DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integr...DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integrating privileged scaffold dihydroquinazoline that has demonstrated a variety of diverse bioactivities.Driven by the requirement of parallel combinatorial synthesis,we here report a facile synthesis of on-DNA dihydroquinazolinone from aldehyde and anthranilamide.This DNA-compatible reaction was promoted by antimony trichloride,which has been proven to accelerate the reaction and improve conversions.Notably,the broad substrate scope of aldehydes and anthranilamides was explored under the mild reaction condition to achieve moderate-to-excellent conversion yields.We further applied the reaction into on-DNA macrocyclization,obtaining macrocycles embedded dihydroquinazolinone scaffold in synthetically useful conversion yields.展开更多
Herein, an electrocatalytic protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-one has been disclosed. Methanol is activated and utilized as the C1 source to cyclize with 2-aminobenzamides.This cyclization reac...Herein, an electrocatalytic protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-one has been disclosed. Methanol is activated and utilized as the C1 source to cyclize with 2-aminobenzamides.This cyclization reaction proceeds conveniently(room temperature and air atmosphere) without any homogeneous metal catalysts, external oxidants, or bases. A wide variety of N,N-disubstituted 2,3-dihydroquinazolin-4(1H)-ones are obtained via this approach. Moreover, when methanol-d4is used, a deuterated methylene motif is incorporated into the N-heterocycles, providing an efficient approach to the deuterated N-heterocycles.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.22222702,22107016,22107017 and 21907011)the Fundamental Research Funds for the Central Universities(No.2022CDJQY-001)+3 种基金Beijing National Laboratory for Molecular Sciences(No.BNLMS202104)the Natural Science Foundation of Chongqing(Nos.cstc2020jcyj-jqX0009,cstc2021jcyjmsxmX0016 and cstc2021jcyj-cxttX0002)High-end Foreign Expert Introduction Program(No.G2022165020L)Shenzhen Innovation Center for Small Molecule Drug Discovery Co.(No.H20220687).
文摘DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integrating privileged scaffold dihydroquinazoline that has demonstrated a variety of diverse bioactivities.Driven by the requirement of parallel combinatorial synthesis,we here report a facile synthesis of on-DNA dihydroquinazolinone from aldehyde and anthranilamide.This DNA-compatible reaction was promoted by antimony trichloride,which has been proven to accelerate the reaction and improve conversions.Notably,the broad substrate scope of aldehydes and anthranilamides was explored under the mild reaction condition to achieve moderate-to-excellent conversion yields.We further applied the reaction into on-DNA macrocyclization,obtaining macrocycles embedded dihydroquinazolinone scaffold in synthetically useful conversion yields.
基金financial support from the National Natural Science Foundation of China (No. 22061036)the program for youth science and technology innovation leader of Xinjiang Bingtuan (Nos. 2019CB026, CXRC201601)。
文摘Herein, an electrocatalytic protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-one has been disclosed. Methanol is activated and utilized as the C1 source to cyclize with 2-aminobenzamides.This cyclization reaction proceeds conveniently(room temperature and air atmosphere) without any homogeneous metal catalysts, external oxidants, or bases. A wide variety of N,N-disubstituted 2,3-dihydroquinazolin-4(1H)-ones are obtained via this approach. Moreover, when methanol-d4is used, a deuterated methylene motif is incorporated into the N-heterocycles, providing an efficient approach to the deuterated N-heterocycles.
