The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellari...The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl （TIPS）-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-lH-pyrrole, was obtained through desilylation of 3,4-disubstituent-l-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-lH-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic com- pounds, permethylated derivatives ofneolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.展开更多
Natural product elansolid A belongs to one type of polyketide macrolactone with promising antibiotic activity.Pre-viously,the first total synthesis of elansolid A in 28 longest linear sequence(LLS)and 41 steps in tota...Natural product elansolid A belongs to one type of polyketide macrolactone with promising antibiotic activity.Pre-viously,the first total synthesis of elansolid A in 28 longest linear sequence(LLS)and 41 steps in total has been achieved.Herein,the simplified analog of elansolid A,featured with a cyclohexyl-fused 19-memebered macrolactone,was proposed,and its asymmetric total synthesis based on a convergent strategy and key reactions exemplified by desymmetric alcoholysis of anhydride,Pd-catalyzed Stille coupling,Suzuki-Miyaura coupling as well as Mukaiyama macrolactonization was finished.展开更多
Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthes...Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthesize the heterocyclic compounds,based on the patterns of bond formation during the construction of the heterocyclic backbones.展开更多
A controllable diastereoselective C(sp2)-C(sp3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides has been demonstrated for the first time, forming medicinally important 1-arylphenylethy...A controllable diastereoselective C(sp2)-C(sp3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides has been demonstrated for the first time, forming medicinally important 1-arylphenylethylamines. In the presence of Pd(OAc) 2 and S-phos, open-chain (2-amido-1-phenylethyl)zinc reagents bearing a -NHAc or NHCHO group underwent cross-coupling reaction to give syn 1-arylphenylethylamine as the major products, whereas the zinc reagents bearing a sterically hindered-NHCOC(CH3)2 OTBS group specifically yielded anti 1-arylphenylethylamines.展开更多
Combining the stability of chemical crosslinking and the processability of physical crosslinking is a well-established strategy to design new materials with desirable stimuli–responsive properties. Herein, a series o...Combining the stability of chemical crosslinking and the processability of physical crosslinking is a well-established strategy to design new materials with desirable stimuli–responsive properties. Herein, a series of azobenzenebased thermotropic liquid crystalline polyesters were synthesized by introducing mesogenic dial named 4,4＇-bis（6-hydroxyhexyloxy）azobenzene（BHHAB）, 2-phenylsuccinic acid（PSA）, and different contents of 1,2,3-propanetricarboxylic acid（PTA） as the chemical crosslinker. All these polyesters showed good thermal stability and smectic liquid crystalline phase. Wide-angel X-ray diffraction（WAXD） and the fluorescence emission spectra confirmed the existence of π–πstacking interactions as the physical crosslinking in the polymer chains, particularly at the lower content of PTA. However, when the PTA content increased, the chemical crosslinking changed the chain conformation, and thus the intensity of physical crosslinking slackened gradually. Combining the physical and chemical crosslinking, these polyesters showed the thermoplastic processability, thermal shape memory, heat-assisted healing and photoresponsive behaviors. Taking advantages of these features, these multiple stimuli–responsive polymers can bring more chances for smart materials such as soft actuator.展开更多
The G-protein coupled receptors(GPCRs)play fundamental roles in the human biololgy and drug discovery.GPCRs function as signalling molecules that transduce extracellular signals into cells.The signalling transduction ...The G-protein coupled receptors(GPCRs)play fundamental roles in the human biololgy and drug discovery.GPCRs function as signalling molecules that transduce extracellular signals into cells.The signalling transduction is generally triggered by interacting with ligands,including photons,ions,small organic compounds,peptides,proteins and lipids.In this review,we focus on interactions with diffusible ligands such as hormones and neurotransmitters.We discuss three aspects of the complexity of the GPCR-ligand interactions:functional selectivity of ligands,receptor subtype selectivity of ligands and orphan GPCRs.展开更多
Porous polymer supported palladium catalyst for cross coupling reactions with high activity has been successfully prepared by coordination of Pd 2+ species with Schiff bases functionalized porous polymer. The catalyst...Porous polymer supported palladium catalyst for cross coupling reactions with high activity has been successfully prepared by coordination of Pd 2+ species with Schiff bases functionalized porous polymer. The catalyst has been systemically investi-gated by a series of characterizations such as TEM, N 2 adsorption, NMR, IR, XPS, etc. TEM and N 2 isotherms show that the sample maintains the nanoporous structure after the modification and coordination. XPS results show that chemical state of palladium species in the catalyst is mainly +2. More importantly, the catalyst shows very high activities and excellent recycla-bility in a series of coupling reactions including Suzuki, Sonogashira, and Heck reactions. Hot filtration and poison of catalysts experiments have also been performed and the results indicate that soluble active species (mainly Pd(0) species) in-situ gener-ated from the catalyst under the reaction conditions are the active intermediates, which would redeposit to the supporter after the reactions.展开更多
基金supported by the National Natural Science Foundation of China (21171154 and 91129706)Special Fund for Marine Scientific Research in the Public Interest (01005024)
文摘The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl （TIPS）-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-lH-pyrrole, was obtained through desilylation of 3,4-disubstituent-l-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-lH-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic com- pounds, permethylated derivatives ofneolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.
基金Project supported by the High-Level Talent Program of Yunnan Province(No.Y93D321261)the Regional Development Program for Young Scholars,Chinese Academy of Sciences(CAS)(No.E323521311)the Science and Technology Department of Yunan Province(Nos.202305AH34005,202401AS070096)。
文摘Natural product elansolid A belongs to one type of polyketide macrolactone with promising antibiotic activity.Pre-viously,the first total synthesis of elansolid A in 28 longest linear sequence(LLS)and 41 steps in total has been achieved.Herein,the simplified analog of elansolid A,featured with a cyclohexyl-fused 19-memebered macrolactone,was proposed,and its asymmetric total synthesis based on a convergent strategy and key reactions exemplified by desymmetric alcoholysis of anhydride,Pd-catalyzed Stille coupling,Suzuki-Miyaura coupling as well as Mukaiyama macrolactonization was finished.
基金the National Natural Science Foundation of China(21072148)Foundation(B)for Peiyang Scholar-Young Core Faculty of Tianjin University(2013XR-0144)the Innovation Foundation of Tianjin University(2013XJ-0005)for financial support
文摘Hypervalent iodine(Ⅲ)reagents have been vastly used in many useful organic transformations.In this review article,we highlight the strategies that used the common hypervalent iodine(Ⅲ)reagents as oxidants to synthesize the heterocyclic compounds,based on the patterns of bond formation during the construction of the heterocyclic backbones.
基金the National Natural Science Foundation of China (21172227)Jishou University (2012)
文摘A controllable diastereoselective C(sp2)-C(sp3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides has been demonstrated for the first time, forming medicinally important 1-arylphenylethylamines. In the presence of Pd(OAc) 2 and S-phos, open-chain (2-amido-1-phenylethyl)zinc reagents bearing a -NHAc or NHCHO group underwent cross-coupling reaction to give syn 1-arylphenylethylamine as the major products, whereas the zinc reagents bearing a sterically hindered-NHCOC(CH3)2 OTBS group specifically yielded anti 1-arylphenylethylamines.
基金supported by the National Natural Science Foundation of China (51721091)the Sichuan Province Youth Science and Technology Innovation Team (2017TD0006)
文摘Combining the stability of chemical crosslinking and the processability of physical crosslinking is a well-established strategy to design new materials with desirable stimuli–responsive properties. Herein, a series of azobenzenebased thermotropic liquid crystalline polyesters were synthesized by introducing mesogenic dial named 4,4＇-bis（6-hydroxyhexyloxy）azobenzene（BHHAB）, 2-phenylsuccinic acid（PSA）, and different contents of 1,2,3-propanetricarboxylic acid（PTA） as the chemical crosslinker. All these polyesters showed good thermal stability and smectic liquid crystalline phase. Wide-angel X-ray diffraction（WAXD） and the fluorescence emission spectra confirmed the existence of π–πstacking interactions as the physical crosslinking in the polymer chains, particularly at the lower content of PTA. However, when the PTA content increased, the chemical crosslinking changed the chain conformation, and thus the intensity of physical crosslinking slackened gradually. Combining the physical and chemical crosslinking, these polyesters showed the thermoplastic processability, thermal shape memory, heat-assisted healing and photoresponsive behaviors. Taking advantages of these features, these multiple stimuli–responsive polymers can bring more chances for smart materials such as soft actuator.
基金supported in part bythe National Institutes of Health(GM67168 to Dr.Yong Duan)computing resources at the National Supercomputing Center TeraGrid(MCB100132 to Dr.Ting Wang and MCA06N028 to Dr.Yong Duan)
文摘The G-protein coupled receptors(GPCRs)play fundamental roles in the human biololgy and drug discovery.GPCRs function as signalling molecules that transduce extracellular signals into cells.The signalling transduction is generally triggered by interacting with ligands,including photons,ions,small organic compounds,peptides,proteins and lipids.In this review,we focus on interactions with diffusible ligands such as hormones and neurotransmitters.We discuss three aspects of the complexity of the GPCR-ligand interactions:functional selectivity of ligands,receptor subtype selectivity of ligands and orphan GPCRs.
基金supported by the National Natural Science Foundation of China (20973079 & 21003107)State Basic Research Project of China(2009CB623507)Fundamental Research Funds for the Central Universities (2010QNA3035)
文摘Porous polymer supported palladium catalyst for cross coupling reactions with high activity has been successfully prepared by coordination of Pd 2+ species with Schiff bases functionalized porous polymer. The catalyst has been systemically investi-gated by a series of characterizations such as TEM, N 2 adsorption, NMR, IR, XPS, etc. TEM and N 2 isotherms show that the sample maintains the nanoporous structure after the modification and coordination. XPS results show that chemical state of palladium species in the catalyst is mainly +2. More importantly, the catalyst shows very high activities and excellent recycla-bility in a series of coupling reactions including Suzuki, Sonogashira, and Heck reactions. Hot filtration and poison of catalysts experiments have also been performed and the results indicate that soluble active species (mainly Pd(0) species) in-situ gener-ated from the catalyst under the reaction conditions are the active intermediates, which would redeposit to the supporter after the reactions.
