845777-57-3Relevant articles and documents
Structure-Permeability Relationship of Semipeptidic Macrocycles - Understanding and Optimizing Passive Permeability and Efflux Ratio
Le Roux, Antoine,Blaise, émilie,Boudreault, Pierre-Luc,Comeau, Christian,Doucet, Annie,Giarrusso, Marilena,Collin, Marie-Pierre,Neubauer, Thomas,K?lling, Florian,G?ller, Andreas H.,Seep, Lea,Tshitenge, Dieudonné T.,Wittwer, Matthias,Kullmann, Maximilian,Hillisch, Alexander,Mittendorf, Joachim,Marsault, Eric
, p. 6774 - 6783 (2020)
We herein report the first thorough analysis of the structure-permeability relationship of semipeptidic macrocycles. In total, 47 macrocycles were synthesized using a hybrid solid-phase/solution strategy, and then their passive and cellular permeability was assessed using the parallel artificial membrane permeability assay (PAMPA) and Caco-2 assay, respectively. The results indicate that semipeptidic macrocycles generally possess high passive permeability based on the PAMPA, yet their cellular permeability is governed by efflux, as reported in the Caco-2 assay. Structural variations led to tractable structure-permeability and structure-efflux relationships, wherein the linker length, stereoinversion, N-methylation, and peptoids site-specifically impact the permeability and efflux. Extensive nuclear magnetic resonance, molecular dynamics, and ensemble-based three-dimensional polar surface area (3D-PSA) studies showed that ensemble-based 3D-PSA is a good predictor of passive permeability.
Total synthesis of micromide: A marine natural product
Han, Jianrong,Lian, Jingtang,Tian, Xia,Zhou, Shengwei,Zhen, Xiaoli,Liu, Shouxin
, p. 7232 - 7238 (2015/02/19)
This paper describes an efficient procedure for the synthesis of micromide, a natural product that shows anti-solid-tumor activity. Our strategy involved the synthesis of N-nosyl-protected amino acids and their N-methylation with iodo-methane. The hindered oligopeptides containing N-methyl amino acids were synthesized in excellent yields and high purities.[ampi]]
The total synthesis and reassignment of stereochemistry of dragonamide
Chen, Hongliang,Feng, Yaqing,Xu, Zhengshuang,Ye, Tao
, p. 11132 - 11140 (2007/10/03)
The first total synthesis of dragonamide is reported. The synthesis has led to a reassignment of the configuration at the stereogenic centre on the alkyne-bearing fragment of the molecule.