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Biology‐Oriented Combined Solid‐ and Solution‐Phase Synthesis of a Macroline‐Like Compound Collection
Author(s) -
Wilk Wolfram,
NörenMüller Andrea,
Kaiser Markus,
Waldmann Herbert
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901797
Subject(s) - indole test , solid phase synthesis , combinatorial chemistry , chemistry , saponification , sonogashira coupling , phase (matter) , reagent , stereochemistry , organic chemistry , catalysis , peptide , palladium , biochemistry
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.