Exploitation of the Ugi–Joullié Reaction in the Synthesis of Libraries of Drug-Like Bicyclic Hydantoins

James D. Firth; Rong Zhang; Rémy Morgentin; Rachel Guilleux; Tuomo Kalliokoski; Stuart Warriner; Richard Foster; Stephen P. Marsden; Adam Nelson

doi:10.1055/s-0034-1378704

Synthesis, Inhaltsverzeichnis

Synthesis 2015; 47(16): 2391-2406
DOI: 10.1055/s-0034-1378704

special topic

Exploitation of the Ugi–Joullié Reaction in the Synthesis of Libraries of Drug-Like Bicyclic Hydantoins

James D. Firth

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

,

Rong Zhang

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

,

Rémy Morgentin

^bEdelris, 115 Avenue Lacassagne, 69003 Lyon, France

,

Rachel Guilleux

^bEdelris, 115 Avenue Lacassagne, 69003 Lyon, France

,

Tuomo Kalliokoski

^cLead Discovery Center GmbH, Otto-Hahn-Straße 15, 44227 Dortmund, Germany

,

Stuart Warriner

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

^dAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK eMail: a.s.nelson@leeds.ac.uk

,

Richard Foster

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

^dAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK eMail: a.s.nelson@leeds.ac.uk

,

Stephen P. Marsden

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

,

Adam Nelson*

^aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK

^dAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK eMail: a.s.nelson@leeds.ac.uk

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Abstract

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Abstract

A general and efficient method for the synthesis of drug-like fused bicyclic hydantoins is reported. An Ugi–Joullié reaction/cyclisation sequence was exploited as the key complexity-generating process in which trifluoroacetic acid was employed as synthetic equivalent for chloroformic acid. Exemplar diversification of the bicyclic scaffolds was performed to enable subsequent translation to the synthesis of large small molecule libraries, leading to the production of >1000 compounds for addition to the screening collection of the European Lead Factory.

Key words

multicomponent reactions - scaffolds - libraries - Ugi reaction - hydantoin

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Referenzen

References

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