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Synthesis of Enantiopure PZM21, A Novel Biased Agonist of the Mu-Opioid Receptor
A biased agonist of the mu-opioid receptor
Perrey, D., Zhang, D., Nguyen, T., Carroll, F. I., Ko, M.-C., & Zhang, Y. (2018). Synthesis of Enantiopure PZM21, A Novel Biased Agonist of the Mu-Opioid Receptor: A biased agonist of the mu-opioid receptor. European Journal of Organic Chemistry, (29), 4006-4012. https://doi.org/10.1002/ejoc.201800517
PZM21 (1) was recently reported as a biased agonist of the mu-opioid receptor (MOR) with improved antinociceptive effects and reduced side effects compared with traditional opioid-based analgesics. The original synthesis of PZM21 with the desired (S,S) configuration required the separation of a diastereomeric mixture in the final step by using chiral HPLC. A concise synthesis of 1 has now been developed in the enantiomeric pure form starting with commercially available l-alanine and proceeding via a chiral aziridine as a key intermediate. The final product was obtained as the (S,S) diastereomer in seven steps in 22.5% yield from l-alanine. This synthetic strategy could be readily applied to the development of PZM21 analogues at the thiophenyl position.
