Angew. Chem. Int. Ed. 2023, 62 (51), e202311583
DOI: 10.1002/anie.202311583
Kirichok A.; Tkachuk H.; Kozyriev Y.; Shablykin O.; Datsenko O.; Granat D.; Yegorova T.; Bas Y.; Semirenko V.; Pishel I.; Kubyshkin V.; Klymenko-Ulianov O.; Lesyk D.; Mykhailiuk P.
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 Graf's isocyanate, ClO2S-NCO, into spirocyclic β‑lactams. Reduction of the β-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 the new patent-free analogue with high activity.