Synthesis of a protected 2-aminocyclobutanone as a modular transition state synthon for medicinal chemistry

TETRAHEDRON LETTERS

卷:61

Article

Mohammad, Thahani S. Habeeb¹  Reidl, Cory T.²  Zeller, Matthias³  Becker, Daniel P.¹ 

[1] Loyola Univ Chicago, Dept Chem & Biochem, Chicago, IL 60660 USA

[2] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA

[3] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

关键词: Cyclobutanone;    Enzyme inhibitor;    Transition state mimetic;    Strained ring;   

DOI  :  10.1016/j.tetlet.2020.151632

来源: Elsevier

【 摘 要 】

The hydrochloride salt of alpha-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 alpha-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. (C) 2020 Elsevier Ltd. All rights reserved.

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