title: Studies towards the synthesis of indolizin-5(3H)-one derivatives and related 6,5-azabicyclic scaffolds by ring-closing metathesis.
abstract: Herein, we report on work towards the development of a new strategy for the synthesis of rare and biologically interesting indolizin-5(3H)-ones, which is based around the use of ring-closing metathesis to construct the carbocyclic ring system. This study has provided insights into the general stability of indolizin-5(3H)-ones and their tendency to exist as the tautomeric indolizin-5-ols. Furthermore, this approach has allowed access to other novel structurally related compounds based around unusual 6,5-azabicyclic scaffolds, which are also difficult to generate using typical methods. The azabicyclic compounds synthesized in this study reside in attractive regions of heterocyclic chemical space that are underexploited in current drug and agrochemical discovery efforts.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Frei
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Bilyard
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Alanine
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
authors.forename: Warren R J D
authors.initials: WR
authors.lastname: Galloway
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Stokes
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK; Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: spring@ch.cam.ac.uk.
authors.forename: David R
authors.initials: DR
authors.lastname: Spring
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D007212:Indolizines / Q000138:chemical synthesis*; D015394:Molecular Structure
chemical_list: D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D007212:Indolizines
keywords: Heterocycles; Libraries; Metathesis; Scaffold; Synthetic methodology