The solid-phase synthesis of a cyclic peptide containing the 21-residue epitope found in the A-B loop of the Cepsilon3 domain of human immunoglobulin E has been carried out. The key macrocyclization step to form the 65-membered ring is achieved in approximately 15% yield via an "on-resin" Sonogashira coupling reaction which concomitantly installs a diphenylacetylene amino acid conformational co...

The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuk...

In this article, we describe further studies toward the originally proposed structure of diazonamide A (1). After confronting a number of failures in synthesizing the heterocyclic core of that structure, success was finally realized through the development of a novel hetero-pinacol-based macrocyclization cascade sequence. Subsequent elaboration led to an advanced compound bearing both of the 12...

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There is an ever-increasing interest in synthetic methods that not only enable peptide macrocyclization, but also facilitate downstream application of the synthesized molecules. We have found that aziridine amides are stereoelectronically attenuated in a macrocyclic environment such that non-specific interactions with biological nucleophiles are reduced or even shut down. The electrophilic reac...

The facile synthesis of the cage molecule (C110H56Br2) via a remarkable three-fold homo-coupling macrocyclization reaction using continuous flow methodology is reported. Synthesis via continuous flow chemistry improves the residence time, safety, and environmental profile of this synthetically challenging reaction. Further, the new cage possesses halogen atoms at its apex that serve to expand t...