Toward the Design of Molecular Chameleons: Flexible Shielding of an Amide Bond Enhances Macrocycle Cell Permeability

被引：35

作者：

Tyagi, Mohit ^{[1
]}

Poongavanam, Vasanthanathan ^{[1
]}

Lindhagen, Marika ^{[2
]}

Pettersen, Anna ^{[2
]}

Sjoe, Peter ^{[3
]}

Schiesser, Stefan ^{[4
]}

Kihlberg, Jan ^{[1
]}

机构：

[1] Uppsala Univ, Dept Chem BMC, Box 576, SE-75123 Uppsala, Sweden

[2] AstraZeneca, Early Prod Dev, IMED Biotech Unit, Pharmaceut Sci, Gothenburg, Sweden

[3] DNDi, 15 Chemin Louis Dunant, CH-1202 Geneva, Switzerland

[4] AstraZeneca, Med Chem Resp Inflammat & Autoimmun, IMED Biotech Unit, Gothenburg, Sweden

来源：

ORGANIC LETTERS | 2018年 / 20卷 / 18期

基金：

瑞典研究理事会;

关键词：

IODOXYBENZOIC ACID IBX; MEMBRANE-PERMEABILITY; CONFORMATIONAL FLEXIBILITY; RULE; ALCOHOLS; DRUGS; OXIDATION; ALKALOIDS; 1,2-DIOLS; RECEPTOR;

D O I：

10.1021/acs.orglett.8b02447

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A series of macrocycles inspired by natural products were synthesized to investigate how side-chains may shield amide bonds and influence cell permeability. NMR spectroscopy and X-ray crystallography revealed that the phenyl group of phenylalanine, but not the side-chains of homologous or aliphatic amino acids, shields the adjacent amide bond through an intramolecular NH-pi interaction. This resulted in increased cell permeability, suggesting that NH-pi interactions may be used in the design of molecular chameleons.

引用

收藏

页码：5737 / 5742

页数：6

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