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 […]
Shun Su, Dayle E. Acquilano, Jeevanandam Arumugasamy, Aaron B. Beeler, Erin L. Eastwood, Joshua R. Giguere, Ping Lan, Xiaoguang Lei, Geanna K. Min, Adam R. Yeager, Ya Zhou, James S. Panek, John K. Snyder, Scott E. Schaus, and John A. Porco, Jr.
Org. Lett . 2005 , 7 , 2751-2754
The synthesis of a complex hybrid oxime library is reported utilizing convergent ligation of alkoxyamine and carbonyl monomers via “chemical domain shuffling
Xiaoguang Lei, Nava Zaarur, Michael Y. Sherman, John A. Porco, Jr.
J. Org. Chem. 2005 , 70, 6474-6483
We have accomplished the synthesis of a complex chemical library via elaboration of angular epoxyquinol scaffolds with distinct skeletal frameworks. The key strategy involves highly stereocontrolled [4 + 2] Diels?Alder cycloadditions of chiral, nonracemic epoxyquinol dienes to generate the scaffolds. Further scaffold diversification involves hydrogenation, epimerization, dehydration, and condensation of the carbonyl group with alkoxyamine and carbazate building blocks. Further elaboration of the scaffolds also provided new skeletal frameworks using hydroxyl-directed Diels?Alder cycloaddition and reductive N?N bond cleavage. The overall process afforded 244 highly complex and functionalized compounds. Preliminary biological screening of the library uncovered six compounds which showed significant inhibition of Hsp 72 induction.
John A. Porco Jr., Prof. Dr. , Shun Su, Xiaoguang Lei, Sujata Bardhan, Scott D. Rychnovsky, Prof. Dr.
Angew. Chem. Int. Ed . 2006 , 45 , 5790-5792; Angew. Chem . 2006 , 118 , 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006 , 31 , 11 and Nature 2006 , 442 , 492-493)
Xiaoguang Lei and John A. Porco, Jr.
J. Am. Chem. Soc. 2006 , 128 , 14790-14791( News story describing this work was highlighted in Chem. & Eng. News 2006 , 45 , 9. )
The enantioselective total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C is reported. The approach involves tartrate-mediated, asymmetric nucleophilic epoxidation of a functionalized quinone monoketal to construct the highly substituted D-ring.
Peng, L. F.; Kim, S. S.; Matchacheep, S.; Lei, X .; Su, S.; Lin, W.; Runguphan, W.; Choe, W. H.; Sakamoto, N.; Beeler, A. B.; Porco, J. A., Jr.; Schreiber, S. L.; Chung, R. T.
Antimicrob. Agents Chemother . 2007 , 51 , 3756-3759
Using our high-throughput hepatitis C replicon assay to screen a library of over 8,000 novel diversity-oriented synthesis (DOS) compounds, we identified several novel compounds that regulate hepatitis C virus (HCV) replication, including two libraries of epoxides that inhibit HCV replication (best 50% effective concentration, < 0.5 μM). We then synthesized an analog of these compounds […]
Fay Ng, Heedong Yun, Xiaoguang Lei, Samuel J. Danishefsky, Jed Fahey, Katherine Stephenson, Charles Flexner, Lawrence Lee
Tetrahedron Lett. 2008 , 49 , 7178-7179
Panaxytriol is a nutraceutical-based active constituent of Korean red ginseng and is reported to exhibit potent anti-tumor properties. Its activity may be in part due to its induction of phase 2 chemoprotective enzymes. Its unique properties may have important implications in cancer therapeutics.
Xiaoguang Lei, Mingji Dai, Zihao Hua, Samuel J. Danishefsky
Tetrahedron Lett. 2008 , 49 , 6383-6385
The Letter describes a short and biomimetic synthesis of tricycloillicinone, which was found to enhance the action of choline acetyltransferase (ChAT). The synthetic route has two critical reactions: bulky, oxygenophilic methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR) promoted rearrangement of prenyl phenyl ether and photochemical cyclization. Furthermore, experiments were designed to explore the process of MABR-promoted rearrangement. It was found that the stereochemistry of deuterium labeled prenyl group was only partially scrambled, which suggests that there may be two possible reaction pathways involved in this process. It also suggests that the direct migration of prenyl group to para-position under these conditions is slightly favored over the Claisen-Cope process. The highly efficient synthetic route also provides important new opportunities to explore the biological behavior of tricycloillicinone. ? 2008 Elsevier Ltd. All rights reserved.
Xiaoguang Lei, Samuel J. Danishefsky
Adv. Synth. Catal. 2008 , 350, 1677-1681
The highly efficient synthesis of a novel heat shock protein 90 (Hsp90)-based anticancer agent, triazole-cycloproparadicicol, is described. The key step involves a fragment coupling using ‘click chemistry’ The preliminary biological evaluation of triazole-cycloproparadicicol is also reported.
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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 […]
Synthesis of a Polymer-Supported Anthracene and Its Application as a Dienophile Scavenger
Xiaoguang Lei and John A. Porco, Jr.
Org. Lett . 2004 , 6 , 795-798
A polymer-supported anthracene has been prepared and employed as a dienophile scavenger in Diels?Alder cycloadditions.
Convergent Synthesis of a Complex Oxime Library Using Chemical Domain Shuffling
Shun Su, Dayle E. Acquilano, Jeevanandam Arumugasamy, Aaron B. Beeler, Erin L. Eastwood, Joshua R. Giguere, Ping Lan, Xiaoguang Lei, Geanna K. Min, Adam R. Yeager, Ya Zhou, James S. Panek, John K. Snyder, Scott E. Schaus, and John A. Porco, Jr.
Org. Lett . 2005 , 7 , 2751-2754
The synthesis of a complex hybrid oxime library is reported utilizing convergent ligation of alkoxyamine and carbonyl monomers via “chemical domain shuffling
Stereocontrolled Synthesis of a Complex Library via Elaboration of Angular Epoxyquinol Scaffolds
Xiaoguang Lei, Nava Zaarur, Michael Y. Sherman, John A. Porco, Jr.
J. Org. Chem. 2005 , 70, 6474-6483
We have accomplished the synthesis of a complex chemical library via elaboration of angular epoxyquinol scaffolds with distinct skeletal frameworks. The key strategy involves highly stereocontrolled [4 + 2] Diels?Alder cycloadditions of chiral, nonracemic epoxyquinol dienes to generate the scaffolds. Further scaffold diversification involves hydrogenation, epimerization, dehydration, and condensation of the carbonyl group with alkoxyamine and carbazate building blocks. Further elaboration of the scaffolds also provided new skeletal frameworks using hydroxyl-directed Diels?Alder cycloaddition and reductive N?N bond cleavage. The overall process afforded 244 highly complex and functionalized compounds. Preliminary biological screening of the library uncovered six compounds which showed significant inhibition of Hsp 72 induction.
Total Synthesis and Structure Assignment of (+)-Hexacyclinol
John A. Porco Jr., Prof. Dr. , Shun Su, Xiaoguang Lei, Sujata Bardhan, Scott D. Rychnovsky, Prof. Dr.
Angew. Chem. Int. Ed . 2006 , 45 , 5790-5792; Angew. Chem . 2006 , 118 , 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006 , 31 , 11 and Nature 2006 , 442 , 492-493)
View Full Article
Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C1
Xiaoguang Lei and John A. Porco, Jr.
J. Am. Chem. Soc. 2006 , 128 , 14790-14791( News story describing this work was highlighted in Chem. & Eng. News 2006 , 45 , 9. )
The enantioselective total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C is reported. The approach involves tartrate-mediated, asymmetric nucleophilic epoxidation of a functionalized quinone monoketal to construct the highly substituted D-ring.
Identification of Novel Epoxide Inhibitors of HCV Replication Using High-Throughput Screening
Peng, L. F.; Kim, S. S.; Matchacheep, S.; Lei, X .; Su, S.; Lin, W.; Runguphan, W.; Choe, W. H.; Sakamoto, N.; Beeler, A. B.; Porco, J. A., Jr.; Schreiber, S. L.; Chung, R. T.
Antimicrob. Agents Chemother . 2007 , 51 , 3756-3759
Using our high-throughput hepatitis C replicon assay to screen a library of over 8,000 novel diversity-oriented synthesis (DOS) compounds, we identified several novel compounds that regulate hepatitis C virus (HCV) replication, including two libraries of epoxides that inhibit HCV replication (best 50% effective concentration, < 0.5 μM). We then synthesized an analog of these compounds […]
(3 R ,9 R ,10 R )-Panaxytriol: a molecular-based nutraceutical with possible application to cancer prevention and treatment
Fay Ng, Heedong Yun, Xiaoguang Lei, Samuel J. Danishefsky, Jed Fahey, Katherine Stephenson, Charles Flexner, Lawrence Lee
Tetrahedron Lett. 2008 , 49 , 7178-7179
Panaxytriol is a nutraceutical-based active constituent of Korean red ginseng and is reported to exhibit potent anti-tumor properties. Its activity may be in part due to its induction of phase 2 chemoprotective enzymes. Its unique properties may have important implications in cancer therapeutics.
Biomimetic total synthesis of tricycloillicinone and mechanistic studies toward the rearrangement of prenyl phenyl ethers
Xiaoguang Lei, Mingji Dai, Zihao Hua, Samuel J. Danishefsky
Tetrahedron Lett. 2008 , 49 , 6383-6385
The Letter describes a short and biomimetic synthesis of tricycloillicinone, which was found to enhance the action of choline acetyltransferase (ChAT). The synthetic route has two critical reactions: bulky, oxygenophilic methylaluminum bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR) promoted rearrangement of prenyl phenyl ether and photochemical cyclization. Furthermore, experiments were designed to explore the process of MABR-promoted rearrangement. It was found that the stereochemistry of deuterium labeled prenyl group was only partially scrambled, which suggests that there may be two possible reaction pathways involved in this process. It also suggests that the direct migration of prenyl group to para-position under these conditions is slightly favored over the Claisen-Cope process. The highly efficient synthetic route also provides important new opportunities to explore the biological behavior of tricycloillicinone. ? 2008 Elsevier Ltd. All rights reserved.
Efficient Synthesis of a Novel Resorcyclide as Anticancer Agent Based on Hsp90 inhibition
Xiaoguang Lei, Samuel J. Danishefsky
Adv. Synth. Catal. 2008 , 350, 1677-1681
The highly efficient synthesis of a novel heat shock protein 90 (Hsp90)-based anticancer agent, triazole-cycloproparadicicol, is described. The key step involves a fragment coupling using ‘click chemistry’ The preliminary biological evaluation of triazole-cycloproparadicicol is also reported.