Wilk, Wolfram; Nören-Müller, Andrea; Kaiser, Markus; Waldmann, Herbert:

Biology-Oriented Combined Solid- and Solution-Phase Synthesis of a Macroline-Like Compound Collection

In: Chemistry, Jg. 15 (2009) ; Nr. 44, S. 11976-11984
ISSN: 0947-6539
Zeitschriftenaufsatz / Fach: Biologie
Abstract:
Macrolines constitute a class of natural products that has more than 100 members and displays diverse biological activities. These compounds feature a cycloocta[b]indole scaffold that represents an interesting target structure for biology-oriented synthesis (BIOS). We have presented a solid-phase synthesis of isomerically pure cycloocta[b]indoles by employing the Pictet-Spengler reaction and the Dieckmann cyclization as key steps. The scope of this reaction sequence was investigated in more detail by using various additional diversification procedures, such as Pd-catalyzed Sonogashira or Suzuki couplings on a solid phase, thus allowing, for example, the generation of 10-substituted cycloocta[b]indole derivatives. Finally, solution-phase decoration of the cycloocta[b]indole skeleton by reduction and saponification was evaluated, thereby further extending the scope of the solid-phase synthesis.