Work

Efficient Solid-Phase Synthesis of 2-Substituted-3-Hydroxy-4(1H)-Quinolinone-7-Carboxamides with Two Diversity Positions

Year: 2007

Type: article

Abstract: A highly efficient solid-phase synthesis of 2-substituted-3-hydroxy-4(1H)-quinolinone-7-carboxamides was developed using anthranilates and bromoketones as the key synthons. Primary amines immobilized to an acid-cleavable BAL linker were acylated with 1-methyl-2-aminoterephtalate. After cleavage of the methyl ester, bromoketones were used to form resin-bound phenacyl esters. Acid-mediated cleavage and subsequent cyclization in solution afforded 3-hydroxy-4(1H)-quinolinones in high purity and yield. Highly efficient solid-phase synthesis (purity>90%, yield>80%, synthetic time=2 days using commercially available synthons) is amenable to high-throughput/combinatorial synthesis to match the high-throughput screening capability.

Source: Journal of Combinatorial Chemistry

DOI: 10.1021/cc070071v

Authors: Miroslav Soural, Viktor Krchňák

Institution: University of Notre Dame

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: Diversity oriented combinational synthesis of bisheterocyclic libraries, G3596472261, Derivatization/Functionalization of Natural Product(RMI)