Comprehensive Summary.Herein, an intermolecular palladium(II)-catalyzed regioselective [4+2] benzannulation reaction capable of converting 2-pyridones into quinolinones was developed using electron-deficient alkenes a...Comprehensive Summary.Herein, an intermolecular palladium(II)-catalyzed regioselective [4+2] benzannulation reaction capable of converting 2-pyridones into quinolinones was developed using electron-deficient alkenes as two-carbon units. An examination of the reaction mechanism indicated that the extension from 2-pyridone to quinolinone was likely facilitated through a series of sequential C—H activation reactions or 6π electrocyclization, culminating in dehydrogenative aromatization. This method of diversity-oriented synthesis of quinolinone derivatives is characterized by a broad substrate scope, atom economy, and excellent chemical selectivity. In addition, these quinolinone derivatives exhibit fluorescent absorption within the visible-light spectrum, which makes them suitable candidates for the development of innovative fluorescent probes.展开更多
Flavones and isoflavones are recognized as privileged heterocyclic scaffolds for the preparation of bioactive compounds.Efficient methods to access these heterocycles are in urgent need.Herein,we report diversity-orie...Flavones and isoflavones are recognized as privileged heterocyclic scaffolds for the preparation of bioactive compounds.Efficient methods to access these heterocycles are in urgent need.Herein,we report diversity-oriented synthesis of flavones and isoflavones from 3-iodochromones via palladium/norbornene cooperative catalysis.The success of this research relies on the use of a unique bridge-head ester modified norbornene derivative as the mediator.Salient features of this include readily available starting materi-als regarding 3-iodochromones,ortho-C-H arylating and alkylating reagents and ipso-terminating reagents,broad substrate scope,good chemoselectivity,good step-economy and scalability.A large number of structurally diversified flavones,isoflavones and 2,3-diarylated chromones can be quickly prepared in a predictable manner.As showcased by the efficient formal synthesis of um-bralisib,this chemistry can be treated as another valuable addition to the toolbox of medicinal chemists.展开更多
Diversity-oriented synthesis （DOS） has been widely applied in the generation of a large collection of highly functionalized molecules with diverse chemical skeletons. Herein, we report the diversity-oriented synthes...Diversity-oriented synthesis （DOS） has been widely applied in the generation of a large collection of highly functionalized molecules with diverse chemical skeletons. Herein, we report the diversity-oriented synthesis of a series of structurally diverse bicyclic substrates via an efficient tandem conjugate addition/aldol process followed by ring-closing metathesis （RCM）. This approach allows us to efficiently prepare a number of structurally complex molecules for the further chemical biology studies.展开更多
The selective introduction of fluorine atoms into drug candidates has long been used as a common strategy in drug discovery.Most methods used for the synthesis of tertiary aliphatic fluorides rely on C–F bond formati...The selective introduction of fluorine atoms into drug candidates has long been used as a common strategy in drug discovery.Most methods used for the synthesis of tertiary aliphatic fluorides rely on C–F bond formation by fluorinating relatively stable tertiary carbon cation or radical intermediates,where the stoichiometric amounts of corrosive/expensive electrophilic fluorinating reagents were required.展开更多
Presented here is a one-pot strategy starting from rationally designed macrocyclic precursors for the diverse construction of sophisticated ultracycles.The type and amount of the base were found to significantly influ...Presented here is a one-pot strategy starting from rationally designed macrocyclic precursors for the diverse construction of sophisticated ultracycles.The type and amount of the base were found to significantly influence the macrocyclization outcome.The use of 4.0 equiv.CsF resulted in ultracycles of both types A and B while the presence of CsF larger than 6.0 equiv.produced only type B ultracycles.Existence of anion template increased the total yields and affected the distribution of the ultracycles.The ultracycles can accommodate large organic dicarboxylates anions via multiple anion-πand hydrogen bonds,and show selectivity to the size-matched heptanedioate(C7^(2−)).Based on all possible species and relevant equilibrium constants as well as material and charge balances,a numerical iterative algorithm was developed and applied to fit the association constants of B2H with dicarboxylates from glutarate(C5^(2−))to octanedioate(C8^(2−)),which gave association constants up to 10^(3) L/mol.展开更多
Click chemistry has become a useful tool for diverse molecular linkage and modification, and the development of new click strategy that enable reversibility and multifunctionality is of high demand for the multifuncti...Click chemistry has become a useful tool for diverse molecular linkage and modification, and the development of new click strategy that enable reversibility and multifunctionality is of high demand for the multifunction and drug release. Herein, compositionally clicking combined regioselective iridium-catalyzed azide-alkynthio cycloaddition(Ir-AAC) and disulfuration has been developed for the sequential linkage from N-acetylenethio phthalimides, naturally occurring thiols and readily available azides. This method has been successfully applied to the construction of drug hybrids, peptide modification and glycosylation. Furthermore, by the design of diacetylenethio phthalimide as a platform molecule, trifunctional conjugants were sequentially linked through independent Ir-AAC, disulfuration and Cu-AAC reaction for hydrophobic tagging ternary PROTACs.展开更多
基金the Natural Science Foundation of Anhui University of Chinese Medicine(2021rczd003 and 2022AH050440)the Cooperation Project of Fuyang Municipal Government and Fuyang Normal University(No.SXHZ202002)+1 种基金the Natural Science Foundation of Fuyang Normal University(FYKFKT24001)the National Natural Science Foundation of China(Grant No.22301074)for financial support.
文摘Comprehensive Summary.Herein, an intermolecular palladium(II)-catalyzed regioselective [4+2] benzannulation reaction capable of converting 2-pyridones into quinolinones was developed using electron-deficient alkenes as two-carbon units. An examination of the reaction mechanism indicated that the extension from 2-pyridone to quinolinone was likely facilitated through a series of sequential C—H activation reactions or 6π electrocyclization, culminating in dehydrogenative aromatization. This method of diversity-oriented synthesis of quinolinone derivatives is characterized by a broad substrate scope, atom economy, and excellent chemical selectivity. In addition, these quinolinone derivatives exhibit fluorescent absorption within the visible-light spectrum, which makes them suitable candidates for the development of innovative fluorescent probes.
基金Weare grateful to the National Natural Science Foundation of China(Grants 21871213,21801193 and 22071189)the start-up funding from Wuhan University for financial support。
文摘Flavones and isoflavones are recognized as privileged heterocyclic scaffolds for the preparation of bioactive compounds.Efficient methods to access these heterocycles are in urgent need.Herein,we report diversity-oriented synthesis of flavones and isoflavones from 3-iodochromones via palladium/norbornene cooperative catalysis.The success of this research relies on the use of a unique bridge-head ester modified norbornene derivative as the mediator.Salient features of this include readily available starting materi-als regarding 3-iodochromones,ortho-C-H arylating and alkylating reagents and ipso-terminating reagents,broad substrate scope,good chemoselectivity,good step-economy and scalability.A large number of structurally diversified flavones,isoflavones and 2,3-diarylated chromones can be quickly prepared in a predictable manner.As showcased by the efficient formal synthesis of um-bralisib,this chemistry can be treated as another valuable addition to the toolbox of medicinal chemists.
文摘Diversity-oriented synthesis （DOS） has been widely applied in the generation of a large collection of highly functionalized molecules with diverse chemical skeletons. Herein, we report the diversity-oriented synthesis of a series of structurally diverse bicyclic substrates via an efficient tandem conjugate addition/aldol process followed by ring-closing metathesis （RCM）. This approach allows us to efficiently prepare a number of structurally complex molecules for the further chemical biology studies.
基金the National Science Foundation of China(nos.21971228 and 21772187)for financial support.
文摘The selective introduction of fluorine atoms into drug candidates has long been used as a common strategy in drug discovery.Most methods used for the synthesis of tertiary aliphatic fluorides rely on C–F bond formation by fluorinating relatively stable tertiary carbon cation or radical intermediates,where the stoichiometric amounts of corrosive/expensive electrophilic fluorinating reagents were required.
基金support from the National Natural Science Foundation of China(Nos.22171271,22022112)Beijing National Laboratory for Molecular Sciences(No.BNLMS-CXXM-202002)。
文摘Presented here is a one-pot strategy starting from rationally designed macrocyclic precursors for the diverse construction of sophisticated ultracycles.The type and amount of the base were found to significantly influence the macrocyclization outcome.The use of 4.0 equiv.CsF resulted in ultracycles of both types A and B while the presence of CsF larger than 6.0 equiv.produced only type B ultracycles.Existence of anion template increased the total yields and affected the distribution of the ultracycles.The ultracycles can accommodate large organic dicarboxylates anions via multiple anion-πand hydrogen bonds,and show selectivity to the size-matched heptanedioate(C7^(2−)).Based on all possible species and relevant equilibrium constants as well as material and charge balances,a numerical iterative algorithm was developed and applied to fit the association constants of B2H with dicarboxylates from glutarate(C5^(2−))to octanedioate(C8^(2−)),which gave association constants up to 10^(3) L/mol.
基金supported by the National Natural Science Foundation of China (Nos. 21901179 and 22125103)the Scientific Activities of Selected Returned Overseas Professionals of Shanxi Province (No. 20200002)+1 种基金the Natural Science Foundation of Shanxi Province (No. 202103021224067)the Research Project of Shanxi Scholarship Council (No. HGKY2019029)。
文摘Click chemistry has become a useful tool for diverse molecular linkage and modification, and the development of new click strategy that enable reversibility and multifunctionality is of high demand for the multifunction and drug release. Herein, compositionally clicking combined regioselective iridium-catalyzed azide-alkynthio cycloaddition(Ir-AAC) and disulfuration has been developed for the sequential linkage from N-acetylenethio phthalimides, naturally occurring thiols and readily available azides. This method has been successfully applied to the construction of drug hybrids, peptide modification and glycosylation. Furthermore, by the design of diacetylenethio phthalimide as a platform molecule, trifunctional conjugants were sequentially linked through independent Ir-AAC, disulfuration and Cu-AAC reaction for hydrophobic tagging ternary PROTACs.
