Sulfone-Mediated Total Synthesis of (±)-Lepadiformine

✍ Scribed by John J. Caldwell; Donald Craig

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 127 KB
• Volume: 46
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200604670

✦ Synopsis

À)-Lepadiformine ( 1) is a decahydro-1H-pyrrolo[1,2-j]quinoline isolated in 1994 by Biard et al. from the tunicate Clavelina lepadiformis. [1] Lepadiformine has moderate in vitro cytotoxic activity towards various tumor cell lines, including nonsmall-cell lung carcinoma (NSCLC-N6), and is also a cardiac-K + -channel blocker. [2] Lepadiformine is related both biologically and structurally to the marine alkaloid (À)-fasicularin (2) [3] and the cylindricines 3. [4] In the late 1990s, the research groups of Weinreb [5] and Pearson [6] showed independently through unambiguous total syntheses that 1 must have the 7aR,11aS relative configuration corresponding to trans fusion of the carbocycle to the octahydroindolizine substructure. The relative configuration of all stereocenters in structure 1 was proved by the first total synthesis of the racemic natural product, which was completed by Kibayashi and co-workers in late 1999. [7a] The same research group established the absolute configuration of 1 in 2002.