title: Ring closing metathesis reactions of α-methylene-β-lactams: application to the synthesis of a simplified phyllostictine analogue with herbicidal activity.
abstract: Ring closing metathesis (RCM) reactions of α-methylene-β-lactams are used to construct strained 11- and 12-membered macrocycles that mimic key structural elements of phyllostictine A. The highest yield and stereoselectivity was achieved making 12-membered macrocycle Z-19 with use of a p-methoxyphenyl group on the lactam nitrogen. Interestingly, substrate concentration had an important influence on the stereochemical course of the reaction. A simplified analogue produced using this approach displays phytotoxic activity against Chlamydomonas reinhardtii suggesting that the α-methylene-β-lactam subunit is responsible, at least in part, for the herbicidal activity of phyllostictine A.
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. m.shipman@warwick.ac.uk.
authors.forename: Samuel
authors.initials: S
authors.lastname: Coe
authors.forename: Nicole
authors.initials: N
authors.lastname: Pereira
authors.forename: Joanna V
authors.initials: JV
authors.lastname: Geden
authors.forename: Guy J
authors.initials: GJ
authors.lastname: Clarkson
authors.forename: David J
authors.initials: DJ
authors.lastname: Fox
authors.forename: Richard M
authors.initials: RM
authors.lastname: Napier
authors.forename: Paul
authors.initials: P
authors.lastname: Neve
authors.forename: Michael
authors.initials: M
authors.lastname: Shipman
mesh_terms: D053961:Azabicyclo Compounds / Q000737:chemistry*; D001384:Azetidines / Q000737:chemistry*; D016825:Chlamydomonas reinhardtii / Q000187:drug effects* / Q000254:growth & development; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C000604103:13-ethyl-4-oxa-13-azabicyclo(10.2.0)tetradec-1-en-14-one; D053961:Azabicyclo Compounds; D001384:Azetidines; D006540:Herbicides; D006575:Heterocyclic Compounds, 3-Ring; C560346:phyllostictine A