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Two‐Step Synthesis of Complex Artificial Macrocyclic Compounds
Author(s) -
Madhavachary Rudrakshula,
Abdelraheem Eman M. M.,
Rossetti Arianna,
TwardaClapa Aleksandra,
Musielak Bogdan,
Kurpiewska Katarzyna,
KalinowskaTłuścik Justyna,
Holak Tad A.,
Dömling Alexander
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201704426
Subject(s) - combinatorial chemistry , druggability , chemistry , substrate (aquarium) , functional group , nanotechnology , materials science , organic chemistry , biology , ecology , biochemistry , gene , polymer
The design and synthesis of head‐to‐tail linked artificial macrocycles using the Ugi‐reaction has been developed. This synthetic approach of just two steps is unprecedented, short, efficient and works over a wide range of medium (8–11) and macrocyclic (≥12) loop sizes. The substrate scope and functional group tolerance is exceptional. Using this approach, we have synthesized 39 novel macrocycles by two or even one single synthetic operation. The properties of our macrocycles are discussed with respect to their potential to bind to biological targets that are not druggable by conventional, drug‐like compounds. As an application of these artificial macrocycles we highlight potent p53–MDM2 antagonism.