Medicinal Chemist

SUMMARY

• Ph.D. in Organic Chemistry.

• Expert in medicinal chemistry with extensive knowledge in drug discovery (bacteria, oncology and CNS), which includes lead generation and optimization to improve ADMET profiles, preclinical development and project strategy development.

• Expert in synthetic organic chemistry including synthetic route design, synthesis of challenging molecules and strong problem-solving ability.

• Managed medicinal chemistry lab and responsible for medicinal chemistry part.

• Co-author of 11 peer-reviewed publications and 1 patent.

• Self-motivated, results-oriented, strong work ethic with solid organization skill and leadership, strong independent researcher as well as excellent team player.

EXPERIENCES

Project Scientist, Cleveland Clinic, Cleveland, OH, 2010-present

Responsible for medicinal chemistry and provide compounds for biological studies.

CNS Therapeutic Area

• Solved the synthesis of selective potential CB2 agonist MDA104 with chiral quaternary carbon center. MDA104 was obtained from 3-hydroxy-4-iodo benzoic acid in 9 steps in 97.4% ee and 3.4% total yield, which involved palladium catalyzed tandem intramolecular Heck/Suzuki cross coupling reaction, chemical resolution with (+)-norephedrine and Wolf-Kishner reaction as the key steps.

• Lead the effort on the optimization of lead compound of CB2 agonist to improve its ADMET profiles.

Senior Research Scientist, BetaPharma Inc, Branford, CT, 2009-2010

Oncology Therapeutic Area

• EGFR Inhibitor project-Developed back-up candidates for EGFR inhibitor.

Research Scientist, Rib-X Pharmaceutical Company, New Haven, CT, 2005-2009

Antibacterial Therapeutic Area

• Process Chemistry Project- Developed novel methodology for the synthesis of triazole moiety for the process in the construction of RX-2 lead compound and scaled up key intermediates.

• Macrolide Project (targeting MRSA bacteria) – Designed and discovered a series of macrolide compounds ( for example, five-membered cyclic sulfone derivatives) with good properties through lead optimization. Interacted closely with computational chemists and biologists. Scaled up RX-4812, a lead compound for hERG, toxicity and preclinical studies. Supervised a M.S. student.

• P-site Project (targeting gram-negative bacteria)-Involved in the initiation and development of project strategies. Interacted closely with structure-based drug design group and biologists in the process. Independently designed and synthesized novel nucleobase types of scaffold targeting gram-negative bacteria. These include SAR analysis, structure-based drug design, methodology development and multi-step chiral synthesis of designed molecules. Nature product Tan1057A was modified to give good activities against E. Coli. Identified novel lead compounds which were further optimized to give compounds with good activities against gram-negative bacteria.

Postdoctoral Fellow with Professor Gary A. Sulikowski, Texas A& M University and Vanderbilt University, 2001-2005

• Studies on Biomimetic Synthesis of Phomoidride B

Synthesized appropriate precursors in multi-step reaction sequences for biomimetic synthesis of complex natural product Phomoidride B.

• Total Synthesis of the Marine Alkaloid: Upenamide

Developed novel methodology for the construction of core units of upenamide. Among the technologies developed in this synthesis are the use of β-Iodoenecarbamates as starting material to construct the DE hemiaminal fragment via a remarkably stereoselective cyclization. In addition, a stereoselective Diels-Alder reaction coupled with a unique intra-molecular Staudinger reductive cyclization were employed to construct the BC spriocyclic fragment. Finally, a substrate-controlled stereoselective aldol reaction and intramolecular Sonogashira coupling reaction were used to couple DE and BC fragments. This synthesis involves long multi-step synthesis (20 steps), X-ray and 2D-NMR analysis of intermediates and trouble-shooting.

Doctoral Fellow with Prof. Alan R. Katritzky, University of Florida, 1997-2001

• Novel Method Development for Heterocycle Synthesis

Developed tandem reactions for stereoselective synthesis of heterocycles: 1) Iminium ion initiated Mannich-type addition/cyclization reactions were applied in the synthesis of 4-substituted, 3,4-trans substituted and bicyclic piperidines; 2) 2,3-substituted piperidines were obtained from SmI2-mediated 6-exo radical cyclization / anionic reactions; 3) Anionic addition/cyclization reactions followed by nucleophilic substitutions were utilized to prepare 3,4-trans-substituted imidazolidinones; 4) Intramolecular anionic cyclization followed by nucleophilic substitutions gave 2-substituted pyrrolidines. SmI2-induced rearrangement was discovered. 2D-NMR was used to study the conformation and X-ray analysis was used to determine the structure.

Research Associate with Prof. Weisheng Tian, Shanghai Institute of Organic Chemistry, 1995-1997

• Asymmetric Synthesis of Neoclausenamide

An intramolecular nucleophilic substitution of carbon anion to cyclic sulfate was first employed in the asymmetric synthesis of (+)-(3R, 4S, 5R, 7S)-neclausenamide, a novel potential drug for treatment of Alzheimer’s disease.

• Synthesis of compounds for Monsanto companies

Synthesized compounds for Monsanto companies for bioactivity studies.

Research Assistant with Prof. Zhiyu Liu, Shanghai Institute of Organic Chemistry, 1992-1995

• Synthesis of Taxol and Steroid Analogues

EDUCATION

Ph.D. in Organic Chemistry, University of Florida, Gainesville, FL, 2001

Advisor: Professor Alan R Katritzky

M.Sc. in Organic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai, China, 1995

Advisor: Professor Zhiyu Liu

B. Sc. in Chemistry, Peking University, Beijing, China, 1992

PUBLICATIONS

Luo,Z., Naguib, M. “ A Synthetic Approach for MDA104, A Selective CB2 Agonist” Tetrahedron Lett.

2012, submitted.

Luo, Z.; Peplowski, K.; Sulikowski, G. A. “Formation of the BC Ring of Upenamide via a Staudinger/Aza Wittig Reaction” Org. Lett. 2007, 9, 5051.

Kiewel, K.; Luo, Z.; Sulikowski, G. A. “Stereocontrolled Synthesis of the DE Ring System of the Marine Alkaloid Upenamide” Org. Lett. 2005, 7, 5163.

Sulikowski, G. A.; Liu, W.; Luo, Z.; Agnelli, F.; Corbett, R.M; Hershberger, S. J. “Progress toward a Biomimetic Synthesis of Phomoidride B ” Org. Lett. 2002, 4, 1451.

Katritzky, A. R.; Luo, Z. “Remarkably Easy Oxidation of Alkylzinc Reagents in Their Reactions with Electrophiles to Produce Alkoxylated instead of Expected Alkylated Products” Heterocycles 2001, 55, 1467.

Katritzky, A. R.; Luo, Z.; Fang, Y., “N-Boc-N-(benzotriazol-1-ylmethyl) benzylamine as a 1,1-Dipole Equivalent in Stereoselective Synthesis of 4,5-Disubstituted Imidazolidin-2-ones”, J. Org. Chem. 2001, 66, 2858.

Katritzky, A. R.; Luo, Z.; Fang, Y., “A Facile Route to 2-Substituted Pyrrolidines”, Tetrahedron Lett. 2000, 41, 9691-9693.

Katritzky, A. R.; Luo, Z.; Fang, Y.; Feng, D., “Preparation of Polysubstituted Piperidines via Radical Cyclizations” J. Chem. Soc., Perkin Trans. 2 2000, 7, 1375.

Katritzky, A. R.; Luo, Z.; Cui, X. L., “Synthesis of Substituted Piperidines from N,N-Bi[(benzotriazole-1-yl)methyl]amines”, J. Org. Chem.1999, 64, 3328.

Wang, J.; Luo, Z.; Tian, W., “A New Asymmetric Synthesis of (+)-(3R, 4S, 5R, 7S)-Neoclausenamide via Intra-molecular Nucleophilic Substitution of Carbon Anion to Cyclic Sulfate”, Chinese Chemical Letter 1997, 8, 281.

Liu, Z.; Fan, T.; Zhu, X.; Luo, Z.; Cheng, W., “A Stereospecific Synthesis of the Taxol Side Chain Acetonide”, Acta Chim. Sinica 1997, 55, 824.

PATENTS

Bhattacharjee, Ashoke; Du, Yanming; Duffy, Erin, M. ; Job, Gabriel, E. ; Lou, Rongliang; Luo, Zhushou; O'dowd, Hardwin; Tang, Yuanqing; WU, Yusheng “Macrolide Compounds and Methods of Making and Using the Same” PCT Int. Appl.(2008) WO2008106224

CONFERENCES AND PRESENTATIONS

10th International Conference on the Chemistry of Antibiotics and Other Bioactive Compounds, Nashville, TN, 2007.

228th ACS national meeting, Philadelphia, PA.“Progress toward the Total Synthesis of Upenamide”, 2004.

220th ACS meeting in Washington, DC. “N-Boc-N-(benzotriazol-1-ylmethyl) benzylamine as a 1,1-Dipole Equivalent in Stereo-selective Synthesis of 4,5-Disubstituted Imidazolidin-2-ones ”, 2000.

REFERENCES

Available upon request

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