Enantioselective synthesis of the excitatory amino acid (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid.
An enantioselective synthesis of the alpha,alpha-dialkyl-alpha-amino acid (1S,3R)-ACPD has been achieved using an alkylidene carbene 1,5-CH insertion reaction as a key step. The ketone cyclization precursor was synthesized from Garner's aldehyde in high yield via a Wittig homologation and subsequent catalytic hydrogenation. Treatment of the ketone with 1.2 equiv of lithio(trimethylsilyl)diazomethane in THF resulted in the formation of the corresponding cyclopentene-containing CH-insertion product in 62-69% yield in high enantiomeric excess. Subsequent functional group manipulation allowed the synthesis of the amino acid (1S,3R)-ACPD to be completed.
Bradley
Daniel M
DM
The School of Chemistry, University of Nottingham, University Park, UK.
Mapitse
Renameditswe
R
Thomson
Nicholas M
NM
Hayes
Christopher J
CJ
D003515:Cycloleucine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D018846:Excitatory Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D018846:Excitatory Amino Acids; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane