An efficient strategy for the construction of C13-oxidized cembrenolides is reported. Central to this strategy is the installation of the C13 hydroxyl group prior to cembrane macrocyclization (via formation of the C1-C2 bond), allowing access to both C13 alcohol epimers. The orientation of the C13 alcohol was found to influence the cyclization mode of the cembranolide scaffold upon furan oxidat...

The efficient cyclic aminal formation leads to the stereoselective synthesis of corresponding [2+2] macrocycles, for which dynamic covalent nature bond can be controlled under specific conditions.

The convergent synthesis of a benzofuran analog of the carbacyclic ansa compound kendomycin has been achieved by assembling three major fragments by means of epoxide opening and directed ortho lithiation. The crucial tetrahydropyran ring was formed by a highly stereoselective cationic cyclization. Analysis of all synthesized tetrahydropyran-arene compounds reveals a hindered sp(2)-sp(3) rotatio...

The hydrocarbon-stapled peptide E1(S) allosterically inhibits the kinase activity of the epidermal growth factor receptor (EGFR) by blocking a distant but essential protein-protein interaction: a coiled coil formed from the juxtamembrane segment (JM) of each member of the dimeric partnership.1 Macrocyclization is not required for activity: the analogous unstapled (but alkene-bearing) peptide is...

Prolyl oligopeptidase B from Galerina marginata (GmPOPB) has recently been discovered as a peptidase capable of breaking and forming peptide bonds to yield a cyclic peptide. Despite the relevance of prolyl oligopeptidases in human biology and disease, a kinetic analysis pinpointing rate-limiting steps for a member of this enzyme family is not available. Macrocyclase enzymes are currently exploi...

This paper describes the synthesis of four aryl amide-based macrocycles through the 1 + 1 formation of two 1,2,3-triazole units by click chemistry. Two series of aryl amide-based precursors that bear two azide or acetylene units have been prepared. Intramolecular hydrogen bonding has been utilized to induce them to adopt a U-styled conformation, which remarkably promotes the macrocyclization of...

Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodolog...

The first metalated porphyrazinediols 11 have been prepared from (L)-(+)-dimethyl tartrate via conversion into the corresponding dispoke or 2,3-dimethoxy-2,3-butanediyl protected 2,3-dihydroxymaleonitrile, Linstead macrocyclization, transmetalation, and deprotection. Their stability is very dependent on the nature of the metal ion in the cavity of the porphyrazine. Reaction of these porphyrazin...