| 内容提要: |
(-)-Lemonomycin belongs to a large family of tetrahydroisoquinoline (THIQ) alkaloids, and was isolated from the fermentation broth of Streptomyces candidus in 1964. In 2000, researchers at Wyeth–Ayerst discovered that lemonomycin shows antibacterial activity against methicillin- resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF), as well as cytotoxicity to a human colon-tumor cell line (HCT-116). They also determined the structure of Lemonomycin by means of NMR spectroscopy. The compound features a tetracyclic ring system including a 3,8-diazabicyclo [3.2.1]octane core, which is typical of quinocarcin-type alkaloids.
In this paper, Kan and co-workers have achieved an efficient and enantioselective total synthesis of (-)-lemonomycin. The synthesis features a Perkin-type condensation reaction, an intramolecular Hosomi–Sakurai reaction to form a bicyclo [3.2.1] ring system, and a thermodynamically controlled Pictet–Spengler reaction to construct the tetracyclic key intermediate. The spectral data for the final product were in full agreement with those of the natural product. |