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 […]
Benke Hong, Chao Li, Zhen Wang, Jie Chen, Houhua Li and Xiaoguang Lei?
J. Am. Chem. Soc. 2015, 137, 11946-11949
Abstract: We report herein the first total synthesis of (-)-incarviatone A (1) in 14 steps starting from commercially available inexpensive phenylacetic acid (9). Our early-stage synthesis relies on the scalable and sequential C-H functionalization to rapidly assemble the indanyl dialdehyde framework. Further biomimetic cascade strategy allows us to obtain the natural product in a one-pot […]
Chao Li, Alexander Jones, and Xiaoguang Lei
Nat. Prod. Rep. , 2015, DOI: 10.1039/C5NP00089K
Abstract: In this highlight we describe two case studies from our laboratory, involving the biomimetic syntheses and the biological mechanism elucidation of the bioactive oligomeric sesquiterpenoids, (+)-ainsliadimer A (4) and (?)-ainsliatrimer A (5). Ainsliadimer A possesses potent anti-inflammatory activity by inhibition of the NF-κB signalling pathway?via?binding at a previously untargeted allosteric site. (?)-Ainsliatrimer A induces […]
Qin, X.; Chen, B.; Fu, J.; Shan, L.; Lei, X.; Zhang, W
Eur. J. Med. Chem. 2015, 102, 256-265.
The eight novel ivangustin enantiomer analogues possessing α-methylene-γ-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 μM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 μM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities.
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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 […]
Enantioselective Total Synthesis of (-)-Incarviatone A
Benke Hong, Chao Li, Zhen Wang, Jie Chen, Houhua Li and Xiaoguang Lei?
J. Am. Chem. Soc. 2015, 137, 11946-11949
Abstract: We report herein the first total synthesis of (-)-incarviatone A (1) in 14 steps starting from commercially available inexpensive phenylacetic acid (9). Our early-stage synthesis relies on the scalable and sequential C-H functionalization to rapidly assemble the indanyl dialdehyde framework. Further biomimetic cascade strategy allows us to obtain the natural product in a one-pot […]
Synthesis and mode of action of oligomeric sesquiterpene lactones
Chao Li, Alexander Jones, and Xiaoguang Lei
Nat. Prod. Rep. , 2015, DOI: 10.1039/C5NP00089K
Abstract: In this highlight we describe two case studies from our laboratory, involving the biomimetic syntheses and the biological mechanism elucidation of the bioactive oligomeric sesquiterpenoids, (+)-ainsliadimer A (4) and (?)-ainsliatrimer A (5). Ainsliadimer A possesses potent anti-inflammatory activity by inhibition of the NF-κB signalling pathway?via?binding at a previously untargeted allosteric site. (?)-Ainsliatrimer A induces […]
Synthesis, cytotoxicity and inhibition of NO production of ivangustin enantiomer analogues
Qin, X.; Chen, B.; Fu, J.; Shan, L.; Lei, X.; Zhang, W
Eur. J. Med. Chem. 2015, 102, 256-265.
The eight novel ivangustin enantiomer analogues possessing α-methylene-γ-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 μM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 μM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities.
Recent Advances in the Total Synthesis of Prenylflavonoid and Related Diels—Alder Natural Products
Han, J.; Jones, A.; Lei, X
Synthesis 2015, 47, 1519-1533.