Synthesis and Analysis of Natural-Product-Like Macrocycles by Tandem Oxidation/Oxa-Conjugate Addition Reactions.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lee, H; Sylvester, K; Derbyshire, ER; Hong, J

Published Date

  • May 2019

Published In

Volume / Issue

  • 25 / 26

Start / End Page

  • 6500 - 6504

PubMed ID

  • 30912197

Electronic International Standard Serial Number (EISSN)

  • 1521-3765

International Standard Serial Number (ISSN)

  • 0947-6539

Digital Object Identifier (DOI)

  • 10.1002/chem.201900620


  • eng