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Angew Chem Int Ed Engl
; 62(51): e202311583, 2023 Dec 18.
Article
in English
| MEDLINE
| ID: mdl-37819253
ABSTRACT
1-Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2 S-NCO, to give spirocyclic ß-lactams. Reduction of the ß-lactam ring with alane produced 1-azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent-free analogue with high activity.