Copper(I)‐Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α₃β‐Tetrapeptide Analogues

Abstract

A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α β-tetrapeptide framework have been successfully synthesized.

Rhodium(II)-Catalyzed Denitrogenative Annulation for the Synthesis of Substituted Tetrahydroisoquinolines

“…This strategy is inspired by our previous work on the preparation of βand β 3 -amino acids 30 and denitrogenative macrocyclization. 31 The chiral amino alkyne fragment 9 was synthesized by the conversion of Boc-D-Phg-OH using the Bestmann−Ohira reaction. 32,33 The other vital fragment was constructed by a series of functionalized modifications on the THIQ core (Scheme 3).…”

“…The 13-membered macrolactam core of the cyclocelabenzine derivative can be achieved through Cu­(I)-catalyzed macrocyclization to construct the β-amino acid analogue fragment from N -propargyl amide. This strategy is inspired by our previous work on the preparation of β- and β 3 -amino acids and denitrogenative macrocyclization . The chiral amino alkyne fragment 9 was synthesized by the conversion of Boc-D-Phg-OH using the Bestmann–Ohira reaction. , The other vital fragment was constructed by a series of functionalized modifications on the THIQ core (Scheme ).…”

A Chemoselective Polarity‐Mismatched Photocatalytic C(sp3)−C(sp2) Cross‐Coupling Enabled by Synergistic Boron Activation**

“…The authors have cited additional references within the Supporting Information. [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , ...…”

Synthesis of Macrocyclic Peptide-Diterpenoid Conjugates by a Sequential Arylation/Peptide Coupling/Click Macrocyclization Procedure

“…1 H and 13 C NMR spectra of the compound 9a (yield 76 %) are consistent with previous report. [38,39] The compound 9d (yield 90 %) was used for the next step without purification.…”