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

doi:10.1016/j.tetlet.2020.151632

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

Department of Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-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 language	American English
Journal	Chemistry: Faculty Publications and Other Works
Volume	61
Issue number	12
DOIs	https://doi.org/10.1016/j.tetlet.2020.151632
State	Published - Mar 19 2020

Keywords

Cyclobutanone
Enzyme inhibitor
Transition state mimetic
Strained ring

Disciplines

Biochemistry
Chemistry

Access to Document

10.1016/j.tetlet.2020.151632License: Unspecified

Synthesis of a Protected 2-Aminocyclobutanone as a Modular TransiFinal published version, 2.3 MBLicense: Unspecified

Cite this

@article{5ff28e74c49c4076855784d8699c9725,

title = "Synthesis of a Protected 2-Aminocyclobutanone as a Modular Transition State Synthon for Medicinal Chemistry",

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.",

keywords = "Cyclobutanone, Enzyme inhibitor, Transition state mimetic, Strained ring",

author = "\{Habeeb Mohammad\}, \{Thahani S.\} and Reidl, \{Cory T\} and Matthias Zeller and Becker, \{Daniel P\}",

year = "2020",

month = mar,

day = "19",

doi = "10.1016/j.tetlet.2020.151632",

language = "American English",

volume = "61",

journal = "Chemistry: Faculty Publications and Other Works",

number = "12",

}

TY - JOUR

T1 - Synthesis of a Protected 2-Aminocyclobutanone as a Modular Transition State Synthon for Medicinal Chemistry

AU - Habeeb Mohammad, Thahani S.

AU - Reidl, Cory T

AU - Zeller, Matthias

AU - Becker, Daniel P

PY - 2020/3/19

Y1 - 2020/3/19

N2 - 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.

AB - 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.

KW - Cyclobutanone

KW - Enzyme inhibitor

KW - Transition state mimetic

KW - Strained ring

UR - https://ecommons.luc.edu/chemistry_facpubs/105

U2 - 10.1016/j.tetlet.2020.151632

DO - 10.1016/j.tetlet.2020.151632

M3 - Article

VL - 61

JO - Chemistry: Faculty Publications and Other Works

JF - Chemistry: Faculty Publications and Other Works

IS - 12

ER -

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

Abstract

Keywords

Disciplines

Access to Document

Other files and links

Cite this