title: Synthesis and biological evaluation of a phosphonate analog of the natural acetyl cholinesterase inhibitor cyclophostin.
abstract: Two diastereomers of a phosphonate analog 6 of the AChE inhibitor cyclophostin were synthesized. The substitution reaction of phosphono allylic carbonate 10a with methyl acetoacetate gave the vinyl phosphonate 9a. Attempted hydrogenation/debenzylation gave an unexpected enolether lactone. Alternatively, selective hydrogenation, demethylation, cyclization and debenzylation gave the phosphonate analog of cyclophostin as a separable mixture of diastereomers 6. The trans phosphonate isomer was more active than the cis isomer against AChE from two sources.
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri-St. Louis, 1 University Boulevard, St. Louis, Missouri 63121, USA.
authors.forename: Saibal
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Supratik
authors.initials: S
authors.lastname: Dutta
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Spilling
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Dupureur
authors.forename: Nigam P
authors.initials: NP
authors.lastname: Rath
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D003500:Cyclization; D006865:Hydrogenation; D007783:Lactones; D063065:Organophosphonates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D007783:Lactones; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C083659:cyclophostin