Neurotrophic peptide aldehydes: Solid phase synthesis of fellutamide B and a simplified analog

A combination of solid phase and solution phase synthetic methods have been used to complete the total synthesis of the neurotrophic lipopeptide aldehyde fellutamide B (2). The β-hydroxy aliphatic tail was prepared by regioselective reductive opening of a cyclic sulfate, and later coupled to a solid phase resin. The synthetic compound was then examined in cytotoxicity and nerve growth factor (NGF) induction assays. A simplified analog of fellutamide B also showed activity.

Graphical abstractA total synthesis of the naturally occurring lipopeptide aldehyde fellutamide B and a simplified analog is reported. Both the natural product and the analog showed potent cytotoxicity and activity in an NGF induction assay.Figure optionsDownload full-size imageDownload as PowerPoint slide