Natural products comprise a diverse array of molecules, many of which are biologically active. Most natural products are derived from combinations of polyketides, peptides, sugars, and fatty-acid building blocks. Peptidic macrocycles have attracted attention as potential therapeutics possessing cell permeability, stability, and easy-to-control variability. Here, we show that enzymes from the pa...

A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this phot...

Cesium alkanoates (chiefly the propionate) have been investigated for their solubility, nucleophilic reactivity, and degree of ion pairing in dimethylformamide (DMF) and, in some cases, dimethyl sulfoxide (DMSO) solutions. 133Cs NMR has been used to establish the degree of ion pairing. From the data obtained it is concluded that the cesium ion is virtually completely solvated and that the carbo...

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...