57. Enantioselective Total Synthesis of 5-Phenylmorphans and Cis-Octahydroisoquinolines

Medicinal and Biological Chemistry2020 to PresentSynthetic Organic MethodologyDelta Opioid Receptor
Written By Altmaniacs
 
 

Mahgoub, A.; Khamrai, J.; Festus, O.; Altman, R.*

ChemRxiv 2025, https://doi.org/10.26434/chemrxiv-2025-m3v4p-v2

Modifications of morphine have delivered novel opioid scaffolds, such as 5-phenylmorphans and cis-octahydroisoquinolines, that exhibit various pharmacological profiles. Herein, we disclose the first enantioselective total syntheses of both scaffolds. These syntheses exploit an enantioselective conjugate addition, followed by conver-sion of the ester to a common amine intermediate. Subsequently, a diastereoselective aza-Michael reaction generates 5-phenylmorphans, while a γ-regio- and diastereoselective Mannich reaction generates cis-octahydroisoquinolines.

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