An extremely mild method for amide-cleavage by using the triazine-based benzylating reagent 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4-benzylmorpholinium trifluoromethanesulfonate (DPT-BM), which spontaneously releases benzyl cation species when being dissolved at room temperature, has been developed. O-Benzylation of the amide with DPT-BM and the subsequent hydrolysis of the resulting intermediate benzyl imidate salt afford the corresponding amine and benzyl ester, which can be converted by hydrogenolysis into a carboxylic acid under neutral conditions. O-Benzylation proceeds depending on both steric and electronic factors around the amide group. Thus, some amides have been selectively cleaved over other amides. Furthermore, intramolecular chemoselective cleavage of an amide group in the presence of an ester group was achieved. Such selective hydrolytic reactions cannot be performed with Meerwein reagents as well as under acidic or basic hydrolytic conditions.
A new O-benzylating reagent, that is, 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4-benzylmorpholinium trifluoromethanesulfonate (DPT-BM), has been developed. Benzyl cation equivalents are generated from DPT-BM by dissolving the compound in a solvent at room temperature under non-acidic conditions. The benzylation of various alcohols by using a combination of DPT-BM and magnesium oxide provided the benzyl ethers in good yields.
In this study, we evaluated the effect of structural descriptors on the in silico design of bioactive compounds. The authors have proposed a molecular design technique for designing new bioactive compounds. In this approach, known fragments are combined to generate new structures, which are evolved to increase the similarity to a known active compound. We generated the structure of CDK2 inhibitors using four descriptors (three binary fingerprints and a numerical vector) to evaluate the effect of descriptors on the molecular design. Subsequently, the physicochemical properties of the generated compounds were com-pared and evaluated from a similarity viewpoint. As a result, it was clarified that better structures can be generated by using descriptors consisting of numerical vectors rather than binary fingerprints. Moreover, the compound generated using the numerical vector or a long-bit fingerprint resulted in favorable docking scores. Although binary fingerprints such as MACCS are widely used in this field, this result shows that it is important to use numeric vectors, or at least to use long-bit fingerprints, to design drug-like CDK2 inhibitors by the similarity-based structure generation.
An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.
A mild and convenient reaction for oxidative trifluoromethylation of terminal alkenes was developed using in situ generated AgCF 3 in the presence of a copper catalyst. The reaction proceeded under an air atmosphere to afford trifluoromethylated allylic compounds in moderate to good yield. This reaction, with no need for highly hygroscopic or corrosive reagents, features not only a simple operation but also various functional group tolerances.
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