Rapid Combinatorial Access to Macrocyclic Ansapeptoids and Ansapeptides with Natural-Product-like Core Structures

Abstract

14-Membered ansa-cyclopeptide alkaloids are among the most abundant natural macrocycles and thus valuable templates for diversity-oriented synthesis with biological relevance. A rapid synthesis of the core structure is conceivable by a combination of an Ugi four-component reaction with bifunctional building blocks to form the dipeptoid part, followed by a suitable macrocyclization reaction. The latter step is crucial, and an uncommon macroetherification gave the best results. The use of ammonium salts allows direct access to peptides instead of peptoids. Depending on the substitution pattern, some cyclopeptoids show planar chirality despite free rotation of the phenylene group.

alkaloids - cyclopeptides - macrocycles - ansa compounds - multicomponent reaction - planar chirality - natural product analogues

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Broad signals in the ¹H NMR spectrum and the presence of additional signals in the ¹³C NMR spectrum suggest coexisting conformers. Spectral data refer to major isomer.

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