6963-32-2Relevant articles and documents
Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines
Fawcett, Alexander,Murtaza, Amna,Gregson, Charlotte H. U.,Aggarwal, Varinder K.
supporting information, (2019/03/26)
Azetidines are important motifs in medicinal chemistry, but there are a limited number of methods for their synthesis. Herein, we present a new method for their modular construction by exploiting the high ring strain associated with azabicyclo[1.1.0]butane. Generation of azabicyclo[1.1.0]butyl lithium followed by its trapping with a boronic ester gives an intermediate boronate complex which, upon N-protonation with acetic acid, undergoes 1,2-migration with cleavage of the central C-N bond to relieve ring strain. The methodology is applicable to primary, secondary, tertiary, aryl, and alkenyl boronic esters and occurs with complete stereospecificity. The homologated azetidinyl boronic esters can be further functionalized through reaction of the N-H azetidine, and through transformation of the boronic ester. The methodology was applied to a short, stereoselective synthesis of the azetidine-containing pharmaceutical, cobimetinib.
An improved, gram-scale synthesis of protected 3-haloazetidines: Rapid diversified synthesis of azetidine-3-carboxylic acids
Ji, Youngran,Wojtas, Lukasz,Lopchuk, Justin M.
, p. 195 - 214 (2018/06/27)
Azetidines are increasingly important heterocycles found in a variety of natural products and pharmaceutical compounds. Protected 3-haloazetidines, widely used and versatile building blocks in medicinal chemistry, have been prepared in a one-pot, gram-scale strain-release reaction of 1-azabicyclo[1.1.0]butane from commercially available starting materials. These intermediates were subsequently used to prepare a series of high value azetidine-3-carboxylic acid derivatives including the first reported synthesis of 1-(tert-butoxy-carbonyl)-3-((trifluoromethyl)thio)azetidine-3-carboxylic acid. (Figure pressented)
Carbonic anhydrase II as host protein for the creation of a biocompatible artificial metathesase
Zhao, Jingming,Kajetanowicz, Anna,Ward, Thomas R.
supporting information, p. 5652 - 5655 (2015/05/27)
An artificial metathesase results from incorporation of an Hoveyda-Grubbs catalyst bearing an arylsulfonamide anchor within human carbonic anhydrase II. The optimization of the catalytic performance is achieved upon combining both chemical and genetic means. Up to 28 TONs were obtained within four hours under aerobic physiological conditions.