C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• analogs. Keywords: cyclopamine; C–H-functionalization; hedgehog signaling pathway; natural products; steroidal alkaloids; Introduction The isolation of cyclopamine (1, Figure 1) nearly 50 years ago followed by the determination of its biological target and pharmacological profile has drawn considerable

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity. Keywords: cyclopamine; hedgehog signaling pathway; natural products; steroidal

• alkaloids; structure–activity relationship; Introduction Hedgehog signaling is involved in embryonic development and plays an important role in the maintenance of stem cells, tissue repair and regeneration in adult organisms [1][2][3][4]. The erroneous activation of hedgehog signaling is tightly associated