Total Synthesis of (+)-Lepadin B: Stereoselective Synthesis of Nonracemic Polysubstituted Hydroquinolines Using an RC-ROM Process

摘要

Lepadins are members of a growing family of natural products possessing a cis-fused decahydroquinoline subunit in which five stereogenic centers are included. Lepadin A (1) and B (2), which were isolated from the tunicate of Clavelina lepadiformis, have been shown to exhibit significant in vitro cytotoxicity against several human cancer cell lines. In addition, Tsuneki et al. recently identified lepadin B as a potent blocker of neuronal nicotinic acetylcholine receptors (nAChR's) α4β2 and α7. As nAChR's have been implicated in several neurological disorders including nicotinic addiction, epilepsy, and Parkinson's and Alzheimer's diseases, lepadin B could represent a new lead for the development of nicotinic-based therapies. These structural and biological features motivated research groups worldwide to address the synthetic question of lepadin B, culminating to date in three asymmetric total syntheses based on enzymatic and chiron approaches.