Synthesis and biological evaluation of a phosphonate analog of the natural acetyl cholinesterase inhibitor cyclophostin.
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.
Bandyopadhyay
Saibal
S
Department of Chemistry and Biochemistry, University of Missouri-St. Louis, 1 University Boulevard, St. Louis, Missouri 63121, USA.
Dutta
Supratik
S
Spilling
Christopher D
CD
Dupureur
Cynthia M
CM
Rath
Nigam P
NP
D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D003500:Cyclization; D006865:Hydrogenation; D007783:Lactones; D063065:Organophosphonates / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007783:Lactones; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C083659:cyclophostin