Richard I. Duclos, Jr., Ph.D.
Richard I. Duclos, Jr., Ph.D. Northeastern University Department of Pharmaceutical Sciences 140 The Fenway Building, Room 123 360 Huntington Avenue Boston, MA 02115 (617) 373-3163 [email protected] CAREER SUMMARY Accomplished organic chemist with expertise in early stage medicinal chemistry and protein assay development. Prolific record of developing and implementing solutions to challenging chemical, medicinal, biophysical, and biochemical research problems. Respected technical expert in spectroscopy providing leadership in lipid biochemistry and drug discovery. EXPERTISE Organic Synthesis • Spectroscopy • Radiosynthesis • Protein Chemistry Experimental Design • Route Selection/Strategy • Project Coordination/Leadership Enzyme Inhibition Assay Development • Technical Writing WORK EXPERIENCE 2010-Present: Research Assistant Professor in the Dept. of Pharmaceutical Sciences Northeastern University, Boston, MA • Radiosynthesis and pharmacology of endocannabinoids 2005-2010: Research Assistant Professor in the Center for Drug Discovery Northeastern University, Boston, MA • Designed and synthesized inhibitors for human diacylglycerol lipase (hDAGL-) • Developed high-throughputable assay for DAGL and related lipases 2004-2005: Principal Research Scientist in the Center for Drug Discovery Northeastern University, Boston, MA with Professor Alexandros Makriyannis • Laboratory supervision and editing of manuscripts • Performed the synthesis of endocannabinoid-related molecules 1989-2004: Research Assistant in the Department of Physiology and Biophysics Boston University School of Medicine, Boston, MA with Professor G. Graham Shipley • Synthesized sn-glycero-3-phosphocholines, D-erythro-sphingolipids, neutral glycosphingolipids, lipids with stable isotopic (13C) and radioisotopic (3H) labels • Performed chemo-enzymatic and chemical syntheses of gangliosides • Human LDL receptor protein over-expression in SF9 cells and affinity purification 1987-1989: Postdoctoral Fellow in the School of Pharmacy University of Connecticut, Storrs, CT with Professor Alexandros Makriyannis • Research resulted in the syntheses of new antineoplastic phospholipids 1986-1987: Research Chemist at Molecular Probes, Inc. (Invitrogen) Eugene, OR with Dr. Richard P. Haugland • Performed the synthesis and development of new fluorescently-labeled products 1984-1985: Postdoctoral Visiting Research Chemist in the School of Pharmacy University of California, San Francisco, CA with Professor Betty-ann Hoener • Research resulted in the syntheses of 14C-labeled nitrofuran antibacterials EDUCATION 1978-1984: University of California, Berkeley Ph.D. (1985) in Chemistry (Organic); Cumulative GPA 3.983 Research Supervisor: Professor Henry Rapoport 1974-1978: University of New Hampshire, Durham B.S. (1978) in Chemistry (with thesis); Cumulative GPA 3.669 Richard I. Duclos, Jr., Ph.D. (curriculum vitae, page 2 of 6) AWARDS AND SOCIETY AFFILIATIONS International Cannabinoid Research Society (2008-); Sigma Xi (1987-); Alpha Chi Sigma (1979-); Phi Beta Kappa (1978-); Phi Kappa Phi (1977-); University of New Hampshire Analytical Chemistry Award to a Junior (1977); American Chemical Society (1977-); University of New Hampshire Merit Scholarship (1974-1978) PUBLICATIONS R. I. Duclos, Jr., K. P. C. Vollhardt and L. S. Yee, "4-Benzocyclobutadiene-5cyclopentadienylcobalt, A New 'Aromatic' Sandwich Complex," J. Organometal. Chem. 1979, 174, 109-114. R. I. Duclos, Jr., J. S. Tung and H. Rapoport, "A High-Yield Modification of the Pschorr Phenanthrene Synthesis," J. Org. Chem. 1984, 49, 5243-5246. (cited by M. Fieser, "Fieser and Fieser's Reagents for Organic Synthesis," John Wiley & Sons: New York, 1986; Vol. 12, pp. 449-450.) R. I. Duclos, Jr., "Spiro-alkylation," Ph.D. Thesis, 1985, University of California, Berkeley. R. I. Duclos, Jr. and B.-a. Hoener, "Syntheses of 2-(Diacetoxymethyl-14C)-5-nitrofuran and Carbon-14 Labeled Nitrofurazone," J. Label. Compounds 1986, 23, 103-108. O. H. Abdelmageed, R. I. Duclos, Jr., R. G. Griffin, D. J. Siminovitch, M. J. Ruocco and A. Makriyannis, "Syntheses of 2H- and 13C-labeled 1,2-di-O-hexadecyl-sn-glycero3-phosphoethanolamines and 1,2-di-O-hexadecyl-sn-glycero-3-phosphocholines," Chem. Phys. Lipids 1989, 50, 163-169. O. H. Abdelmageed, R. I. Duclos, Jr., E. Abushanab and A. Makriyannis, "Chirospecific syntheses of 2H- and 13C-labeled 1-O-alkyl-2-O-alkyl'-sn-glycero-3phosphoethanolamines and 1-O-alkyl-2-O-alkyl'-sn-glycero-3-phosphocholines," Chem. Phys. Lipids 1990, 54, 49-59. D. L. Melchior, A. Carruthers, A. Makriyannis, R. I. Duclos, Jr. and O. H. Abdel-Mageed, "Alterations in red blood cell sugar transport by nanomolar concentrations of alkyl lysophospholipid," Biochim. Biophys. Acta 1990, 1028, 1-8. D. R. Kodali and R. I. Duclos, Jr., "Debenzylation and detritylation by bromodimethylborane: Synthesis of mono-acid or mixed-acid 1,2- or 2,3-diacylsn-glycerols," Chem. Phys. Lipids 1992, 61, 169-173. R. I. Duclos, Jr. and A. Makriyannis, "Syntheses of All Four Stereoisomers Which Are Conformationally Constrained 1,4-Dioxanyl Analogs of the Antineoplastic Ether Lipid ET-18-OCH3," J. Org. Chem. 1992, 57, 6156-6163. R. I. Duclos, Jr., "Synthesis of 1-palmitoyl-2-hexadecyl-sn-glycero-3-phosphocholine (PHPC)," Chem. Phys. Lipids 1993, 66, 161-170. J. Shah, R. I. Duclos, Jr. and G. G. Shipley, "Structure and Thermotropic Properties of 1-Stearoyl-2-acetyl-phosphatidylcholine Bilayer Membranes," Biophys. J. 1994, 66, 1469-1478. Richard I. Duclos, Jr., Ph.D. (curriculum vitae, page 3 of 6) PUBLICATIONS (continued) R. I. Duclos, Jr., H. H. Chia, O. H. Abdelmageed, H. Esber, D. J. Fournier and A. Makriyannis, "Syntheses of Racemic and Nearly Optically Pure Ether Lipids and Evaluation of in Vitro Antineoplastic Activities," J. Med. Chem. 1994, 37, 4147-4154. J. Moring, R. I. Duclos, Jr., J.-H. Zhang, L. G. Herbette, X. Xie and A. Makriyannis, "Single crystal X-ray structures of the two 4-heptadecyl derivatives of (1R,5S)-3,6,8trioxabicyclo[3.2.1]octane," Chem. Phys. Lipids 1995, 77, 99-112. J. Shah, J. M. Atienza, R. I. Duclos, Jr., A. V. Rawlings, Z. Dong and G. G. Shipley, "Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide: Effect of hydration," J. Lipid Res. 1995, 36, 1936-1944. S. Lin, R. I. Duclos, Jr. and A. Makriyannis, "Syntheses of 1,2-di-O-palmitoyl-snglycero-3-phosphocholine (DPPC) and analogs with 13C- and 2H-labeled choline head groups," Chem. Phys. Lipids 1997, 86, 171-181. K. Saxena, R. I. Duclos, P. Zimmermann, R. R. Schmidt and G. G. Shipley, "Structure and properties of totally synthetic galacto- and gluco-cerebrosides," J. Lipid Res. 1999, 40, 839-849. R. I. Duclos, Jr., "The total synthesis of ganglioside GM3," Carb. Res. 2000, 328, 489-507. K. Saxena, R. I. Duclos, Jr., P. K. Sripada and G. G. Shipley, "Unusual hydration properties of C16:0 sulfatide bilayer membranes," Biophys. J. 2000, 79, 385-393. R. I. Duclos, Jr., "The total syntheses of D-erythro-sphingosine, N-palmitoylsphingosine (ceramide), and glucosylceramide (cerebroside) via an azidosphingosine intermediate," Chem. Phys. Lipids 2001, 111, 111-138. S. Lin, R. I. Duclos, Jr. and A. Makriyannis, "Preparation of optically pure 4(hydroxymethyl)-2-pentadecyl-1,3-dioxolanes and their corresponding phosphodiester ether lipid derivatives," Chem. Phys. Lipids 2001, 113, 111-122. J. Ho, R. I. Duclos, Jr. and J. A. Hamilton, "Interactions of acylcarnitines with model membranes: A 13C NMR study," J. Lipid Res. 2002, 43, 1429-1439. G. A. Thakur, R. I. Duclos, Jr., A. Makriyannis, "Natural cannabinoids: Templates for drug discovery," Life Sci. 2005, 78, 454-466. G. A. Thakur, S. P. Nikas, R. I. Duclos, Jr., A. Makriyannis, "Methods for the synthesis of cannabinergic ligands," Methods Mol. Med. 2006, 123, 113-148. H. Zheng, R. I. Duclos, Jr., C. C. Smith, H. W. Farber, R. A. Zoeller, "Synthesis and biological properties of the fluorescent ether lipid precursor, 1-O-[9'-(1"-pyrenyl)]nonylsn-glycerol," J. Lipid Res. 2006, 47, 633-642. D. Lu, K. V. Vemuri, R. I. Duclos, Jr., A. Makriyannis, "The cannabinergic system as a target for anti-inflammatory therapies," Curr. Top. Med. Chem. 2006, 6, 1401-1426. Richard I. Duclos, Jr., Ph.D. (curriculum vitae, page 4 of 6) PUBLICATIONS (continued) S. K. Vadivel, S. Vardarajan, R. I. Duclos, Jr., J. T. Wood, A. Makriyannis, "Conformationally constrained analogues of 2-arachidonoylglycerol," Bioorg. Med. Chem. Lett. 2007, 17, 5959-5963. A. D. Khanolkar, D. Lu, M. Ibrahim, R. I. Duclos, Jr., G. A. Thakur, T. P. Malan, Jr., F. Porreca, V. Veerappan, X. Tian, C. George, D. A. Parrish, D. P. Papahatjis, A. Makriyannis, "Cannabilactones: A novel class of CB2 selective agonists with peripheral analgesic activity," J. Med. Chem. 2007, 50, 6493-6500. R. I. Duclos, Jr., D. Lu, J. Guo, A. Makriyannis, "Synthesis and characterization of 2Substituted bornane pharmacophores for novel cannabinergic ligands," Tetrahedron Lett. 2008, 49, 5587-5589. D. Lu, J. Guo, R. I. Duclos, Jr., A. L. Bowman, A. Makriyannis, "Bornyl- and isobornyl8-tetrahydrocannabinols: A novel class of cannabinergic ligands," J. Med. Chem. 2008, 51, 6393-6399. R. I. Duclos, Jr., S. J. Gatley, S. R. Bhatt, M. Johnston, "The preparation of 2-O-[1'14 C]arachidonoyl-1-O-stearoyl-sn-glycerol," J. Labelled Comp. Radiopharm. 2009, 52, 324-326. R. Sharma, S. K. Vadivel, R. I. Duclos, Jr., A. Makriyannis, "Open vessel mode microwave-assisted synthesis of 2-oxazolines from carboxylic acids," Tetrahedron Lett. 2009, 50, 5780-5782. R. I. Duclos, Jr., "The total synthesis of 2-O-arachidonoyl-1-O-stearoyl-snglycero-3-phosphocholine-1,3,1'-13C3 and -2,1'-13C2 by a novel multienzyme method," Chem. Phys. Lipids 2010, 163, 102-109. J. Guo, R. I. Duclos, Jr., V. Kiran Vemuri, A. Makriyannis, "The conformations of 17estradiol (E2) and 17-estradiol as determined by solution NMR," Tetrahedron Lett. 2010, 51, 3465-3469. R. I. Duclos, Jr., M. Johnston, S. K. Vadivel, A. Makriyannis, S. T. Glaser, S. J. Gatley, "A methodology for radiolabeling of the endocannabinoid 2-arachidonoylglycerol (2-AG)," J. Org. Chem. 2011, 76, 2049-2055. M. Johnston, S. R. Bhatt, S. Sikka, R. W. Mercier, J. M. West, A. Makriyannis, S. J. Gatley, R. I. Duclos, Jr. "Assay and Inhibition of Diacylglycerol Lipase Activity," Bioorg. Med. Chem. Lett. 2012, 22, 4585-4592. R. I. Duclos, Jr., X. Li, M. Carraway, H. Herscovitz, A. Gulati, W. Qiu, G. G. Shipley, "Expression and purification of the extracellular domains of the human low density lipoprotein receptor," (manuscript in preparation). Summary: 3 reviews, 31 research papers published in peer-reviewed journals (7 as the corresponding author as of July 2012) Richard I. Duclos, Jr., Ph.D. (curriculum vitae, page 5 of 6) ABSTRACTS AND PRESENTATIONS R. I. Duclos, Jr., O. H. Abdelmageed and A. Makriyannis, "New Antineoplastic Phospholipids: Novel Analogs of 2-O-Methyl-1-O-octadecyl-glycero-3phosphocholine (ET-18-OCH3)," Fourteenth New England Regional Medicinal Chemistry and Pharmacognosy Meeting, Ashland, Massachusetts, April 28-29, 1989. F. S. Hing, R. I. Duclos, Jr. and G. G. Shipley, "Structural effects of chain linkage in phosphatidylcholine bilayers," 1992 ASBMB / Biophysical Society Meeting, Houston, Texas, February 9-13, 1992. Biophys. J. 1992, 61, A502 (Abstract 2898). G. G. Shipley, R. I. Duclos, Jr. and J. Shah, "X-Ray diffraction and calorimetric studies of 1-stearoyl-2-acetyl-phosphatidylcholine," 1992 ASBMB / Biophysical Society Meeting, Houston, Texas, February 9-13, 1992. Biophys. J. 1992, 61, A503 (Abstract 2900). R. I. Duclos, Jr., "Syntheses of Lipids," R. T. Major Symposium, University of Connecticut, Department of Chemistry, Storrs, Connecticut, October 27-29, 1993. R. I. Duclos, Jr., "Syntheses and Biological Activities of Naturally Occurring Lipids and Some Unnatural Lipid Analogs," University of New Hampshire, Department of Chemistry Seminar, Durham, New Hampshire, May 3, 1994. R. I. Duclos, Jr., "Syntheses and Biological Activities of Naturally Occurring Lipids and Some Unnatural Lipid Analogs," University of Connecticut, School of Pharmacy Special Seminar, Storrs, Connecticut, March 26, 1997. R. I. Duclos, Jr., "Concise synthesis of the glycosphingolipid ganglioside GM3," American Chemical Society, Northeast Regional Section Meeting, University of New Hampshire, Durham, New Hampshire, June 25, 2001. S. J. Gatley, R. I. Duclos, Jr., K. Qian and S. T. Glaser, "Brain transport and metabolism studies with 2-arachidonoylglycerol (2-AG) and fatty acid ethanolamides," 21st Annual Symposium of the International Cannabinoid Research Society, St. Charles, Illinois, July 5-10, 2011. M. K. Pandey, S. J. Gatley, K. Qian, R. I. Duclos, Jr. "Design and synthesis of N-(16[18F]fluorohexadecanoyl)ethanolamide (16FEA) as endocannabinoid PET probe in animals and plants," Society of Nuclear Medicine and Molecular Imaging (SNM) Annual Meeting, Miami Beach Convention Center, Miami, Florida, June 9-13, 2012. PATENTS A. Makriyannis, R. I. Duclos, Jr. and D. J. Fournier, "Phospholipid Compounds and Use Therefor," U. S. Patent 5,489,580, February 6, 1996 (Filed 11/5/92). R. I. Duclos, Jr. and S. J. Gatley, "Novel Diacylglycerol Lipase Inhibitors and Methods of Use Thereof," (Filed 5/24/12). Richard I. Duclos, Jr., Ph.D. (curriculum vitae, page 6 of 6) OTHER SERVICE Ad Hoc Member of NIH NCI (NTROI) Network for Translational Research: Optical Imaging ZCA1 SRRB-9, Meeting dates June 2 & 3, 2008 Reviewer: Bioorganic & Medicinal Chemistry Letters, Journal of Medicinal Chemistry, Chemistry and Physics of Lipids, Biochimica et Biophysica Acta, Journal of Lipid Research, Journal of Organic Chemistry Search Committee Member, Associate Dean of Research for Bouvé College of Health Sciences, Northeastern University, December 2011 - April 2012. RESEARCH SUPPORT 2 P01 DA09158 (PD = A. Makriyannis) 5/15/2007–4/30/12 Endocannabinoid Active Sites as Therapeutic Targets: The major goals of this core project involve: (1) the production of radiolabeled and nonradiolabeled analogs in sufficient quantities to address the needs of the research laboratories involved in the four related projects; (2) the biochemical and pharmacological characterization of these compounds; (3) the development of epitope tagged CB1 and CB2 constructs and their expression in mammalian cells; and, (4) the preparation of antibodies for the CB1 and CB2 receptors. Role: PI of Chemistry/Biochemistry/Cell Biology/Pharmacology Core 1 RO3 DA024842-01 (PD = R. Duclos) 4/01/2008–3/31/10 (NCE to 3/31/11) Inhibition of Endocannabinoid Biosynthesis via Diacylglycerol Lipase: The goal of this research was to develop highly selective bioavailable inhibitors of diacylglycerol lipase, the primary enzyme responsible for the biosynthesis of the endogeneous cannabinoid 2-arachidonoylglycerol, to probe endocannabinoid signaling. Role: PD