Enantioconvergent synthesis of (-)-(2R,5S)-1-allyl-2,5-dimethylpiperazine, an intermediate to delta-opioid receptor ligands.
A convenient, high-yield enantioconvergent synthesis of (-)-1-allyl-(2S,5R)-dimethylpiperazine from trans-2,5-dimethylpiperazine has been developed. This compound is an important intermediate in the synthesis of delta-opioid receptor ligands. The process allows for the laboratory preparation of 100 g quantities of this enantiomerically pure diamine without chromatography. The key steps in the sequence were an efficient optical resolution using relatively inexpensive resolving agents, followed by interconversion of the unwanted (+)-enantiomer into the desired (-)-enantiomer.
Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-0815, USA.
James W
JW
Janetka
M Scott
MS
Furness
Xiaoyan
X
Zhang
Andrew
A
Coop
John E
JE
Folk
Mariena V
MV
Mattson
Arthur E
AE
Jacobson
Kenner C
KC
Rice
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods; D007202:Indicators and Reagents; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C479535:1-allyl-2,5-dimethylpiperazine; D007202:Indicators and Reagents; D008024:Ligands; D010879:Piperazines; D017465:Receptors, Opioid, delta