A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regiosel...A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regioselective access to unprecedented polyarene-fused ten-membered lactams bearing a bridged aryl-aryl-indole scaffold in moderate to good yields.This protocol demonstrates a broad substrate scope,good compatibility with substituents and complete regioselectivity,providing an organocatalytic modular synthetic strategy for creating medium-sized lactams.展开更多
Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridg...Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.展开更多
Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side...Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side chains.These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways.Stachbotrydial(2)with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines.In the present work,an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono-and diamines in the fungus Stachybotrys chartarum cultures.In total,24 phenylspirodrimane lactams(1,3-25)including 18 new compounds were synthesized.Among them,stachybocin A(1),a bioactive phenylspirodrimane lactam dimer,was produced with the yield of 18.7 mg/g of cell dry weight.The structures of these compounds were elucidated by extensive spectroscopic data,single-crystal X-ray diffraction(Cu Kα),and calculated electronic circular dichroism(ECD)analyses.Bioassay revealed that compounds 1,17,and 24 displayed significant inhibitory effect on the inactivated state of hNav 1.2 channels with IC_(50) values of 0.22,2.08,and 0.53μmol/L,respectively.In addition,1 showed potent protein tyrosine phosphatase 1B(PTP1B)inhibitory N-methyl-b-aspartate(NMDA)receptor antagonistic,and anti-inflammatory activities.展开更多
Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reductio...Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.展开更多
The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a sat...The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a satisfactory yield under mild conditions. This method makes it possible to reduce undesirable byproducts.展开更多
Herein,we describe a direct route for the synthesis of 3-gem-difluorovinyl lactams through Zn-mediated reductive hydrodehalogenation.Importantly,by using inexpensive deuterium oxide(D_(2)O),the high value-added vicina...Herein,we describe a direct route for the synthesis of 3-gem-difluorovinyl lactams through Zn-mediated reductive hydrodehalogenation.Importantly,by using inexpensive deuterium oxide(D_(2)O),the high value-added vicinal dideuterated gem-difluoroalkenes with excellent deuterium(D)incorporation were prepared.Mechanism studies indicated a successive single electron transfer process:the reaction initially undergoes hydrodechlorination to give the intermediateα-trifluoromethylidene lactams,which are then activated by the in-situ generated zinc cations and reduced to the desired product via hydrodefluorination.展开更多
Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catal...Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catalysts in organic synthesis.The development of synthetic methods to obtain such chiral compounds has received widespread attention,among which catalytically atroposelective ring-opening of configurationally labile compounds represents one of the most attractive strategies.Various substrates with strained cyclic structures,such as the renowned Bringmann's lactones,can undergo asymmetric transformation into stable atropisomers.Known advancement primarily relies on metal catalyst combined with well-designed chiral ligands,the approaches utilizing organocatalysis as a critical resolution strategy are notably scarce.In this study,we disclosed a N-heterocyclic carbene(NHC)-catalyzed asymmetric ring-opening reaction of biaryl lactams via direct atroposelective nucleophilic activation.The optimized bulky carbene catalyst ensures that the reaction can proceed under mild conditions,affording the desired product with good to excellent yields and atroposelectivity.展开更多
Comprehensive Summary A novel visible-light-induced radical cascade 6-endo cyclization of dienes(N-(2-vinylphenyl)acryl amides)is developed utilizingα-carbonyl bromides as alkyl reagents.This approach affords an effi...Comprehensive Summary A novel visible-light-induced radical cascade 6-endo cyclization of dienes(N-(2-vinylphenyl)acryl amides)is developed utilizingα-carbonyl bromides as alkyl reagents.This approach affords an efficient way for synthesizing six-membered benzo-fused lactam derivatives with chemo-and regio-selectivity and good functional group tolerance.Primary,secondary,and tertiary bromides are well-compatible with this cascade cyclization reaction.展开更多
A non-noble metal catalyzed hydrative cyclization of aldehyde-ynamides for efficient and practical synthesis of medium-sized lactams(7-to 9-membered rings)is disclosed.Compared with previous hydrative cyclization for ...A non-noble metal catalyzed hydrative cyclization of aldehyde-ynamides for efficient and practical synthesis of medium-sized lactams(7-to 9-membered rings)is disclosed.Compared with previous hydrative cyclization for the formation of six-membered lactams(cis-form),a totally inverse diastereoselectivity(trans-form)of medium-sized lactams is observed.In addition,this protocol delivers valuable medium-sized lactams in moderate to good yields with high diastereoselectivities.Moreover,a rational mechanism to understand this inversion of diastereoselectivity is proposed based on theoretical calculations.展开更多
Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ort...Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis.Notably,this privileged strategy is limited to constructing a C–C chiral axis.Herein,organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time,allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C–N chiral axis in excellent yields and atroposelectivities.In addition to the N-arylindole skeleton,N-aryl thieno[3,2-b]pyrrole,furo[3,2-b]pyrrole,and pyrrolo[2,3-b]pyridine skeletons are also compatible with this transformation.This transition-metal-free facile strategy features a broad substrate scope,mild reaction conditions,easy scale-up and excellent atom economy.Several potentially valuable molecules,such as axially chiral peptides,were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters,demonstrating the power of this strategy.展开更多
Medium-sized nitrogen heterocycles,including eightmembered lactams,are important in synthetic and pharmaceutical chemistry because of their presence in a variety of natural products and drug molecules.Previous attempt...Medium-sized nitrogen heterocycles,including eightmembered lactams,are important in synthetic and pharmaceutical chemistry because of their presence in a variety of natural products and drug molecules.Previous attempts at synthesis using a direct headto-tail cyclization strategy suffered from competitive self-cyclization and oligomerization of dipolar species.Herein,we propose an alternative strategy.展开更多
The steric-switched ipso-defluoroamination-triggered and ipso-defluorooxylation-triggered cyclization of(trifluoromethyl)alkenes with amino alcohols and diamines are achieved under mild conditions. This regioselective...The steric-switched ipso-defluoroamination-triggered and ipso-defluorooxylation-triggered cyclization of(trifluoromethyl)alkenes with amino alcohols and diamines are achieved under mild conditions. This regioselective strategy distinguishes the different nucleophilic heteroatom sites in amino alcohols and unsymmetric diamines by the sequential defluorinative functionalization of two C(sp^(3))–F bonds in a CF_(3) group. Various attractive monofluoroalkene-masked medium-sized heterocyclic lactams and lactones are obtained in moderate to excellent yields. Simple derivation of these masked-heterocycles efficiently affords useful skeletons of lactams, lactones, and 1,4-oxazepanes in a single diastereoisomer. Mechanism studies indicate that a unique sequential ipso-/γ-selective defluorinative functionalization pathway is involved in these transformations.展开更多
Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products.Owing to the unfavorable enthalpic and entropic barriers during the transition states,access to medium-...Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products.Owing to the unfavorable enthalpic and entropic barriers during the transition states,access to medium-sized rings is challenging.Herein,a general and practical electrochemical ringexpansion protocol has been developed from commercially available benzocyclic ketones and amides.In this regard,a series of highly functionalized eightto eleven-membered lactams could be successfully accessed in high yields and efficiencies.展开更多
基金National Natural Science Foundation of China(Nos.21971090 and 22271123)the NSF of Jiangsu Province(No.BK20230201)+1 种基金the Natural Science Foundation of Jiangsu Education Committee(No.22KJB150024)the Natural Science Foundation of Jiangsu Normal University(No.21XSRX010)。
文摘A new oxidative N-heterocyclic carbene(NHC)-catalyzed high-order[7+3]annulation reaction ofγ-indolyl phenols as 1,7-dinucleophiles andα,β-alkynals with the aid of Sc(OTf)_(3)is reported,enabling the highly regioselective access to unprecedented polyarene-fused ten-membered lactams bearing a bridged aryl-aryl-indole scaffold in moderate to good yields.This protocol demonstrates a broad substrate scope,good compatibility with substituents and complete regioselectivity,providing an organocatalytic modular synthetic strategy for creating medium-sized lactams.
基金National Natural Science Foundation of China(NSFC,Nos.21772032,21877206,and 22101074)the 111 Project(No.D17007)+3 种基金Excellent Youth Foundation of Henan Scientific Committee(No.222300420012)China Postdoctoral Science Foundation(No.2019M660173)the Natural Science Foundation of Henan Province(No.202300410233)Henan Key Laboratory of Organic Functional Molecules and Drug Innovation for financial support。
文摘Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.
基金financially supported by National Natural Science Foundation of China(No.81803403)CAMS Innovation Fund for Medical Sciences(Nos.CIFMS-2022-I2M-JB-011 and CIFMS-2021-12M-1-029).
文摘Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side chains.These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways.Stachbotrydial(2)with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines.In the present work,an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono-and diamines in the fungus Stachybotrys chartarum cultures.In total,24 phenylspirodrimane lactams(1,3-25)including 18 new compounds were synthesized.Among them,stachybocin A(1),a bioactive phenylspirodrimane lactam dimer,was produced with the yield of 18.7 mg/g of cell dry weight.The structures of these compounds were elucidated by extensive spectroscopic data,single-crystal X-ray diffraction(Cu Kα),and calculated electronic circular dichroism(ECD)analyses.Bioassay revealed that compounds 1,17,and 24 displayed significant inhibitory effect on the inactivated state of hNav 1.2 channels with IC_(50) values of 0.22,2.08,and 0.53μmol/L,respectively.In addition,1 showed potent protein tyrosine phosphatase 1B(PTP1B)inhibitory N-methyl-b-aspartate(NMDA)receptor antagonistic,and anti-inflammatory activities.
基金supported by the National Natural Science Foundation of China (Nos. 21432004 and 21890732)
文摘Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.
文摘The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a satisfactory yield under mild conditions. This method makes it possible to reduce undesirable byproducts.
基金the Guangdong Basic and Applied Basic Research Foundation(2023A1515012657,2024A1515012128)Scientific Research Project of General Universities in Guangdong Province(2022KTSCX046)+3 种基金Zhanjiang Ocean Young Talent Innovation Project(2023E0002,2022E05008)the Fifth-level Research Fund of Guangdong Medical University(4RS23002a,4SG24248G)the Third-level Research Fund of Guangdong Medical University(4RS23002d,4SG22247G)Songshan Lake Medical and Engineering Integration Innovation Project of Guangdong Medical University(4SG22308P)for support.
文摘Herein,we describe a direct route for the synthesis of 3-gem-difluorovinyl lactams through Zn-mediated reductive hydrodehalogenation.Importantly,by using inexpensive deuterium oxide(D_(2)O),the high value-added vicinal dideuterated gem-difluoroalkenes with excellent deuterium(D)incorporation were prepared.Mechanism studies indicated a successive single electron transfer process:the reaction initially undergoes hydrodechlorination to give the intermediateα-trifluoromethylidene lactams,which are then activated by the in-situ generated zinc cations and reduced to the desired product via hydrodefluorination.
基金the Natural Science Foundation of Jiangsu Province(BK20221309)the National Natural Science Foundation of China(21602105).
文摘Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catalysts in organic synthesis.The development of synthetic methods to obtain such chiral compounds has received widespread attention,among which catalytically atroposelective ring-opening of configurationally labile compounds represents one of the most attractive strategies.Various substrates with strained cyclic structures,such as the renowned Bringmann's lactones,can undergo asymmetric transformation into stable atropisomers.Known advancement primarily relies on metal catalyst combined with well-designed chiral ligands,the approaches utilizing organocatalysis as a critical resolution strategy are notably scarce.In this study,we disclosed a N-heterocyclic carbene(NHC)-catalyzed asymmetric ring-opening reaction of biaryl lactams via direct atroposelective nucleophilic activation.The optimized bulky carbene catalyst ensures that the reaction can proceed under mild conditions,affording the desired product with good to excellent yields and atroposelectivity.
基金supported by the National Natural Science Foundation of China(22078084 and 51874132)the Scientific Research Fund of Hunan Provincial Education Department(22B0674)the Science and Natural Science Foundation of Hunan Province(No.2023JJ30273 and 2023JJ40301).
文摘Comprehensive Summary A novel visible-light-induced radical cascade 6-endo cyclization of dienes(N-(2-vinylphenyl)acryl amides)is developed utilizingα-carbonyl bromides as alkyl reagents.This approach affords an efficient way for synthesizing six-membered benzo-fused lactam derivatives with chemo-and regio-selectivity and good functional group tolerance.Primary,secondary,and tertiary bromides are well-compatible with this cascade cyclization reaction.
基金supported by the National Natural Science Foundation of China(92056104 and 21772161)the Natural Science Foundation of Fujian Province of China(2019J02001)+3 种基金the President Research Funds from Xiamen University(20720210002)the National Fund for Fostering Talents of Basic Science(NFFTBS)(J1310024)the Opening Project of PCOSS,Xiamen University(201909)the Bioinformatics Center of Nanjing Agricultural University and the Start-up Research Fund of Nanjing Agricultural University(050-804099)。
文摘A non-noble metal catalyzed hydrative cyclization of aldehyde-ynamides for efficient and practical synthesis of medium-sized lactams(7-to 9-membered rings)is disclosed.Compared with previous hydrative cyclization for the formation of six-membered lactams(cis-form),a totally inverse diastereoselectivity(trans-form)of medium-sized lactams is observed.In addition,this protocol delivers valuable medium-sized lactams in moderate to good yields with high diastereoselectivities.Moreover,a rational mechanism to understand this inversion of diastereoselectivity is proposed based on theoretical calculations.
基金supported by the National Key Research and Development Program of China (2017YFA0204704)the General Program of Chongqing Natural Science Foundation Project (cstc2020jcyjmsxmX0712)+2 种基金Ningbo Natural Science Foundation (202003N4063)the National Natural Science Foundation of China (21602105, 22174065)the Natural Science Foundation of Jiangsu Province (BK20171460)。
文摘Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis.Notably,this privileged strategy is limited to constructing a C–C chiral axis.Herein,organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time,allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C–N chiral axis in excellent yields and atroposelectivities.In addition to the N-arylindole skeleton,N-aryl thieno[3,2-b]pyrrole,furo[3,2-b]pyrrole,and pyrrolo[2,3-b]pyridine skeletons are also compatible with this transformation.This transition-metal-free facile strategy features a broad substrate scope,mild reaction conditions,easy scale-up and excellent atom economy.Several potentially valuable molecules,such as axially chiral peptides,were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters,demonstrating the power of this strategy.
基金from the National Natural Science Foundation of China(nos.21822103,21772052,21772053,21820102003,and 91956201)the Program of Introducing Talents of Discipline to Universities of China(111 Program,B17019)the Natural Science Foundation of Hubei Province(no.2017AHB047)。
文摘Medium-sized nitrogen heterocycles,including eightmembered lactams,are important in synthetic and pharmaceutical chemistry because of their presence in a variety of natural products and drug molecules.Previous attempts at synthesis using a direct headto-tail cyclization strategy suffered from competitive self-cyclization and oligomerization of dipolar species.Herein,we propose an alternative strategy.
基金supported by the National Natural Science Foundation of China (21702064)the Guangdong Basic and Applied Basic Research Foundation (2020B1515020012)。
文摘The steric-switched ipso-defluoroamination-triggered and ipso-defluorooxylation-triggered cyclization of(trifluoromethyl)alkenes with amino alcohols and diamines are achieved under mild conditions. This regioselective strategy distinguishes the different nucleophilic heteroatom sites in amino alcohols and unsymmetric diamines by the sequential defluorinative functionalization of two C(sp^(3))–F bonds in a CF_(3) group. Various attractive monofluoroalkene-masked medium-sized heterocyclic lactams and lactones are obtained in moderate to excellent yields. Simple derivation of these masked-heterocycles efficiently affords useful skeletons of lactams, lactones, and 1,4-oxazepanes in a single diastereoisomer. Mechanism studies indicate that a unique sequential ipso-/γ-selective defluorinative functionalization pathway is involved in these transformations.
基金the National Natural Science Foundation of China(no.21520102003)the Hubei Province Natural Science Foundation of China(no.2017CFA010)the Program of Introducing Talents of Discipline to Universities of China(111 Program)for their generous financial support.
文摘Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products.Owing to the unfavorable enthalpic and entropic barriers during the transition states,access to medium-sized rings is challenging.Herein,a general and practical electrochemical ringexpansion protocol has been developed from commercially available benzocyclic ketones and amides.In this regard,a series of highly functionalized eightto eleven-membered lactams could be successfully accessed in high yields and efficiencies.
