Utilizing a late-stage enamine bromofunctionlization strategy, we have accomplished a 12-step total synthesis of (-)-huperzine Q as well as the first total syntheses of (+)-lycopladines B and C. We also report an unprecedented X-ray crystal structure of an unusual epoxyamine intermediate and demonstrate its useful synthetic application in natural product synthesis.
Tie-Mei Li, Jie Chen, Xiangke Li, Xiao-Jun Ding, Yao Wu , Li-Feng Zhao, She Chen, Xiaoguang Lei *,Meng-Qiu Dong *
Anal. Chem. , 2013 , 85 ,9281
Under favorable conditions, Caenorhabditis elegans larvae grow into reproductive adults after a series of molting cycles. When environmental conditions are harsh, they arrest as dauer larvae. Dafachronic acid (DA), a C. elegans steroid hormone, is required for reproductive development. Here, we report a mass spectrometry (MS) method for absolute quantitation of DA in C. elegans. […]
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 […]
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 […]
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 […]
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. […]
Herein, we report an efficient approach for exploring the novel anti-cancer mechanism of (-)-ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ-ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by […]
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 […]
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 Syntheses of (-)-Huperzine Q, (+)-Lycopladines B and C
Benke Hong, Houhua Li, Jinbao Wu, Jing Zhang, and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2015, 54, 1011-1015
Utilizing a late-stage enamine bromofunctionlization strategy, we have accomplished a 12-step total synthesis of (-)-huperzine Q as well as the first total syntheses of (+)-lycopladines B and C. We also report an unprecedented X-ray crystal structure of an unusual epoxyamine intermediate and demonstrate its useful synthetic application in natural product synthesis.
Absolute Quantification of a Steroid Hormone that Regulates Development in Caenorhabditis elegans
Tie-Mei Li, Jie Chen, Xiangke Li, Xiao-Jun Ding, Yao Wu , Li-Feng Zhao, She Chen, Xiaoguang Lei *,Meng-Qiu Dong *
Anal. Chem. , 2013 , 85 ,9281
Under favorable conditions, Caenorhabditis elegans larvae grow into reproductive adults after a series of molting cycles. When environmental conditions are harsh, they arrest as dauer larvae. Dafachronic acid (DA), a C. elegans steroid hormone, is required for reproductive development. Here, we report a mass spectrometry (MS) method for absolute quantitation of DA in C. elegans. […]
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 […]
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 […]
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 […]
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. […]
Probing the Anti-cancer Mechanism of (-)-Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation
Chao Li, Ting Dong, Qiang Li, and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2014, 53, 12111-12115
Herein, we report an efficient approach for exploring the novel anti-cancer mechanism of (-)-ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ-ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by […]
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 […]
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 […]