemotherapy drug sold under the brand name Yondelis. Trabectedin is currently obtained by a semisynthetic process starting from safracin B, an antibiotic obtained by fermentation of the bacterium Pseudomonas fluorescens.