Robert Anthony Mook Jr. | Scholars@Duke

Robert Anthony Mook Jr.
Assistant Professor in Medicine

Current Appointments & Affiliations

Assistant Professor in Medicine, Medicine, Gastroenterology, Medicine 2011

Contact Information

905 Lasalle Street , Mailbox 3256, Genetic Science Research Bldg 1, Rm1063, Durham, NC 27710
Genetic Science Research Bldg. 1 Duke Box 3256, 595 Lasalle Street, Room 1063, Durham, NC 27710
robert.mook@duke.edu (919) 889-2273

Background
Education, Training, & Certifications
- Ph.D., Columbia University, College of Physicians and Surgeons 1985
Duke Appointment History
- Instructor Temporary in the Department of Medicine, Medicine, Gastroenterology, Medicine 2010 - 2011
Research
Selected Grants
- Inhibitors of TrkB Signaling awarded by National Institutes of Health 2019 - 2024
- Inhibition of Wnt/B-Catenin Signaling in Colorectal Cancer Therapy awarded by National Institutes of Health 2013 - 2019
- Inhibitors of TrkB Signaling awarded by National Institutes of Health 2016 - 2019
- Targeting the WNT/beta-catenin pathway in triple negative breast cancer awarded by Department of Defense 2013 - 2017
- Bone-targeted calcium channel agonists for osteoporosis awarded by UH Harrington Discovery Institute 2015 - 2017
- Clinical Oncology Research Career Development Program awarded by National Institutes of Health 2009 - 2015
External Relationships
- LVM Bioscience
- LVM Biosciences
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Wang, Jiangbo, Xiu-Rong Ren, Hailan Piao, Shengli Zhao, Takuya Osada, Richard T. Premont, Robert A. Mook, Michael A. Morse, Herbert Kim Lyerly, and Wei Chen. “Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.” Biochem J 476, no. 3 (February 8, 2019): 535–46. https://doi.org/10.1042/BCJ20180385.
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  - Mook, Robert A., Jiangbo Wang, Xiu-Rong Ren, Hailan Piao, H Kim Lyerly, and Wei Chen. “Identification of novel triazole inhibitors of Wnt/β-catenin signaling based on the Niclosamide chemotype.” Bioorg Med Chem Lett 29, no. 2 (January 15, 2019): 317–21. https://doi.org/10.1016/j.bmcl.2018.11.022.
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  - Wang, Jiangbo, Robert A. Mook, Xiu-Rong Ren, Qingfu Zhang, Genevieve Jing, Min Lu, Ivan Spasojevic, H Kim Lyerly, David Hsu, and Wei Chen. “Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.” Bioorg Med Chem 26, no. 20 (November 1, 2018): 5435–42. https://doi.org/10.1016/j.bmc.2018.09.016.
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  - Chen, Wei, Robert A. Mook, Richard T. Premont, and Jiangbo Wang. “Niclosamide: Beyond an antihelminthic drug.” Cell Signal 41 (January 2018): 89–96. https://doi.org/10.1016/j.cellsig.2017.04.001.
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  - Bhattacharyya, Jayanta, Xiu-Rong Ren, Robert A. Mook, Jiangbo Wang, Ivan Spasojevic, Richard T. Premont, Xinghai Li, Ashutosh Chilkoti, and Wei Chen. “Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth.” Nanoscale 9, no. 34 (August 31, 2017): 12709–17. https://doi.org/10.1039/c7nr01973d.
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  - Mook, Robert A., Xiu-Rong Ren, Jiangbo Wang, Hailan Piao, Larry S. Barak, H. Kim Lyerly, and Wei Chen. “Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis.” Bioorg Med Chem 25, no. 6 (March 15, 2017): 1804–16. https://doi.org/10.1016/j.bmc.2017.01.046.
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  - Geer Wallace, M Ariel, Do-Yeon Kwon, Douglas H. Weitzel, Chen-Ting Lee, Tesia N. Stephenson, Jen-Tsan Chi, Robert A. Mook, Mark W. Dewhirst, Jiyong Hong, and Michael C. Fitzgerald. “Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.” J Proteome Res 15, no. 8 (August 5, 2016): 2688–96. https://doi.org/10.1021/acs.jproteome.6b00237.
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  - Kanju, Patrick, Yong Chen, Whasil Lee, Michele Yeo, Suk Hee Lee, Joelle Romac, Rafiq Shahid, et al. “Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain.” Sci Rep 6 (June 1, 2016): 26894. https://doi.org/10.1038/srep26894.
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  - Ren, X. R., J. Wang, T. Osada, R. A. Mook, M. A. Morse, L. S. Barak, H. K. Lyerly, and W. Chen. “Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth.” Breast Cancer Res 17, no. 1 (December 2015): 528. https://doi.org/10.1186/s13058-015-0528-9.
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  - Kwon, Do-Yeon, Hye Eun Lee, Douglas H. Weitzel, Kyunghye Park, Sun Hee Lee, Chen-Ting Lee, Tesia N. Stephenson, et al. “Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition.” J Med Chem 58, no. 19 (October 8, 2015): 7659–71. https://doi.org/10.1021/acs.jmedchem.5b01220.
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  - Mook, Robert A., Jiangbo Wang, Xiu-Rong Ren, Minyong Chen, Ivan Spasojevic, Larry S. Barak, H Kim Lyerly, and Wei Chen. “Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure.” Bioorg Med Chem 23, no. 17 (September 1, 2015): 5829–38. https://doi.org/10.1016/j.bmc.2015.07.001.
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  - Mook, Robert A., Minyong Chen, Jiuyi Lu, Larry S. Barak, H Kim Lyerly, and Wei Chen. “Small molecule modulators of Wnt/β-catenin signaling.” Bioorg Med Chem Lett 23, no. 7 (April 1, 2013): 2187–91. https://doi.org/10.1016/j.bmcl.2013.01.101.
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  - Rheault, T. R., J. C. Stellwagen, G. M. Adjabeng, K. R. Hornberger, K. G. Petrov, A. G. Waterson, S. H. Dickerson, et al. “Discovery of dabrafenib: A selective inhibitor of Raf Kinases with antitumor activity against B-Raf-driven tumors.” Acs Medicinal Chemistry Letters 4, no. 3 (March 14, 2013): 358–62. https://doi.org/10.1021/ml4000063.
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  - Wang, Jiangbo, Robert A. Mook, Jiuyi Lu, David M. Gooden, Anthony Ribeiro, Anchen Guo, Larry S. Barak, H Kim Lyerly, and Wei Chen. “Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling.” Bioorganic & Medicinal Chemistry 20, no. 22 (November 2012): 6751–57. https://doi.org/10.1016/j.bmc.2012.09.030.
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  - Wang, Jiangbo, Jiuyi Lu, Robert A. Mook, Min Zhang, Shengli Zhao, Larry S. Barak, Jonathan H. Freedman, H Kim Lyerly, and Wei Chen. “The insecticide synergist piperonyl butoxide inhibits hedgehog signaling: assessing chemical risks.” Toxicol Sci 128, no. 2 (August 2012): 517–23. https://doi.org/10.1093/toxsci/kfs165.
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  - Stellwagen, John C., George M. Adjabeng, Marc R. Arnone, Scott H. Dickerson, Chao Han, Keith R. Hornberger, Alastair J. King, et al. “Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup.” Bioorg Med Chem Lett 21, no. 15 (August 1, 2011): 4436–40. https://doi.org/10.1016/j.bmcl.2011.06.021.
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  - Wang, Jiangbo, Larry S. Barak, Robert A. Mook, and Wei Chen. “Glucocorticoid hedgehog agonists in neurogenesis.” Vitam Horm 87 (2011): 207–15. https://doi.org/10.1016/B978-0-12-386015-6.00030-5.
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  - Wood, Edgar R., Lisa Shewchuk, Anne Hassel, Jim Nichols, Anne T. Truesdale, Danielle Smith, H Luke Carter, et al. “Discovery of an inhibitor of insulin-like growth factor 1 receptor activation: implications for cellular potency and selectivity over insulin receptor.” Biochem Pharmacol 78, no. 12 (December 15, 2009): 1438–47. https://doi.org/10.1016/j.bcp.2009.07.022.
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  - Emmitte, K. A., G. M. Adjabeng, C. Webb Andrews, J. G. Badiang Alberti, R. Bambal, S. D. Chamberlain, R. G. Davis-Ward, et al. “Corrigendum to "Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding" [Bioorg. Med. Chem. Lett. 19 (2009) 1694] (DOI:10.1016/j.bmcl.2009.01.094).” Bioorganic and Medicinal Chemistry Letters 19, no. 9 (May 1, 2009): 2604. https://doi.org/10.1016/j.bmcl.2009.01.114.
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  - Emmitte, Kyle A., George M. Adjabeng, C Webb Andrews, Jennifer G Badiang Alberti, Ramesh Bambal, Stanley D. Chamberlain, Ronda G. Davis-Ward, et al. “Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.” Bioorg Med Chem Lett 19, no. 6 (March 15, 2009): 1694–97. https://doi.org/10.1016/j.bmcl.2009.01.094.
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  - Emmitte, Kyle A., Brian J. Wilson, Erich W. Baum, Holly K. Emerson, Kevin W. Kuntz, Kristen E. Nailor, James M. Salovich, et al. “Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R).” Bioorg Med Chem Lett 19, no. 3 (February 1, 2009): 1004–8. https://doi.org/10.1016/j.bmcl.2008.11.058.
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  - Emmitte, Kyle A., C Webb Andrews, Jennifer G. Badiang, Ronda G. Davis-Ward, Hamilton D. Dickson, David H. Drewry, Holly K. Emerson, et al. “Discovery of thiophene inhibitors of polo-like kinase.” Bioorg Med Chem Lett 19, no. 3 (February 1, 2009): 1018–21. https://doi.org/10.1016/j.bmcl.2008.11.041.
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  - Chamberlain, Stanley D., Anikó M. Redman, Joseph W. Wilson, Felix Deanda, J Brad Shotwell, Roseanne Gerding, Huangshu Lei, et al. “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.” Bioorg Med Chem Lett 19, no. 2 (January 15, 2009): 360–64. https://doi.org/10.1016/j.bmcl.2008.11.077.
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  - Chamberlain, Stanley D., Joseph W. Wilson, Felix Deanda, Samarjit Patnaik, Anikó M. Redman, Bin Yang, Lisa Shewchuk, et al. “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.” Bioorg Med Chem Lett 19, no. 2 (January 15, 2009): 469–73. https://doi.org/10.1016/j.bmcl.2008.11.046.
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  - Cheung, M., K. W. Kuntz, M. Pobanz, J. M. Salovich, B. J. Wilson, C. W. Andrews, L. M. Shewchuk, et al. “Imidazo[5,1-f][1,2,4]triazin-2-amines as novel inhibitors of polo-like kinase 1.” Bioorg Med Chem Lett 18, no. 23 (December 1, 2008): 6214–17. https://doi.org/10.1016/j.bmcl.2008.09.100.
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  - Harris, Philip A., Amogh Boloor, Mui Cheung, Rakesh Kumar, Renae M. Crosby, Ronda G. Davis-Ward, Andrea H. Epperly, et al. “Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor.” J Med Chem 51, no. 15 (August 14, 2008): 4632–40. https://doi.org/10.1021/jm800566m.
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  - Lansing, Timothy J., Randy T. McConnell, Derek R. Duckett, Glenn M. Spehar, Victoria B. Knick, Daniel F. Hassler, Nobuhiro Noro, et al. “In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.” Mol Cancer Ther 6, no. 2 (February 2007): 450–59. https://doi.org/10.1158/1535-7163.MCT-06-0543.
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  - Petrov, Kimberly G., Yue-Mei Zhang, Malcolm Carter, G Stuart Cockerill, Scott Dickerson, Cassandra A. Gauthier, Yu Guo, et al. “Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.” Bioorg Med Chem Lett 16, no. 17 (September 1, 2006): 4686–91. https://doi.org/10.1016/j.bmcl.2006.05.090.
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  - Heerdt, Paul M., Richard Kang, Andrew The’, Mir Hashim, Robert J. Mook, and John J. Savarese. “Cardiopulmonary effects of the novel neuromuscular blocking drug GW280430A (AV430A) in dogs.” Anesthesiology 100, no. 4 (April 2004): 846–51. https://doi.org/10.1097/00000542-200404000-00014.
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  - Savarese, John J., Matthew R. Belmont, Mir A. Hashim, Robert A. Mook, Eric E. Boros, Vicente Samano, Sanjay S. Patel, et al. “Preclinical pharmacology of GW280430A (AV430A) in the rhesus monkey and in the cat: a comparison with mivacurium.” Anesthesiology 100, no. 4 (April 2004): 835–45. https://doi.org/10.1097/00000542-200404000-00013.
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  - Boros, Eric E., Vicente Samano, John A. Ray, James B. Thompson, David K. Jung, Istvan Kaldor, Cecilia S. Koble, et al. “Neuromuscular blocking activity and therapeutic potential of mixed-tetrahydroisoquinolinium halofumarates and halosuccinates in rhesus monkeys.” J Med Chem 46, no. 12 (June 5, 2003): 2502–15. https://doi.org/10.1021/jm020574+.
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  - Kaldor, I., P. L. Feldman, R. A. Mook, J. A. Ray, V. Samano, A. M. Sefler, J. B. Thompson, B. R. Travis, and E. E. Boros. “Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration.” J Org Chem 66, no. 10 (May 18, 2001): 3495–3501. https://doi.org/10.1021/jo010032k.
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  - Samano, V., J. A. Ray, J. B. Thompson, R. A. Mook, D. K. Jung, C. S. Koble, M. T. Martin, et al. “Synthesis of ultra-short-acting neuromuscular blocker GW 0430: a remarkably stereo- and regioselective synthesis of mixed tetrahydroisoquinolinium chlorofumarates.” Org Lett 1, no. 12 (December 16, 1999): 1993–96. https://doi.org/10.1021/ol9911573.
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  - Henke, B. R., K. K. Adkison, S. G. Blanchard, L. M. Leesnitzer, R. A. Mook, K. D. Plunket, J. A. Ray, C. Roberson, R. Unwalla, and T. M. Willson. “Synthesis and biological activity of a novel series of indole-derived PPARgamma agonists.” Bioorg Med Chem Lett 9, no. 23 (December 6, 1999): 3329–34. https://doi.org/10.1016/s0960-894x(99)00603-4.
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  - Brown, K. K., B. R. Henke, S. G. Blanchard, J. E. Cobb, R. Mook, I. Kaldor, S. A. Kliewer, et al. “A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat.” Diabetes 48, no. 7 (July 1999): 1415–24. https://doi.org/10.2337/diabetes.48.7.1415.
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  - Boros, E. E., E. C. Bigham, G. E. Boswell, J. Mook, S. S. Patel, J. J. Savarese, J. A. Ray, et al. “Erratum: Bis- and mixed-tetrahydroisoquinolinium chlorofumarates: New ultra-short-acting nondepolarizing neuromuscular blockers (Journal of Medicinal Chemistry (1999) 42 (207)).” Journal of Medicinal Chemistry 42, no. 6 (March 25, 1999): 1114. https://doi.org/10.1021/jm990060j.
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  - Boros, E. E., E. C. Bigham, G. E. Boswell, R. A. Mook, S. S. Patel, J. J. Savarese, J. A. Ray, et al. “Bis- and mixed-tetrahydroisoquinolinium chlorofumarates: new ultra-short-acting nondepolarizing neuromuscular blockers.” J Med Chem 42, no. 2 (January 28, 1999): 206–9. https://doi.org/10.1021/jm980597h.
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  - Henke, B. R., S. G. Blanchard, M. F. Brackeen, K. K. Brown, J. E. Cobb, J. L. Collins, W. W. Harrington, et al. “N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.” J Med Chem 41, no. 25 (December 3, 1998): 5020–36. https://doi.org/10.1021/jm9804127.
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  - Lewis, J. G., K. Y. Lin, A. Kothavale, W. M. Flanagan, M. D. Matteucci, R. B. DePrince, R. A. Mook, R. W. Hendren, and R. W. Wagner. “A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA.” Proc Natl Acad Sci U S A 93, no. 8 (April 16, 1996): 3176–81. https://doi.org/10.1073/pnas.93.8.3176.
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  - Tian, G., R. A. Mook, M. L. Moss, and S. V. Frye. “Mechanism of time-dependent inhibition of 5 alpha-reductases by delta 1-4-azasteroids: toward perfection of rates of time-dependent inhibition by using ligand-binding energies.” Biochemistry 34, no. 41 (October 17, 1995): 13453–59. https://doi.org/10.1021/bi00041a024.
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  - Mook, R. A., K. Lackey, and C. Bennett. “Synthesis of phenanthridin-3-one derivatives: Non-steroidal inhibitors of steroid 5-α-reductase.” Tetrahedron Letters 36, no. 23 (June 5, 1995): 3969–72. https://doi.org/10.1016/0040-4039(95)00690-E.
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  - Frye, S. V., C. D. Haffner, P. R. Maloney, R. A. Mook, G. F. Dorsey, R. N. Hiner, C. M. Cribbs, T. N. Wheeler, J. A. Ray, and R. C. Andrews. “6-Azasteroids: structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase.” J Med Chem 37, no. 15 (July 22, 1994): 2352–60. https://doi.org/10.1021/jm00041a014.
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  - Frye, S. V., C. D. Haffner, P. R. Maloney, R. A. Mook, G. F. Dorsey, R. N. Hiner, K. W. Batchelor, H. N. Bramson, J. D. Stuart, and S. L. Schweiker. “6-Azasteroids: potent dual inhibitors of human type 1 and 2 steroid 5 alpha-reductase.” J Med Chem 36, no. 26 (December 24, 1993): 4313–15. https://doi.org/10.1021/jm00078a022.
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  - Mook, R. A. “Purification of trifluoroacetic anhydride [1].” Chemical and Engineering News 65, no. 13 (December 1, 1987).
  - Stork, G., and R. Mook. “Vinyl Radical Cyclizations Mediated by the Addition of Stannyl Radicals to Triple Bonds.” Journal of the American Chemical Society 109, no. 9 (April 1, 1987): 2829–31. https://doi.org/10.1021/ja00243a049.
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  - Stork, G., and R. Mook. “Five vs six membered ring formation in the vinyl radical cyclization.” Tetrahedron Letters 27, no. 38 (January 1, 1986): 4529–32. https://doi.org/10.1016/S0040-4039(00)84995-3.
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  - Stork, G., R. Mook, S. A. Biller, and S. D. Rychnovsky. “Free-Radical Cyclization of Bromoacetals. Use in the Construction of Bicyclic Acetals and Lactones.” Journal of the American Chemical Society 105, no. 11 (January 1, 1983): 3741–42. https://doi.org/10.1021/ja00349a082.
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  - Stork, G., and R. Mook. “Vinyl Radical Cyclization. 2. Dicyclization via Selective Formation of Unsaturated Vinyl Radicals by Intramolecular Addition to Triple Bonds. Applications to the Synthesis of Butenolides and Furans.” Journal of the American Chemical Society 105, no. 11 (January 1, 1983): 3720–22. https://doi.org/10.1021/ja00349a067.
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Education, Training, & Certifications

Duke Appointment History

Selected Grants

External Relationships

Selected Publications

Academic Articles