Wang, G.; Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.* ; Wang, X. *
Nat. Chem. Biol. 2013, 9, 84-89. ( News stories describing this work were highlighted in Chem. & Eng. News 2013 , 2 , 37 ; Nature Asia 2012 , December 24)
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand ( TRAIL ) activates apoptosis through the death receptors DR4 and DR5 . Because of its superior safety profile and high tumor specificity compared to other TNF family members, recombinant soluble TRAIL and agonistic antibodies against its receptors are actively being developed for clinical cancer therapy. Here, we describe […]
Houhua Li, Xiaoming Wang, Benke Hong and Xiaoguang Lei*
J. Org. Chem. 2013, 78, 800-821 Featured and Cover Article
The collective total synthesis of?Lycopodium?alkaloids (+)-fawcettimine, (+)-fawcettidine, (+)-alopecuridine, (-)-lycojapodine A, and (-)-8-deoxyserratinine has been accomplished from a common precursor based on a highly concise route inspired by the proposed biosynthesis of the fawcettimine- and serratinine-type alkaloids. An intramolecular?C?-alkylation enabled efficient installation of the challenging spiro quaternary carbon center and the […]
Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.; Lei, X.* ; Wang, X. *
Cell 2012, 148, 213-227 (News stories describing this work were highlighted in Chem. & Eng. News 2012 , 5 , 40 ; Nature China 2012 , February 1; Asian Scientist 2012 , January31; and Nature Reviews Molecular Cell Biology , 2012, Feb. 8)
The receptor-interacting serine-threonine kinase 3 (RIP3) is a key signaling molecule in the programmed necrosis (necroptosis) pathway. This pathway plays important roles in a variety of physiological and pathological conditions, including development, tissue damage response, and antiviral immunity. Here, we report the identification of a small molecule called (E)-?N?-(4-(?N?-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide?-hereafter referred to as necrosulfonamide?-that specifically blocks […]
Houhua Li, Xiaoming Wang and Xiaoguang Lei*
Angew. Chem. Int. Ed . 2012, 51, 491-495; Angew. Chem . 2012 , 124 , 506-510
Drei?Lycopodium-Alkaloide vom Fawcettimin- und Serratinin-Typ wurden ausgehend von einem gemeinsamen tetracyclischen Spirodiketon-Intermediat in kurzen Totalsynthesen hergestellt (siehe Schema). Das Intermediat selbst wurde über eine Biosynthese-inspirierte transannulare N-C-Knüpfung zum spirokonfigurierten Kohlenstoffzentrum und eine Hydroxy-gelenkte SmI2-vermittelte View Full Article
Daohong Liao, Houhua Li and Xiaoguang Lei*
Org. Lett. 2012, 14, 18-21
An efficient method using silver oxide-mediated oxidation for the synthesis of?ortho-quinone methides has been developed and applied to the biomimetic syntheses of novel trimeric natural products, (±)-schefflone and tocopherol trimers. Further studies of the critical trimerization as well as substrate scope and limitations are also reported. View Full Article
Ting-Chao Chou, Huajin Dong, Xiuguo Zhang, Xiaoguang Lei, John Hartung, Yandong Zhang, Jun Hee Lee, Rebecca M. Wilson, and Samuel J. Danishefsky
PNAS 2011, 108, 14336-1434
We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found […]
Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors (TLRs) recognize pathogen-derived products and induce NF-κB-dependent pro-IL-1β transcription; NOD-like receptors (NLRs) assemble caspase-1-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specific and potent inhibitor of the caspase-1 pathway. Bromoxone […]
Chao Li, Xueliang Yu and Xiaoguang Lei*
Org. Lett. 2010, 12, 4284-4287
A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has been accomplished in 14 steps from α-santonin. The synthesis relies on a hydrogen bonding promoted [4 + 2]-hetero-Diels?Alder dimerization to afford the key homodimer intermediate, which demonstrates the feasibility of using nonenzymatic conditions to achieve the proposed biosynthesis.
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Small Molecule Activation of the TRAIL Receptor DR5 in Human Cancer Cells
Wang, G.; Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.* ; Wang, X. *
Nat. Chem. Biol. 2013, 9, 84-89. ( News stories describing this work were highlighted in Chem. & Eng. News 2013 , 2 , 37 ; Nature Asia 2012 , December 24)
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand ( TRAIL ) activates apoptosis through the death receptors DR4 and DR5 . Because of its superior safety profile and high tumor specificity compared to other TNF family members, recombinant soluble TRAIL and agonistic antibodies against its receptors are actively being developed for clinical cancer therapy. Here, we describe […]
Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of ( – )-Lycojapodine A
Houhua Li, Xiaoming Wang, Benke Hong and Xiaoguang Lei*
J. Org. Chem. 2013, 78, 800-821 Featured and Cover Article
The collective total synthesis of?Lycopodium?alkaloids (+)-fawcettimine, (+)-fawcettidine, (+)-alopecuridine, (-)-lycojapodine A, and (-)-8-deoxyserratinine has been accomplished from a common precursor based on a highly concise route inspired by the proposed biosynthesis of the fawcettimine- and serratinine-type alkaloids. An intramolecular?C?-alkylation enabled efficient installation of the challenging spiro quaternary carbon center and the […]
Biomimetic Syntheses of (-)-Gochnatiolides A-C and (-)-Ainsliadimer B
Chao Li, Longyang Dian, Weidong Zhang, and Xiaoguang Lei*
J. Am. Chem. Soc. 2012, 134, 12414-12417
We report the first biomimetic syntheses of (
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.; Lei, X.* ; Wang, X. *
Cell 2012, 148, 213-227 (News stories describing this work were highlighted in Chem. & Eng. News 2012 , 5 , 40 ; Nature China 2012 , February 1; Asian Scientist 2012 , January31; and Nature Reviews Molecular Cell Biology , 2012, Feb. 8)
The receptor-interacting serine-threonine kinase 3 (RIP3) is a key signaling molecule in the programmed necrosis (necroptosis) pathway. This pathway plays important roles in a variety of physiological and pathological conditions, including development, tissue damage response, and antiviral immunity. Here, we report the identification of a small molecule called (E)-?N?-(4-(?N?-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide?-hereafter referred to as necrosulfonamide?-that specifically blocks […]
Total Syntheses of Lycopodium Alkaloids (+)-Fawcettimine, (+)-Fawcettidine, and (-)-8-Deoxyserratinine
Houhua Li, Xiaoming Wang and Xiaoguang Lei*
Angew. Chem. Int. Ed . 2012, 51, 491-495; Angew. Chem . 2012 , 124 , 506-510
Drei?Lycopodium-Alkaloide vom Fawcettimin- und Serratinin-Typ wurden ausgehend von einem gemeinsamen tetracyclischen Spirodiketon-Intermediat in kurzen Totalsynthesen hergestellt (siehe Schema). Das Intermediat selbst wurde über eine Biosynthese-inspirierte transannulare N-C-Knüpfung zum spirokonfigurierten Kohlenstoffzentrum und eine Hydroxy-gelenkte SmI2-vermittelte View Full Article
Efficient Generation of ortho -Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers
Daohong Liao, Houhua Li and Xiaoguang Lei*
Org. Lett. 2012, 14, 18-21
An efficient method using silver oxide-mediated oxidation for the synthesis of?ortho-quinone methides has been developed and applied to the biomimetic syntheses of novel trimeric natural products, (±)-schefflone and tocopherol trimers. Further studies of the critical trimerization as well as substrate scope and limitations are also reported. View Full Article
Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol
Ting-Chao Chou, Huajin Dong, Xiuguo Zhang, Xiaoguang Lei, John Hartung, Yandong Zhang, Jun Hee Lee, Rebecca M. Wilson, and Samuel J. Danishefsky
PNAS 2011, 108, 14336-1434
We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found […]
Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C
Chao Li , Shanghui Tu, Shuguang Wen, Shan Li, Junbo Chang, Feng Shao, Xiaoguang Lei*
J. Org. Chem. 2011, 76, 3566-3570
View Full Article
Chemical Probing reaveals insights into the signaling mechanism of inflammasome activation
Yi-Nan Gong, Xiaoming Wang, Jiayi Wang, Zhenxiao Yang, Shan Li, Jieling Yang, Liping Liu, Xiaoguang Lei* and Feng Sh
Cell. Res. 2010, 20, 1289-1305
Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors (TLRs) recognize pathogen-derived products and induce NF-κB-dependent pro-IL-1β transcription; NOD-like receptors (NLRs) assemble caspase-1-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specific and potent inhibitor of the caspase-1 pathway. Bromoxone […]
A Biomimetic Total Synthesis of (+)-Ainsliadimer A
Chao Li, Xueliang Yu and Xiaoguang Lei*
Org. Lett. 2010, 12, 4284-4287
A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has been accomplished in 14 steps from α-santonin. The synthesis relies on a hydrogen bonding promoted [4 + 2]-hetero-Diels?Alder dimerization to afford the key homodimer intermediate, which demonstrates the feasibility of using nonenzymatic conditions to achieve the proposed biosynthesis.