Showing papers by "Gong Chen published in 2018"
TL;DR: A highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)–H arylation reactions, inspired by the ‘C–H’ cross-linked peptide natural products is developed.
Abstract: New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein-protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)-H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines.
142 citations
TL;DR: A Pd-catalyzed amide-directed enantioselective hydrocarbofunctionalization of unactivated alkenes with C-H nucleophiles has been developed using a chiral monodentate oxazoline (MOXin) ligand.
Abstract: A Pd-catalyzed amide-directed enantioselective hydrocarbofunctionalization of unactivated alkenes with C–H nucleophiles has been developed using a chiral monodentate oxazoline (MOXin) ligand. Various indoles react at C3 position with aminoquinoline-coupled 3-alkenamides to give γ addition products in good to excellent yield and enantioselectivity. This study represents an important advance of the development of chiral monodentate oxazoline ligands, which have been underexplored for asymmetric catalysis.
101 citations
TL;DR: In this article, a Minisci-type alkylation reaction of N-heteroarenes with alkanes under the reagent control of a hypervalent iodine oxidant PFBI-OH was reported.
Abstract: We report a highly efficient and chemoselective Minisci-type alkylation reaction of N-heteroarenes with alkanes under the reagent control of a hypervalent iodine oxidant PFBI-OH. In addition to the high reactivity, PFBI-OH demonstrated a high steric sensitivity for H abstraction of alkanes. This reaction is selective for more sterically accessible secondary C–H bonds over weaker tertiary C–H bonds. High selectivity toward penultimate methylene groups was observed for a wide range of acyclic alkanes.
86 citations
44 citations
TL;DR: A protocol for Pd-catalyzed AQ-mediated enantioselective benzylic C–H arylation of 3-arylpropanamides using Pd0 catalyst and the BINOL-phosphoramide ligand is reported.
Abstract: Palladium-catalyzed enantioselective C(sp3)–H functionalization could provide valuable reactions for organic synthesis. While significant progress has been made on monodentate directing-group-media...
42 citations
TL;DR: Mechanistic studies suggest that a sequence of 1,5-HAT of an imidate radical, iodination and cyclization might be operative, and offers a powerful means for the C(sp3)-H functionalization of alcohols.
40 citations
TL;DR: Mechanistic study suggests that the unique ability of N3• to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.
Abstract: Reversible cleavage of C(sp3)-H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C(sp3)-H bonds, such as the Cα-H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C(sp3)-H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C(sp3)-H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C-H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3• to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.
40 citations
TL;DR: A PdII -catalyzed ortho-(Csp2 )-H arylation reaction of benzaldehydes using a catalytic amount of 2-(methylsulfinyl)aniline as transient Auxiliary as transient auxiliary was developed, achieving an excellent regioselectivity for ortho-C(sp2)-H bonds over benzylic C(sp3 )- H bonds.
Abstract: A PdII -catalyzed ortho-(Csp2 )-H arylation reaction of benzaldehydes using a catalytic amount of 2-(methylsulfinyl)aniline as transient auxiliary was developed. This reaction is compatible with a broad range of benzaldehyde and aryl iodide substrates. Compared with other related reaction systems, an excellent regioselectivity for ortho-C(sp2 )-H bonds over benzylic C(sp3 )-H bonds was obtained for ortho-alkyl-benzaldehyde substrates.
19 citations
TL;DR: DFT calculations suggest that dppf forms a complex with CsCO3-, enhancing its SET reducing ability to generate an aryl radical from ArI.
18 citations
TL;DR: This synthetic strategy uses the combined methods of solution and solid phase peptide synthesis and overcomes the racemization issue for ester coupling between Ile11 and Thr8 to allow the efficient preparation of fluorescent-labeled analogs of teixobactin.
Abstract: Teixobactin is a depsipeptide natural product with potent antibiotic activity against a range of Gram-positive multi-drug resistant bacteria. Its composition features a unique L-allo-enduracididine (allo-End10), three Iles2/6/11 residues, and one D-allo-Ile5 residue. Intrigued by the potential biological impact of the stereochemistry of these residues, we synthesized teixobactin and three of its stereoisomers carrying L-End10, D-End10 or D-allo-End10. In addition, stereoisomers with D-allo-Ile shuffled to positions 2, 6 or 11 were prepared. Our synthetic strategy uses the combined methods of solution and solid phase peptide synthesis. The solution phase synthesis overcomes the racemization issue for ester coupling between Ile11 and Thr8. The solid phase synthesis improves efficiency and convergence. This method also allows the efficient preparation of fluorescent-labeled analogs of teixobactin.
13 citations
TL;DR: In this paper, a cyclic ketal-protected erythreo-β-OH-Asp 7 was synthesized from cheap chiral precursor l -diethyl tartrate in six steps without the need of column purification.
Patent•
17 Jul 2018
TL;DR: In this paper, the authors proposed a method to solve the problem of how to find the best solution for a given problem in the context of Korean language, which is called PFD (PFD).
Abstract: 포유류의 신경계 내 신경형성 또는 신경재생을 촉진하는 것에 관한 조성물, 제품 및 방법이 제공된다. 구현예는 크리조티닙 (Cri), 플루비프로펜, 리튬 클로라이드 (Li), 비타민 C (VC), 세리티닙 (Cer) 또는 피르페니돈 (PFD)을 포함하는 화합물들의 그룹의 용도에 관한 것이다. 특정 구현에서 교세포가 기능성 뉴런으로 전환된다.