Synthesis of a Protected 2-Aminocyclobutanone as a Modular Transition State Synthon for Medicinal Chemistry

Thahani S. Habeeb Mohammad, Cory T Reidl, Matthias Zeller, Daniel P Becker

Research output: Contribution to journalArticlepeer-review

Abstract

The hydrochloride salt of ɑ-aminocyclobutanone protected as its dimethyl acetal 2,2-dimethoxycyclobutan-1-aminium chloride (3) has been prepared as a modular synthon for convenient access to cyclobutanone-containing lead inhibitors of hydrolase enzymes including serine proteases and metalloproteases. Protected ɑ-aminocyclobutanone 3 was converted to representative amide and sulfonamide-functionalized 2-aminocyclobutanone derivatives. Reaction of the amino acetal 3 with phenyl isothiocyanate afforded the bicyclic urea 1-hydroxyl-2,4-diazabicyclo[3.2.0]heptane-3-thione (9) as confirmed by a single crystal X-ray structure.

Original languageAmerican English
JournalChemistry: Faculty Publications and Other Works
Volume61
Issue number12
DOIs
StatePublished - Mar 19 2020

Keywords

  • Cyclobutanone
  • Enzyme inhibitor
  • Transition state mimetic
  • Strained ring

Disciplines

  • Biochemistry
  • Chemistry

Cite this