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Synthesis and Analysis of Natural‐Product‐Like Macrocycles by Tandem Oxidation/Oxa‐Conjugate Addition Reactions
Author(s) -
Lee Hyunji,
Sylvester Kayla,
Derbyshire Emily R.,
Hong Jiyong
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201900620
Subject(s) - chemical space , natural product , tandem , conjugate , combinatorial chemistry , drug discovery , tetrahydropyran , chemistry , allylic rearrangement , space (punctuation) , molecule , nanotechnology , computer science , stereochemistry , organic chemistry , ring (chemistry) , materials science , catalysis , mathematics , biochemistry , mathematical analysis , composite material , operating system
As traditional small‐molecule drug discovery programs focus on a relatively narrow range of chemical space, most human proteins are viewed as unreachable targets. Consequently, there is a strong interest in expanding the chemical space in drug discovery beyond traditional small molecules. Here, a strategy for the preparation of a broad natural‐product‐like macrocyclic library by using the tandem allylic oxidation/oxa‐conjugate addition and macrocyclization reactions is reported. Cheminformatic analyses demonstrate that this tetrahydropyran‐containing macrocyclic library shows a significant overlap with natural products in the chemical space. This approach can be used for designing libraries that may probe more deeply into natural‐product‐like space.