Biology-oriented combined solid- and solution-phase synthesis of a macroline-like compound collection.
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.
Wilk
Wolfram
W
Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Nören-Müller
Andrea
A
Kaiser
Markus
M
Waldmann
Herbert
H
D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D000078183:Oxindoles; D012996:Solutions; D013237:Stereoisomerism; D013379:Substrate Specificity
D026121:Indole Alkaloids; D007211:Indoles; D000078183:Oxindoles; D012996:Solutions; C512190:macroline; C030374:indole