Natural products continue to provide a rich source of inspiration for both chemists and biologists. The efficient synthesis of bioactive natural products or natural product-like molecules has offered tremendous opportunities for complex biological processes exploration and drug discovery. However, because natural products usually contain numerous stereogenic centres and polycyclic ring systems, significant synthetic challenges remain. […]
Jianguang Han, Xia Li, Yong Guan, Wenjun Zhao, William D. Wulff * and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2014, 53, 9257-9261
The first enantioselective total syntheses of prenylflavonoid Diels-Alder natural products (-)-kuwanon I, (+)-kuwanon J, (-)-brosimone A and (-)-brosimone B have been accomplished based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis-inspired asymmetric Diels-Alder cycloaddition mediated by a chiral VANOL-boron Lewis acid, as well as a process involving regioselective Schenck ene […]
Chao Li and Xiaoguang Lei*
J. Org. Chem. 2014, 79, 3289-3295
Congratulations on?Chao’s latest JOCSynopsis paper! Abstract: Oligomeric sesquiterpenoids, biogenetically assembled from two or three monomeric sesquiterpenoid units via diverse pathways, represent a unique class of natural products. The synthetic studies inspired by their biogenesis have offered significant impetus for the efficient construction of these architecturally complex frameworks. Here we provide an overview for the biomimetic […]
Daohong Liao, Liming Sun, Weilong Liu, Sudan He, Xiaodong Wang and Xiaoguang Lei*
Med. Chem. Commun., 2014,5, 333-337
Abstract: Through high-throughput screening of 200000 compounds and subsequent structure–activity relationship (SAR) studies we identified necrosulfonamide (NSA) as a potent small molecule inhibitor for necroptosis, induced by a combination of TNF-a, Smac mimetic, and z-VAD-fmk (T/S/Z). Applying a forward chemical genetic approach, we utilized an NSA based chemical probe to further reveal that NSA selectively […]
ABSTRACT: Bioorthogonal ligations have found widespread use in biomedical research for site selective labeling of biomolecules in living systems. Discovering new reactions to expand the toolbox of bioorthogonal chemistry remains an important, yet challenging, task as most reactions do not meet the stringent requirements of bioorthogonal reaction. As highly useful synthetic intermediates, ortho-quinone methides (oQMs) […]
The fawcettimine- and serratinine-type lycopodium alkaloids are a series of structurally complex but related natural products. These alkaloids have been the subjects of intense studies by the synthetic chemistry community, and many elegant strategies have been developed. Herein, we describe the recently disclosed synthetic strategies towards this unique family of natural products, in particular the […]
Li, Q.; Dong, T.; Liu, X.; Lei, X.*
J. Am. Chem. Soc. 2013 , 135 , 4996-4999 . ( News story describing this work was highlighted in Chem. & Eng. News 2013 , 14 , 37 ).
There is an increasing interest in the use of bioorthogonal ligation to advance biomedical research through selective labeling of biomolecules in living systems. Accordingly, discovering new reactions to expand the toolbox of bioorthogonal chemistry is of particular interest to chemical biologists. Herein we report a new bioorthogonal ligation enabled by click hetero-Diels–Alder (HDA) cycloaddition […]
Ainsliatrimers A and B are two recently isolated complex sesquiterpenoid natural products that display the unprecedented chemical motifs and remarkable anti-cancer activities. The exact structures as well as the mechanism of anti-cancer action for ainsliatrimers A and B remain to be elucidated. Here we report the first concise and biomimetic syntheses of (-)-ainsliatrimers A and […]
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 […]
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Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern
Jing Zhang, Jinbao Wu, Benke Hong, Wenying Ai, Xiaoming Wang, Houhua Li & Xiaoguang Lei*
Nat. Commun. 2014, 5, 4614
Natural products continue to provide a rich source of inspiration for both chemists and biologists. The efficient synthesis of bioactive natural products or natural product-like molecules has offered tremendous opportunities for complex biological processes exploration and drug discovery. However, because natural products usually contain numerous stereogenic centres and polycyclic ring systems, significant synthetic challenges remain. […]
Enantioselective Biomimetic Total Syntheses of Kuwanons I and J and Brosimones A and B
Jianguang Han, Xia Li, Yong Guan, Wenjun Zhao, William D. Wulff * and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2014, 53, 9257-9261
The first enantioselective total syntheses of prenylflavonoid Diels-Alder natural products (-)-kuwanon I, (+)-kuwanon J, (-)-brosimone A and (-)-brosimone B have been accomplished based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis-inspired asymmetric Diels-Alder cycloaddition mediated by a chiral VANOL-boron Lewis acid, as well as a process involving regioselective Schenck ene […]
Strategies towards the Biomimetic Syntheses of Oligomeric Sesquiterpenoids
Chao Li and Xiaoguang Lei*
J. Org. Chem. 2014, 79, 3289-3295
Congratulations on?Chao’s latest JOCSynopsis paper! Abstract: Oligomeric sesquiterpenoids, biogenetically assembled from two or three monomeric sesquiterpenoid units via diverse pathways, represent a unique class of natural products. The synthetic studies inspired by their biogenesis have offered significant impetus for the efficient construction of these architecturally complex frameworks. Here we provide an overview for the biomimetic […]
Necrosulfonamide inhibits necroptosis by selectively targeting the mixed lineage kinase domain-like protein
Daohong Liao, Liming Sun, Weilong Liu, Sudan He, Xiaodong Wang and Xiaoguang Lei*
Med. Chem. Commun., 2014,5, 333-337
Abstract: Through high-throughput screening of 200000 compounds and subsequent structure–activity relationship (SAR) studies we identified necrosulfonamide (NSA) as a potent small molecule inhibitor for necroptosis, induced by a combination of TNF-a, Smac mimetic, and z-VAD-fmk (T/S/Z). Applying a forward chemical genetic approach, we utilized an NSA based chemical probe to further reveal that NSA selectively […]
ortho-Quinone Methide Finds Its Application in Bioorthogonal Ligation
Qiang Li, Ting Dong, Xiaohui Liu, Xiaoyun Zhang, Xiaoying Yang, and Xiaoguang Lei*
Curr. Org. Chem. 2014, 18, 86-92
ABSTRACT: Bioorthogonal ligations have found widespread use in biomedical research for site selective labeling of biomolecules in living systems. Discovering new reactions to expand the toolbox of bioorthogonal chemistry remains an important, yet challenging, task as most reactions do not meet the stringent requirements of bioorthogonal reaction. As highly useful synthetic intermediates, ortho-quinone methides (oQMs) […]
Challenges and Strategies to the Total Syntheses of Fawcettimine-Type and Serratinine-Type Lycopodium Alkaloids
Wang, X.; Li, H.; Lei, X.*
Synlett. 2013 , DOI: 10.1055/s-0032-1316912 (Invited Synpacts Article).
The fawcettimine- and serratinine-type lycopodium alkaloids are a series of structurally complex but related natural products. These alkaloids have been the subjects of intense studies by the synthetic chemistry community, and many elegant strategies have been developed. Herein, we describe the recently disclosed synthetic strategies towards this unique family of natural products, in particular the […]
A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether
Li, Q.; Dong, T.; Liu, X.; Lei, X.*
J. Am. Chem. Soc. 2013 , 135 , 4996-4999 . ( News story describing this work was highlighted in Chem. & Eng. News 2013 , 14 , 37 ).
There is an increasing interest in the use of bioorthogonal ligation to advance biomedical research through selective labeling of biomolecules in living systems. Accordingly, discovering new reactions to expand the toolbox of bioorthogonal chemistry is of particular interest to chemical biologists. Herein we report a new bioorthogonal ligation enabled by click hetero-Diels–Alder (HDA) cycloaddition […]
Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B
Li, C.; Dong, T.; Dian, L.; Zhang, W.; Lei, X.*
Chem. Sci . 2013, 4, 1163-1167
Ainsliatrimers A and B are two recently isolated complex sesquiterpenoid natural products that display the unprecedented chemical motifs and remarkable anti-cancer activities. The exact structures as well as the mechanism of anti-cancer action for ainsliatrimers A and B remain to be elucidated. Here we report the first concise and biomimetic syntheses of (-)-ainsliatrimers A and […]
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 […]