A novel unsymmetrical squaramide-linked squaraine dye（SQ） has been synthesized through squaramide 3 and semisquaraine 6. The molecular structure of SQ has been characterized by ~1H NMR,IR and MS.Due to the influence...A novel unsymmetrical squaramide-linked squaraine dye（SQ） has been synthesized through squaramide 3 and semisquaraine 6. The molecular structure of SQ has been characterized by ~1H NMR,IR and MS.Due to the influence of the hydrogen bond and the solvent effect,SQ exhibits unique spectral properties compared with typical squaraine dyes.For its excellent ability of binding primary amine,SQ is a promising receptor of recognizing primary amine.展开更多
A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbo n...A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbo nyl compounds to a,β-unsaturated carbonyl compounds in high yields(up to 99%)and good to excellent enantiomeric excesses(up to 99%ee).The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions.Moreover,this strategy also provides valuable and easy access to chiral chromene,naphthoquinone and acetylacetone derivatives,which are important skeletons in biological and pharmaceutical compounds.展开更多
Enantioselective chlorination of b-keto esters and amides catalyzed by squaramide-linked bisoxazoline ligand–Cu（OAc）2complexes was investigated. The corresponding chlorinated products were obtained in excellent yie...Enantioselective chlorination of b-keto esters and amides catalyzed by squaramide-linked bisoxazoline ligand–Cu（OAc）2complexes was investigated. The corresponding chlorinated products were obtained in excellent yields with moderate enantioselectivities. The effect of solvent, temperature, Lewis acid, and ligand structure on the reaction is discussed. This was the first investigation of catalytic asymmetric achlorination of b-keto amides. This study has highlighted that a simple chiral squaramide–oxazoline with cheap Cu（OAc）2 H2 O complexes can catalyze this chlorination.展开更多
Pathogenic strains of Acanthamoeba cause keratitis (AK), granulomatous amoebic encephalitis (GAE), amoebic pneumonitis (AP), and skin infection in human and animals. The treatment of an Acanthamoeba infection is invar...Pathogenic strains of Acanthamoeba cause keratitis (AK), granulomatous amoebic encephalitis (GAE), amoebic pneumonitis (AP), and skin infection in human and animals. The treatment of an Acanthamoeba infection is invariably very difficult and not always effective, and compounds that are amebicidic or amebistatic are frequently toxic and/or irritating for humans. Squaramides and polyamine derivatives have been demonstrated to have antitumor and antiprotozoal activity. The aim of this study was to investigate the activity of 5 squaramides and 5 acyclic polyamines against trophozoites and cysts of A. castellanii Neff. Amoebicidal activity against the trophozoites and cytotoxicity against Vero cells were evaluated with a colorimetric assay, using Alamar Blue?, and chlorhexidine digluconate was assayed as the reference drug. The squaramides 3 and 5 and the acyclic polyamine 6 appeared to be the most active against the trophozoites and their cytotoxicity was low, showing selectivity indexes of 28.3, 26, and 25.7, respectively, similar to the control drug, chlorhexidine digluconate (27.6). But only the squaramide 3 showed complete cysticidal activity at the concentrations of 100 and 200 μM, as the chlorhexidine digluconate. Further studies of the mechanism of action and in vivo assays are needed, but squaramide 3 could be used for developing novel therapeutic approaches against Acanthamoeba infections.展开更多
A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers con...A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic centers.Here,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic transformations.These programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SNU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide centers.Squaramides were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching phenomena.Therefore,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore environments.We then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide ring-opening.Some of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.展开更多
Enantioselective synthesis of biologically active dihydropyrano[2,3-c]pyrazoles has been achieved through a squaramide-catalysed Michael addition/Thorpe-Ziegler type cyclization cascade reaction between arylidenepyra-...Enantioselective synthesis of biologically active dihydropyrano[2,3-c]pyrazoles has been achieved through a squaramide-catalysed Michael addition/Thorpe-Ziegler type cyclization cascade reaction between arylidenepyra-zolones and malononitrile.A series of optically active dihydropyano[2,3-c]pyrazoles were obtained in excellent yields(up to 99%)and moderate to good enantioselectivities(up to 79%ee)under mild reaction conditions.展开更多
Substa ntial progresses have bee n made toward the developme nt of meta I-free catalysts for stereoselective rin g-ope ning polymeriza-tion(ROP)of rac-lactide.Yet the discovery of organic catalysts effective at ambien...Substa ntial progresses have bee n made toward the developme nt of meta I-free catalysts for stereoselective rin g-ope ning polymeriza-tion(ROP)of rac-lactide.Yet the discovery of organic catalysts effective at ambient temperature remains a major challenge.Here,the bifunctional H-bonding catalyst SQ-1 containing a basic tertiary amine and squaramide motif proved to be good candidate for the stereoselective ROP of rac-lactide at room temperature,yielding stereoregular polylactide with controlled molecular weights(up to 21.1 kg/mol)and high tacticity(PjESC up to 0.88).Furthermore,binary H-b on ding catalytic system con sisti ng of squaramides(SQ-2 to SQ-6)and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)could efficiently promote the ROP of rac-lactide at room temperature within short reaction time.Among them,the most bulky squaramide SQ-2 exhibited the best steroselectivity towards the ROP of rac-lactide without transesterification side reactions during the polymerization process.The resulting polylactides were proved to have controlled molecular weights as high as 22.2 kg/mol and narrow distributions(1.10-1.24).展开更多
An efficient enantioselective cascade sulfa-Michael/Michael addition reaction of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl ester with nitroalkenes catalyzed by a chiral squaramide catalyst was disclosed.This c...An efficient enantioselective cascade sulfa-Michael/Michael addition reaction of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl ester with nitroalkenes catalyzed by a chiral squaramide catalyst was disclosed.This cascade reaction afforded thiochroman derivatives with three contiguous stereocenters in high yields(up to 94%),excellent diastereoselectivities(up to>25∶1 dr)and enantioselectivities(up to 99% ee).展开更多
Isosteviol,the hydrolysate of stevioside,has attracted increasing attention from scientists because of its special molecular skeleton and extensive biological activities.In recent years,due to the continuous rise of o...Isosteviol,the hydrolysate of stevioside,has attracted increasing attention from scientists because of its special molecular skeleton and extensive biological activities.In recent years,due to the continuous rise of organocatalysis,an increasing number of organocatalysts based on isosteviol have been devised and synthesized to facilitate a range of highly enantioselective asymmetric synthesis.The isosteviol-type organocatalysts reported in the literature over the past decade and their applications in asymmetric catalysis are systematically analyzed and elaborated in order to provide assistance for the further design,synthesis,and application of organocatalysis derived from isosteviol.展开更多
A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activat...A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activation of 3-aminophenol derivatives and 4-benzylidenepyrrolidine-2,3-diones by the chiral catalyst,enabling an efficient asymmetric oxa-[3+3]-annulation reaction.The protocol exhibits a broad substrate scope with 34 diverse examples,delivering moderate-to-good yields ranging from 64%to 81%,excellent enantioselectivity(up to 99%ee),and tunable diastereoselectivity(dr up to 15:1).Notably,halogen substitution plays a pivotal role in dramatically enhancing stereocontrol,further optimizing the diastereoselectivity of the target products.To validate its practical utility,gram-scale synthesis was successfully conducted without compromising yield or stereoselectivity,and subsequent derivatization reactions confirmed the versatility of the obtained chiral tricyclic chromans.This metal-free,mild reaction system not only enriches the synthetic toolbox for constructing complex chroman architectures,but also provides a versatile platform for the asymmetric synthesis of bioactive molecules containing the chiral tricyclic chroman skeleton,highlighting the significance of enantioselectivity and diastereoselectivity in accessing functionalized heterocyclic compounds.展开更多
The saccharide-based chiral bifunctional thiourea-phosphines were developed as chiral organocatalysts for the intramolecular Morita-Baylis-Hillman reaction of o^-formyl-enones. With only 2 tool% of thiourea-phosphine ...The saccharide-based chiral bifunctional thiourea-phosphines were developed as chiral organocatalysts for the intramolecular Morita-Baylis-Hillman reaction of o^-formyl-enones. With only 2 tool% of thiourea-phosphine cata- lyst 3c, chiral functionalized cyclohexenes were achieved under mild reaction conditions with excellent yields and enantioselectivities.展开更多
基金the National Natural Science Foundation of China(No20702005)the Fujian Provincial Natural Science Foundation of China(No2008J0148)
文摘A novel unsymmetrical squaramide-linked squaraine dye（SQ） has been synthesized through squaramide 3 and semisquaraine 6. The molecular structure of SQ has been characterized by ~1H NMR,IR and MS.Due to the influence of the hydrogen bond and the solvent effect,SQ exhibits unique spectral properties compared with typical squaraine dyes.For its excellent ability of binding primary amine,SQ is a promising receptor of recognizing primary amine.
基金the financial support from the National Natural Science Foundation of China(Nos.21572026 and 21702019)Advanced Catalysis and Green Manufacturing Collabo-rative Innovation Center,Changzhou University,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbo nyl compounds to a,β-unsaturated carbonyl compounds in high yields(up to 99%)and good to excellent enantiomeric excesses(up to 99%ee).The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions.Moreover,this strategy also provides valuable and easy access to chiral chromene,naphthoquinone and acetylacetone derivatives,which are important skeletons in biological and pharmaceutical compounds.
基金financial support from the National Natural Science Foundation of China(Nos.21072010 and 21272024)
文摘Enantioselective chlorination of b-keto esters and amides catalyzed by squaramide-linked bisoxazoline ligand–Cu（OAc）2complexes was investigated. The corresponding chlorinated products were obtained in excellent yields with moderate enantioselectivities. The effect of solvent, temperature, Lewis acid, and ligand structure on the reaction is discussed. This was the first investigation of catalytic asymmetric achlorination of b-keto amides. This study has highlighted that a simple chiral squaramide–oxazoline with cheap Cu（OAc）2 H2 O complexes can catalyze this chlorination.
文摘Pathogenic strains of Acanthamoeba cause keratitis (AK), granulomatous amoebic encephalitis (GAE), amoebic pneumonitis (AP), and skin infection in human and animals. The treatment of an Acanthamoeba infection is invariably very difficult and not always effective, and compounds that are amebicidic or amebistatic are frequently toxic and/or irritating for humans. Squaramides and polyamine derivatives have been demonstrated to have antitumor and antiprotozoal activity. The aim of this study was to investigate the activity of 5 squaramides and 5 acyclic polyamines against trophozoites and cysts of A. castellanii Neff. Amoebicidal activity against the trophozoites and cytotoxicity against Vero cells were evaluated with a colorimetric assay, using Alamar Blue?, and chlorhexidine digluconate was assayed as the reference drug. The squaramides 3 and 5 and the acyclic polyamine 6 appeared to be the most active against the trophozoites and their cytotoxicity was low, showing selectivity indexes of 28.3, 26, and 25.7, respectively, similar to the control drug, chlorhexidine digluconate (27.6). But only the squaramide 3 showed complete cysticidal activity at the concentrations of 100 and 200 μM, as the chlorhexidine digluconate. Further studies of the mechanism of action and in vivo assays are needed, but squaramide 3 could be used for developing novel therapeutic approaches against Acanthamoeba infections.
基金the Spanish MINECO(projects RTI2018-095622-B-I00,RTI2018-095038-B-I00)the Catalan AGAUR(project 2017 SGR 238)+1 种基金the ERC under the EU FP7(ER C-Co 615954)European Unions Horizon 2020 research and innovation program under grant agreement No.685727,and European Structural Funds(S2018/NMT-4367).It was alsofunded by the CERCA Program/Generalitat de Catalunya.ICN2 is supported by the Severo Ochoa program from the Spanish MINECO(G rant No.SEV-2017-0706).
文摘A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic centers.Here,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic transformations.These programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SNU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide centers.Squaramides were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching phenomena.Therefore,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore environments.We then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide ring-opening.Some of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.
基金support from the Na-tional Natural Science Foundation of China(Grant No.21272024).
文摘Enantioselective synthesis of biologically active dihydropyrano[2,3-c]pyrazoles has been achieved through a squaramide-catalysed Michael addition/Thorpe-Ziegler type cyclization cascade reaction between arylidenepyra-zolones and malononitrile.A series of optically active dihydropyano[2,3-c]pyrazoles were obtained in excellent yields(up to 99%)and moderate to good enantioselectivities(up to 79%ee)under mild reaction conditions.
基金Financial support received from NSFC(Nos.21704048,22031005)the Department of Science and Technology of Shandong Province(No.ZR2020LFG014)the Taishan Scholars Constructive Engineering Foundation(No.tsqn20161031)is gratefully acknowledged.
文摘Substa ntial progresses have bee n made toward the developme nt of meta I-free catalysts for stereoselective rin g-ope ning polymeriza-tion(ROP)of rac-lactide.Yet the discovery of organic catalysts effective at ambient temperature remains a major challenge.Here,the bifunctional H-bonding catalyst SQ-1 containing a basic tertiary amine and squaramide motif proved to be good candidate for the stereoselective ROP of rac-lactide at room temperature,yielding stereoregular polylactide with controlled molecular weights(up to 21.1 kg/mol)and high tacticity(PjESC up to 0.88).Furthermore,binary H-b on ding catalytic system con sisti ng of squaramides(SQ-2 to SQ-6)and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)could efficiently promote the ROP of rac-lactide at room temperature within short reaction time.Among them,the most bulky squaramide SQ-2 exhibited the best steroselectivity towards the ROP of rac-lactide without transesterification side reactions during the polymerization process.The resulting polylactides were proved to have controlled molecular weights as high as 22.2 kg/mol and narrow distributions(1.10-1.24).
基金We are grateful for financial support from the National Natural Science Foundation of China(Grant No.21272024).
文摘An efficient enantioselective cascade sulfa-Michael/Michael addition reaction of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl ester with nitroalkenes catalyzed by a chiral squaramide catalyst was disclosed.This cascade reaction afforded thiochroman derivatives with three contiguous stereocenters in high yields(up to 94%),excellent diastereoselectivities(up to>25∶1 dr)and enantioselectivities(up to 99% ee).
基金Project supported by the National Natural Science Foundation of China(No.51403053)the University Scientific Innovation Team of Henan Province(No.24IRTSTHN017)。
文摘Isosteviol,the hydrolysate of stevioside,has attracted increasing attention from scientists because of its special molecular skeleton and extensive biological activities.In recent years,due to the continuous rise of organocatalysis,an increasing number of organocatalysts based on isosteviol have been devised and synthesized to facilitate a range of highly enantioselective asymmetric synthesis.The isosteviol-type organocatalysts reported in the literature over the past decade and their applications in asymmetric catalysis are systematically analyzed and elaborated in order to provide assistance for the further design,synthesis,and application of organocatalysis derived from isosteviol.
基金support from National Natural Science Foundation of China(22371265,22201266)Natural Science Foundation of Henan Province(232301420047)the project of State Key Laboratory of Green Pesticide,Guizhou Medical University(GPLKF202507).
文摘A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activation of 3-aminophenol derivatives and 4-benzylidenepyrrolidine-2,3-diones by the chiral catalyst,enabling an efficient asymmetric oxa-[3+3]-annulation reaction.The protocol exhibits a broad substrate scope with 34 diverse examples,delivering moderate-to-good yields ranging from 64%to 81%,excellent enantioselectivity(up to 99%ee),and tunable diastereoselectivity(dr up to 15:1).Notably,halogen substitution plays a pivotal role in dramatically enhancing stereocontrol,further optimizing the diastereoselectivity of the target products.To validate its practical utility,gram-scale synthesis was successfully conducted without compromising yield or stereoselectivity,and subsequent derivatization reactions confirmed the versatility of the obtained chiral tricyclic chromans.This metal-free,mild reaction system not only enriches the synthetic toolbox for constructing complex chroman architectures,but also provides a versatile platform for the asymmetric synthesis of bioactive molecules containing the chiral tricyclic chroman skeleton,highlighting the significance of enantioselectivity and diastereoselectivity in accessing functionalized heterocyclic compounds.
文摘The saccharide-based chiral bifunctional thiourea-phosphines were developed as chiral organocatalysts for the intramolecular Morita-Baylis-Hillman reaction of o^-formyl-enones. With only 2 tool% of thiourea-phosphine cata- lyst 3c, chiral functionalized cyclohexenes were achieved under mild reaction conditions with excellent yields and enantioselectivities.
