Synthesis of N-protected staurosporinones

J Org Chem. 2007 Mar 16;72(6):2008-14. doi: 10.1021/jo062184r. Epub 2007 Feb 20.

Abstract

We report a method for the synthesis of N-protected staurosporinones, which are useful for the synthesis of indolo[2,3-a]pyrrolo[3,4-c]carbazole alkaloids and related compounds. An interaction of gramine methiodide (2) with 3-(N-benzyl)indolylacetonitrile (3) in the presence of t-BuLi, followed by a CF3COOH-catalyzed intramolecular indole-indole coupling and dehydrogenation with DDQ, produced 5-cyanoindolo[2,3-a]carbazole 6 almost quantitatively. Reduction of its cyano group followed by N-benzylation produced N-benzylaminomethylindolo[2,3-a]carbazole 8b, which was subjected to Pd(OAc)2-catalyzed direct aromatic carbonylation to give N-protected staurosporinone 9b. Treatment with AlCl3 in anisole removed N-benzyl groups to afford staurosporinone quantitatively.

MeSH terms

  • Carbazoles / chemical synthesis*
  • Catalysis
  • Indole Alkaloids / chemical synthesis*
  • Indoles
  • Ketones / chemical synthesis
  • Staurosporine / chemical synthesis*

Substances

  • Carbazoles
  • Indole Alkaloids
  • Indoles
  • Ketones
  • staurosporine aglycone
  • Staurosporine