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.
Habeeb Mohammad, Thahani S.; Reidl, Cory T.; Zeller, Matthias; and Becker, Daniel P. Ph.D.. Synthesis of a Protected 2-Aminocyclobutanone as a Modular Transition State Synthon for Medicinal Chemistry. Tetrahedron Letters, 61, 12: 151632, 2020. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.1016/j.tetlet.2020.151632
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