To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins […]
Dianrong Li#, Chao Li#, Lin Li, She Chen, Lei Wang, Qiang Li, Xiaodong Wang, Xiaoguang Lei* and Zhirong Shen*
Cell Chemical Biology 2016, 23, 257-266
Highlights ?Kongensin A (KA) is a potent inhibitor of necroptosis and an inducer of apoptosis ?KA inhibits necroptosis by preventing the activation of RIPK3 ?TQ ligation enables the identification of HSP90 as a cellular target of KA ?KA covalently binds to HSP90 and inhibits HSP90 through a novel mode of action Summary RIP3-dependent necroptosis […]
We report our synthetic studies towards the synthesis of the C3-C14 fragment of alchivemycin A. The synthesis featured an asymmetric alkylation with excellent diastereoselectivity and a one-pot Julia-Kocienski olefination with excellent E-selectivity. Intramolecular Diels-Alder reaction was employed to construct the highly functionalized cis-decalin framework. Interestingly, the stereochemical outcome was unexpected to generate two stereoisomers 20 […]
Lei Gao, Jianguang Han, and Xiaoguang Lei*
Org. Lett. 2016, 18, 360-363
ABSTRACT: The first enantioselective total syntheses of?(?)-kuwanon X, (+)-kuwanon Y, and (+)-kuwanol A have been accomplished by using asymmetric Diels?Alder cycloaddition promoted by chiral VANOL or VAPOL/boron Lewis acid. The biosynthesis-inspired asymmetric Diels?Alder cycloaddition shows high exo selectivity (exo/endo = 13/1), which was unprecedented in the previous total syntheses of related prenylflavonoid Diels?Alder natural products. […]
Abstract:We report the first scalable synthesis of rac-jungermannenones B (1) and C (2) starting from commercially available inexpensive geraniol (8) in 10 and 9 steps, respectively. The unique jungermannenone framework is rapidly assembled by an unprecedented regioselective 1, 6-dienyne reductive cyclization reaction which proceeds via a vinyl radical cyclization-allylic radical isomerization mechanism. DFT calculations explain […]
Abstract The use of chemoprotective agents to minimize the side effects of the chemotherapy, primarily via activation of the Nrf2 pathway, is an emerging research field, which has attracted broad attention from both academia and pharmaceutical industry. Through high-throughput chemical screens we have disclosed that pterisolic acid B (J19), a naturally occuring diterpenoid, is an […]
ABSTRACT An efficient method for the asymmetric Diels-Alder cycloaddition of 2’-hydroxychalcones with acyclic or cyclic dienes has been successfully developed. The Diels-Alder cycloaddition is mediated by a chiral boron complex with VANOL, affording the corresponding products in high yields and with excellent diastereo- and enantio-selectivities. This reaction enabled the enantioselective construction of cyclohexene skeletons crucial […]
Abstract: The increase and spread of Gram-negative bacteria resistant to almost all currently available β-lactam antibiotics is a major global health problem. The cause for drug resistance is primarily due to the acquisition of metallo-β-lactamases such as NDM-1. Aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in […]
Shaoqiang Yang, Daohong Liao,Xiaoqi Tian, and Xiaoguang Lei*
Org. Lett. 2016, 18, 376-379
Abstract: A general and efficient synthesis of the 2H-tetrahydro-4,6-dioxo-1,2-oxazine ring system through a tandem nucleophilic addition and transesterification reaction is described. The reaction is highly functional-group-tolerant and proceeds under mild conditions, affording the corresponding products in good to excellent yields. This method represents the first general synthetic route to access this heterocyclic scaffold, which exists […]
Ting Dong, Daohong Liao, Xiaohui Liu, and Xiaoguang Lei
ChemBioChem 2015, 16, 2557-2561
Abstract Genetically programmed cell death is a universal and fundamental cellular process in multicellular organisms. Apoptosis and necroptosis, two common forms of programmed cell death, play vital roles in maintenance of homeostasis in metazoans. Dysfunction of the regulatory machinery of these processes can lead to carcinogenesis or autoimmune diseases. Inappropriate death of essential cells can […]
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Trifunctional Cross-Linker for Mapping Protein-Protein Interaction Networks and Comparing Protein Conformational States
Tan, D.; Li, Q.; Zhang, M.; Liu, C.; Ma, C.; Zhang, P.; Ding, Y.; Fan, S.; Tao, L.; Yang, B.; Li, X.; Ma, S.; Liu, J.; Feng, B.; Liu, X.; Wang, H.; He, S.; Gao, N.; Ye, K.; Dong, M.*; Lei, X.*
eLife 2016; 5:e12509
To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins […]
Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis
Dianrong Li#, Chao Li#, Lin Li, She Chen, Lei Wang, Qiang Li, Xiaodong Wang, Xiaoguang Lei* and Zhirong Shen*
Cell Chemical Biology 2016, 23, 257-266
Highlights ?Kongensin A (KA) is a potent inhibitor of necroptosis and an inducer of apoptosis ?KA inhibits necroptosis by preventing the activation of RIPK3 ?TQ ligation enables the identification of HSP90 as a cellular target of KA ?KA covalently binds to HSP90 and inhibits HSP90 through a novel mode of action Summary RIP3-dependent necroptosis […]
Studies towards the Synthesis of the Functionalized C3-C14 Decalin Framework of Alchivemycin A
Ma, K.; Liao, D.; Yang, S.; Li, X.; Lei, X.*
Org. Chem. Front. 2016, 3, 251-258
We report our synthetic studies towards the synthesis of the C3-C14 fragment of alchivemycin A. The synthesis featured an asymmetric alkylation with excellent diastereoselectivity and a one-pot Julia-Kocienski olefination with excellent E-selectivity. Intramolecular Diels-Alder reaction was employed to construct the highly functionalized cis-decalin framework. Interestingly, the stereochemical outcome was unexpected to generate two stereoisomers 20 […]
Enantioselective Total Syntheses of Kuwanon X, Kuwanon Y and Kuwanol A
Lei Gao, Jianguang Han, and Xiaoguang Lei*
Org. Lett. 2016, 18, 360-363
ABSTRACT: The first enantioselective total syntheses of?(?)-kuwanon X, (+)-kuwanon Y, and (+)-kuwanol A have been accomplished by using asymmetric Diels?Alder cycloaddition promoted by chiral VANOL or VAPOL/boron Lewis acid. The biosynthesis-inspired asymmetric Diels?Alder cycloaddition shows high exo selectivity (exo/endo = 13/1), which was unprecedented in the previous total syntheses of related prenylflavonoid Diels?Alder natural products. […]
Scalable Total Synthesis of Jungermannenones B and C
Weilong Liu, Houhua Li, Peijun Cai, Zhen Wang, Zhi-Xiang Yu, and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2016, 55, 3112-3116
Abstract:We report the first scalable synthesis of rac-jungermannenones B (1) and C (2) starting from commercially available inexpensive geraniol (8) in 10 and 9 steps, respectively. The unique jungermannenone framework is rapidly assembled by an unprecedented regioselective 1, 6-dienyne reductive cyclization reaction which proceeds via a vinyl radical cyclization-allylic radical isomerization mechanism. DFT calculations explain […]
Pterisolic Acid B is a Nrf2 Activator by Targeting C171 within Keap1-BTB Domain
Dong, T.; Liu, W.; Shen, Z.; Li, L.; Chen, S.; Lei, X.*
Scientific Reports 2016, 6, 19231
Abstract The use of chemoprotective agents to minimize the side effects of the chemotherapy, primarily via activation of the Nrf2 pathway, is an emerging research field, which has attracted broad attention from both academia and pharmaceutical industry. Through high-throughput chemical screens we have disclosed that pterisolic acid B (J19), a naturally occuring diterpenoid, is an […]
Chiral Boron Complex-Promoted Asymmetric Diels-Alder Cycloaddition and Its Application in Natural Product Synthesis
Li, X.; Han, J.; Jones, A.; Lei, X.*
J. Org. Chem. 2016, 81, 458-468
ABSTRACT An efficient method for the asymmetric Diels-Alder cycloaddition of 2’-hydroxychalcones with acyclic or cyclic dienes has been successfully developed. The Diels-Alder cycloaddition is mediated by a chiral boron complex with VANOL, affording the corresponding products in high yields and with excellent diastereo- and enantio-selectivities. This reaction enabled the enantioselective construction of cyclohexene skeletons crucial […]
Total Synthesis and Structural Reassignment of Aspergillomarasmine A
Liao, D.; Yang, S.; Wang, J.; Zhang, J. Hong, B.; Wu, F.; Lei, X.*
Angew. Chem. Int. Ed. 2016, 55, 4291-4295
Abstract: The increase and spread of Gram-negative bacteria resistant to almost all currently available β-lactam antibiotics is a major global health problem. The cause for drug resistance is primarily due to the acquisition of metallo-β-lactamases such as NDM-1. Aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in […]
Access to the 2H-Tetrahydro-4,6-dioxo-1,2-oxazine Ring System from Nitrone via a Tandem Nucleophilic Addition and Transesterification Reaction
Shaoqiang Yang, Daohong Liao,Xiaoqi Tian, and Xiaoguang Lei*
Org. Lett. 2016, 18, 376-379
Abstract: A general and efficient synthesis of the 2H-tetrahydro-4,6-dioxo-1,2-oxazine ring system through a tandem nucleophilic addition and transesterification reaction is described. The reaction is highly functional-group-tolerant and proceeds under mild conditions, affording the corresponding products in good to excellent yields. This method represents the first general synthetic route to access this heterocyclic scaffold, which exists […]
Using Small Molecules to Dissect Non-apoptotic Programmed Cell Death: Necroptosis, Ferroptosis, and Pyroptosis
Ting Dong, Daohong Liao, Xiaohui Liu, and Xiaoguang Lei
ChemBioChem 2015, 16, 2557-2561
Abstract Genetically programmed cell death is a universal and fundamental cellular process in multicellular organisms. Apoptosis and necroptosis, two common forms of programmed cell death, play vital roles in maintenance of homeostasis in metazoans. Dysfunction of the regulatory machinery of these processes can lead to carcinogenesis or autoimmune diseases. Inappropriate death of essential cells can […]