28 Dec 02:22
by Zhao Wu, Summer D. Laffoon, Trang T. Nguyen, Jacob D. McAlpin, Kami L. Hull
A general asymmetric route for the one-step synthesis of chiral β-branched amides is reported through the highly enantioselective isomerization of allylamines, followed by enamine exchange, and subsequent oxidation. The enamine exchange allows for a rapid and modular synthesis of various amides, including challenging β-diaryl and β-cyclic.
A domino process: A RhI/chiral BINAP catalysis is reported for the one-step modular synthesis of chiral β-branched amides with various amine nucleophiles. β-dialkyl, β-diaryl, and β-alkylaryl stereocenters are established under identical conditions with excellent enantio- and diastereoselectivity in a ligand-controlled manner.
29 Nov 01:20
by Yiping Cao, Shugang Li, Yapeng Fang, Katsuyoshi Nishinari and Glyn O. Phillips
23 Nov 17:22
by Stefan J. McCarver, Jennifer X. Qiao, Joseph Carpenter, Robert M. Borzilleri, Michael A. Poss, Martin D. Eastgate, Michael Miller, David W. C. MacMillan
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 photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.
Oh, take me back to the start: A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors was developed. This photoredox method enables the efficient synthesis of cyclic peptides containing γ-amino acids, is tolerant of functionalities present in natural amino acids. Linear precursors ranging from 3 to 15 amino acids can be effectively cyclized by using this method.
23 Nov 17:20
by Stephanie R. McCabe, Peter Wipf
The first enantioselective total synthesis of (−)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2(S-TBPTTL)4, and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)-1 was completed by a late-stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.
Ringing the changes: An enantioselective total synthesis of (−)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the use of unsubstituted allene in a transition-metal-mediated enantioselective cyclopropanation to deliver a methylenecyclopropane (MCP). This transformation gives direct and atom-economical access to MCPs and could be further expanded for the synthesis of diverse “spring-loaded” reagents in organic synthesis.