Zhiqiang Xia

*** ************* ******, *****, ************* 01720

978-***-****[H] 978-***-****[C] ie1pbw@r.postjobfree.com

Summary

Synthetic Organic Chemist with 12 years of experience in pharmaceutical industry, organic synthesis and process chemistry. Creative and highly motivated scientist with a strong track record of achievements in organic and medicinal chemistry. Expertise in problem solving in organic synthesis and scale up. Synthesized and developed Elesclomol, a novel small molecular anti-cancer drug candidate in clinic trial. Designed and synthesized ion channel inhibitors that demonstrated strong anti-inflammation activity in preclinical studies. Excellent at design and synthesis of novel lead compounds, employing SAR for lead optimization. Extensive experience in organic synthesis and process chemistry.

Experience

Synta Pharmaceuticals, Lexington, MA 07/2000-02/2012

Principal Scientist, Department of Chemistry (04/2011-02/2012)

Designed and synthesized a novel series CRAC (calcium release-activated calcium) channel inhibitors (small molecular compounds) that demonstrated strong anti-inflammation activity in preclinical studies.

Cooperated with scientists of DMPK, biology and toxicology departments for lead optimization.

Scale up lead compounds and reaction optimizations (~ 20g).

Senior Scientist (04/2004-03/2011)

Designed and synthesized a novel series CRAC channel inhibitors with high potency and good DMPK properties.

Synthesized Elesclomol that applied in clinic trial for cancer treatment.

Designed and synthesized the secondary generation of Elesclomol.

Designed, developed and optimized Elesclomol process. (> 10 kg GMP)

Scientist (07/2000-03/2004)

Designed and synthesized indole-imidazole compounds that demonstrated cytotoxicity against multidrug resistant cancer cell lines, SAR and lead optimization.

Designed and synthesized STA-5312, a novel indolizine oxalylamide microtubule inhibitor.

STA-5312 process development. (> 5 kg)

Designed and synthesized dihydropyridine compounds for metabolic disorder treatment. (lead scale up 1 kg)

Institute of Biological Chemistry, Washington State University, Pullman, WA 06/1994-06/2000

Research Scientist

Designed and synthesized complex plant phenols, e.g. podophyllotoxin, pinoesinol, matairesinol, dehydrodiconiferyl alcohol.

Elucidated the biochemical pathway to the anti-cancer lignan podophyllotoxin.

Isolated and purified plant phenols from various plant species. Identified metabolites present in Hedychium gardnerneranum plant extracts.

Isotope labeling of various plant phenol precursors.

Custom synthesis of a chlorinated hydroxyfuranone.

Purified secoisolariciresinol dehydrogenase.

Department of Chemistry, University of Oulu, Finland 09/1993-05/1994

Visiting Scientist

Established a new synthetic route for taxol C-ring. The optically pure precursor was obtained by asymmetric synthesis.

Institute für Pharmazeutische Biologie, Technishe Universität, Brauschweig, Germany 01/1993-08/1993

Visiting Scientist

Designed and synthesized trachlanthamidine, an intermediate of pyrrolizidine alkaloid.

Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China 07/1988-12/1990

Assistant Professor

Designed and synthesized the intermediates of arteannuin.

Elucidated the biochemical pathway to antimalarial drug Arteanuin.

Isolated and identified of 11R- -dihydroarteanuic acid from Artemisia annua, a key intermediate of arteannuin.

Education

Humboldt Fellowship, Pharmazeutishe Biologie, Universität Müchen, Germany (01/1991-12/1992)

Designed and synthesized plant growth regulator jasmonates and their derivatives.

Elucidated the biochemical pathway to indigo precursors in higher plants.

Investigated the metabolism of jasmonic acid in suspension cultures of Eschshcoltzia.

Ph.D., Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China (1988)

B.Sc., Organic Chemistry, Wuhan University, Wuhan, China (1982)

Awards

Galactic Halo Award (2011)

Supernova Award - the highest ranked prize at Synta Pharmaceuticals (2004)

Publications

1. Chen, S.; Xia, Z. Q.; Nagai, M; Lu, R.; Kostik, E.; Przewloka, T.; Song, M.; Chimmanamada, D.; James, D.; Zhang, S.; Jiang, J.; Ono, M.; Koya, K.; Sun, L. 2011 Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): Structure-activity relationship Medicinal Chemistry Communications 2 176.

2. James, D.; Koya, K.; Li, H.; Liang, G.; Xia, Z. Q.; Ying, W.; Wu, Y.; Sun, L. 2008 Indole and indolizine-glyoxylamides displaying cytotoxicity against multidrug resistant cancer cell lines. Bioorganic & Medicinal Chemistry Letters 18(6): 1784.

3. Prewloka, T.; Chen, S.; Xia, Z.Q.; Li, H.; Zhang, S.; Chimmanamada, D.; Kostik,E.; David, J.; Koya, K.; Sun, L. 2007 Application of DMF-methyl sulfate adduct in the regioselective synthesis of 3-acylated indolizines Tetrahedron Letters 48(33): 5739.

4. Xia, Z.Q.; Przewloka, T.; Koya, K.; Ono, M. Chen, S.; Sun, L. 2006 Controlling chemoselectivity-application of DMF di-t-butyl acetal in the regioselective synthesis of 3-monosubstituted indolizines Tetrahedron Letters 47(50):8817.

5. Li, H.; Xia, Z.Q. ; Chen, S.; Koya, K.; Ono, M. 2007 Development of a practical synthesis of STA-5312, a novel indolizine oxalylamide microtubule inhibitor Org. Process Res. Dev. 11(2):246.

6. James, D.; Koya, K.; Hao, L.; Chen, S.; Xia, Z.Q.; Ying, W.; Wu, Y.; Sun, L. Conjugated indole-imidazole derivatives displaying cytotoxicity against multidrug resistant cancer cell lines 2006 Bioorganic & Medicinal Chemistry Letters 16(19):5164.

7. Kasahara, H., Jiao, Y., Bedgar, D.L., Kim, S.-J., Patten, A.M., Xia, Z.-Q., Davin, L.B. and Lewis, N.G. 2006. Pinus taeda phenylpropenal double-bond reductase: Purification, cDNA cloning, heterologous expression in Escherichia coli, and subcellular localization in P. taeda. Phytochemistry 67(16):1765.

8. Xia, Z.Q.; Costa, M.A.; Pélissier, H.C.;Davin, L.B.; Lewis, N.G. Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. 2001 J. Biol. Chem. 276:12614.

9. Xia, Z.Q.; Costa, M.A ; Proctor, J.:Davin, L.B.; Lewis, N.G. Dirigent-mediated podophylllotoxin biosynthesis in Linun flavum and Podophyllum peltatum. 2000 Phytochemistry 55(6):537.

10. Costa, M.A.; Xia, Z.Q.; Davin, L.B.; Lewis, N.G. 1999 Towards engineering the metabolic pathways of cancer preventing lignans in cereal grains and crops. In “Recent Advances in Phytochemistry” (Romeo, J.T., ed.), Plenum Press, New York, Vol. 33, 67.

11. Gang, D.R.; Kasahara, H.; Xia, Z.Q.; vander Mijnsbrugge, K.; Boerjan, W.; van Montagu, M.;Davin, L.B.; Lewis, N.G. 1999 Evolution of plant defense mechanism. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases. J. Biol. Chem. 274:7516.

12. Blechert, S.; Brodschelm, W.;Holder, S.; Kammerer, L.; Müller, M.; Xia, Z.Q.; Zenk, M.H. 1995 The octadecanoic pathways: Signal molecules for the regulation of secondary pathways. Proc. Natl. Acad. Sci., USA 92:4099.

13. Xia, Z.Q.; Zenk, M.H. 1993 Metabolism of jasmonic acid in suspension cultures of Eschshotzia. Planta Med. 59(6):575.

14. Weiler, E.W.; Albrecht, T.; Groth, B.; Xia, Z.Q.; Luxem, M.; Liss, H.; Andert, L.;Spengler, P. 1993 Evidence for the involvement of jasmonates and their octadecanoid precursors in the tendril coiling response of Bryonnia dioica. Phytochemistry 32:591.

15. Wang, Y.; Xia, Z.Q.; Zhou, F.Y.; Wu, Y.L.; Huang, J.J; Wang, Z.Z. 1993 Studies on the biosynthesis of arteannuin. IV. The biosynthesis of arteannuin and arteannuin B in Artemisia annua L. Chin. J. Chem. 11(5):457.

16. Wang, Y.; Shen, Z.; Xia, Z.Q.;Zhou, F. 1993 Studies on the biosynthesis of arteannuin. V. The role of 6-epideoxyarteannuin B in biosynthesis of arteannuin. Chin. J. Chem. 11(5):476.

17. Xia, Z.Q.; Zenk, M.H. 1992 Biosynthesis of indigo precursors in higher plants. Phytochemistry 31:2695.

18. Xia, Z.Q.; Huang, J.J.; Wang, Y 1991 Studies on the biosynthesis of arteannuin H. The chemical synthesis of the precursors [15-2H] and [15-3H]-arteanuic acid. Acta Chin. Sin. 49:1514.

19. Wang, Y.; Xia, Z.Q.; Zhou, F.Y.; Wu, Y.L.; Wang, Z.Z. 1988 Studies on the biosynthesis of arteannuin III. Arteannuic acid as a key intermediate in the biosynthesis of arteannuin and arteannuin B. Acta Chim. Sin. (English Edition):386.

20. Huang, J.J.; Xia, Z.Q.; Wu, L.F. 1987 Studies on the constituents of Artemisia annua L. I. The isolation and identification of 11R- -dihydroarteanuic acid. Acta Chim. Sin. 45:609.

Patents

1. Bohnert, G.; Xia, Z. Q.; Chen, S; Sun, L. Preparation of tetrahydropyridine derivatives as inhibitors of proinflammatory cytokine production and CRAC ion channels for treating inflammation and immune disorders. PCT Int. Appl. WO 201******* 4 Aug. 2010.

2. Chen, S; Zhang, J; Jiang, J.; Bohnert, G.; Vo, N.; Che, Q.; Xia, Z. Q.; Sun, L. Preparation of heteroaryl compounds as inhibitors of proinflammatory cytokine production and CRAC ion channels for treating inflammation and immune disorders. PCT Int. Appl. WO 201******* 4. Aug. 2010.

3. Chen, S.; Xia, Z.Q. Kostik, E.; Koya, K.; Sun, L. Purification of bis(thiohydrazide amides) US Pat Appl. Publ. WO 201********-** Jan. 2010.

4. Chen, S.; Sun, L.; Xia, Z. Q.; Koya, K.; Ono, M. Synthesis of taxol enhancers US Pat Appl. Publ. 201********-** Jan. 2010.

5. Chen, S.; Koya, K.; Sun, L.;Tatsuta, N.; Xia, Z.Q. Kostik, E.; Vagheti, F.; Liang, G.; Inoue, T. Bis(thio-hydrazide amide) salts for treatment of cancers US Pat Appl. Publ. 200********-** Nov. 2009.

6. Sun, L.; Kostik, E.; Lee, C.; Ramachandran, K.; Xia, Z.Q.; Zhang, S.; Choi, J. Y.; Jiang, J.; Chen, S. Process for preparing of bis (thiohydrazides). PCT Int. Appl. WO 200-***-**** 6 Nov. 2009.

7. Koya, K; Sun, L.; Chen, S.; Tatsuta, N.; Wu, Y.; Ono, M.; Xia, Z.Q. Pacitaxel enhancer compound US Pat Appl. Publ. 200********-** Oct. 2008.

8. Jiang, J.; Xia, Z. Q.; Zhang, J.; Bohnert, G.; Chen, S.; Xie, Y. Preparation of pyridylphenyl benzamides for treatment of inflammation and immune-related conditions. PCT Int.Appl. WO 2007/089904 8 Sept. 2007.

9. Chen, S.; Xia, Z.Q. Synthesis of bis(thiohydrazides) salts PCT Int. Appl. WO 200-***-**** 23 Nov. 2006.

10. Chen, S.; Jiang, J.; Li, H.; James, D.; Dinesh, C.; Christopher, B.; Sun, L.; Xie, Y.; Holmqvist, M.; Mahiou, J.; Xia, Z.Q. Compounds for inflammation and immune related uses PCT Int. Appl. WO 200-***-**** 30 Mar. 2006.

11. Ono, M.; Wada, Y.; Sun, L.; Chen, S.; Prezewloka, T.; Zhang, S.; Borella, C.; Koya, K.; Foley, K.; Xia, Z.Q.; Li, H.; Zhou, D. Dihydropyridine compounds for treating or preventing metabolic disorders PCT Int. Appl. WO 200-***-**** 24 Mar 2005.

12. Xia, Z.Q.; Costa, M.; Davin, L.B.; Lewis, N.G. Recombinant secoisolariciresinol dehydrogenase, and methods of use. PCT Int. Appl. WO 199*******-** April, 1999.

13. Xia, Z.Q.; Karvinen, E.;Koskinen, A. 1996 A method for the preparation of a novel C-ring precursor for taxiods and novel intermediates. PCT Int. Appl. WO 199*******-** Jan., 1996.

Presentations

1. Sun, L.; Chen, S.; Xia, Z. Q.; Ono, M.; Kostik, E.; Przewloka, T.; Chimmanamada, D.; James, D.; Li, H.; Jiang, J.; Nagai, M.; Lu, R.; Wada, Y.; Koya, K.. Novel indolizine compounds as potent inhibitors of phsophodiesterase IV: Syntheses and structure-activity relationship. 236th ACS National Meeting, Philadelphia, PA, United States, August 2008.

2. James, D.; Koya, K.; Li, H.; Chen, S.; Xia, Z. Q.; Ying, W.; Wu, Y.; Sun, L. Discovery of potent indole and indolizine derivatives displaying cytotoxicity against multidrug resistant cancer cell lines. 232nd ACS National Meeting, San Francisco, CA, United States, Sept. 2006.

3. James, D.; Li, H.; Chen, S.; Xia, Z. Q.; Ying, W.; Wu, Y.; Sun, L.; Koya, K.. An SAR study of conjugated indole-imidazole derivatives displaying substantial in vitro antiproliferative activities against cancer cell lines. 229th ACS National Meeting, San Diego, CA, United States, March, 2005.

4. Przewloka, T.; Xia, Z. Q.; Koya, K.; Ono, M.; Sun, L. Regioselective synthesis of 3-substituted indolizines. 228th ACS National Meeting, Philadelphia, PA, United States, August 2004.

5. Sun, L.; Koya, K.; Li, H.; Przewloka, T; James, D.; Chen, S.; Xia, Z. Q.; Liang, G; Tatsuta, N.; Wu, Y.; Zhou, D.; Korbut, T.; Du, Z.; Ono, M.. The discovery of STA-5312: A Novel microtubule inhibitor demonstrating potent in vitro and in vivo antitumor activities against MDR cancers. 228th ACS National Meeting, Philadelphia, PA, United States, August 2004.

6. Sun, L.; Chen, S.; Koya, K.; Xia, Z. Q.; Korbut, T.; Tatsuta, N.; Du, Z.; Liang, G.; Zhou, D.; Ono, M. Synthesis and biological activities of STA-4783: A novel small molecular enhancer for taxol 227th ACS National meeting Anaheim, CA, United States, March 2004.

7. Kasahara, H.; Gang, D. R.; Xia, Z. Q.; Jiao, Y.; Bedgar, D. L.; Davin, L. B.; Lewis, N. G. Non-lignin, non-structural infusions in the Pinaceae: The “abnormal”.lignins of Pinus taeda and Cryptomeria Japonica. Tenth International Symposium on Wood and Pulping Chemistry, Yokohama, Japan, June 1999.

8. Koca, U.; Xia, Z. Q.; Davin, L. B. Lewis, N.G. Defining the biochemical pathway to the antitumor lignan, podophyllotoxin. Annual Meeting of Phytochemical Society of North America, WA, United States, July 1998.

9. Costa, M. A.; Xia, Z. Q.; Ford, J. F.; Wang, H. B.; Gang, D. R.; Davin, L. B.; Lewis, N. G. Formation of cancer-preventing lignans in plants: Engineering their metabolic pathways. Annual Meeting of Phytochemical Society of North America, Pullman, WA, United States, July 1998.

10. Davin, L. B.; Ford, J. L.; Xia, Z. Q.; Costa, M. A.; Jeon, J. H.; Lewis, N. G. Lignans in chemoprevention against the onset of breast and prostate cancers: Origins of the “mammalian” lignans, enterodiol and enterolactone. Third Tannin Conference, Bend, OR, United States, July, 1998.

11. Lewis, N. G.; Gang, D. R.; Chang, M. K.; Burlat, V.; Xia, Z. Q.; Wang, H. B.; Jiao, Y. Bedgar, D. L. Davin, L. B. Lignans, lignins, and abnormal lignins: A biochemical clarification 215th American Chemical Society National Meeting, Dallas, TX, United States, March 1998.

12. Davin, L. B.; Xia, Z. Q.; Costa, M. A.; Fujita, M.; Lewis, N.G. Purification of secoisolariciresinol dehydrogenase Annual Meeting of the American Society of Plant Physiologists, Vancouver, British Columbia, Canada, August 1997.

13. Davin, L. B.; Xia, Z.Q.; Lewis, N. G. Regulation of lignin synthesis. Annual Meeting of the American Society of Plant Physiologists, Charlotte, NC, United States, August 1995.

14. Xia, Z. Q.; Zenk, M.H.; Metabolism of plant growth regulator jasmonate. IUPAC 18th International Symposium on the Chemistry of Natural products, Strasbourg, France, August-September 1992.

15. Huang, J. J.; Xia, Z. Q.; Wang, Y.; A new biosynthetic precursor of the antimalarial terpene compound arteanuin. IUPAC Symposium on Organic Chemistry of Medicinal Natural Products, Shanghai, China, November 1985.

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