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Synthesis of Enantiopure PZM21: A Biased Agonist of the Mu-Opioid Receptor
- Source :
- European Journal of Organic Chemistry. 2018:4006-4012
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- PZM21 (1) was recently reported as a biased agonist of the mu-opioid receptor (MOR) with improved antinociceptive effects but reduced side effects than traditional opioid-based analgesics. The original synthesis of PZM21 with the desired (S,S) configuration required the separation of diastereomeric mixture in the final step using chiral HPLC. We have designed a concise synthesis of 1 in the enantiomeric pure form starting with commercially available L-alanine and via a chiral aziridine as a key intermediate. The final product 1 as the (S,S) diastereomer was obtained in 7 steps in 22.5% yield from L-alanine. This synthetic strategy could be readily applied to the development of PZM21 analogs at the thiophenyl position.
- Subjects :
- Agonist
010405 organic chemistry
medicine.drug_class
Chemistry
Stereochemistry
Organic Chemistry
Diastereomer
Aziridine
010402 general chemistry
01 natural sciences
0104 chemical sciences
Chiral column chromatography
chemistry.chemical_compound
Enantiopure drug
Yield (chemistry)
medicine
Physical and Theoretical Chemistry
Enantiomer
μ-opioid receptor
Subjects
Details
- ISSN :
- 1434193X
- Volume :
- 2018
- Database :
- OpenAIRE
- Journal :
- European Journal of Organic Chemistry
- Accession number :
- edsair.doi...........1ca6a63ac282056e176f90fa9d221f27