Synthesis 2015; 47(16): 2391-2406
DOI: 10.1055/s-0034-1378704
special topic
© Georg Thieme Verlag Stuttgart · New York

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

James D. Firtha, Rong Zhanga, Rémy Morgentinb, Rachel Guilleuxb, Tuomo Kalliokoskic, Stuart Warrinera, d, Richard Fostera, d, Stephen P. Marsdena, Adam Nelson*a, d
  • aSchool of Chemistry, University of Leeds, Leeds LS2 9JT, UK
  • bEdelris, 115 Avenue Lacassagne, 69003 Lyon, France
  • cLead Discovery Center GmbH, Otto-Hahn-Straße 15, 44227 Dortmund, Germany
  • dAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK   Email: a.s.nelson@leeds.ac.uk
Further Information

Publication History

Received: 30 March 2015

Accepted: 16 April 2015

Publication Date:
19 June 2015 (eFirst)

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.

Supporting Information