Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids ancistrocladinium A and B and related analogues

J Am Chem Soc. 2010 Jan 27;132(3):1151-8. doi: 10.1021/ja9097687.

Abstract

The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and B (4), which possess an unprecedented iminium-aryl axis and show high in vitro antileishmanial activities, have been synthesized via a short sequence of eight linear steps, without the need of protecting groups. Key steps were a Buchwald-Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading to the naturally predominant M-atropo-diastereomer in the case of 3, while the N,C-axis is configurationally semistable in 4. The highly convergent first access to this type of alkaloids will now facilitate the preparation of structural analogues for structure-activity relationship studies. Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3'- and N,1'-coupled analogues, ancistrocladinium C (5) and D (6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Molecular Conformation
  • Stereoisomerism

Substances

  • Isoquinolines
  • ancistrocladinium A
  • ancistrocladinium B