Zhendong Jin

Zhendong Jin

  • Professor, Department of Pharmaceutical Sciences and Experimental Therapeutics / Division of Medicinal and Natural Products Chemistry

Research Narrative

The main emphasis of Dr. Jin’s research is the total synthesis of various biologically active natural products and structural analogues, the discovery and development of new synthetic methods with particular interest in asymmetric reactions, and synthesis of novel anticancer agents.

Curriculum vitae

Education
PhD Chemistry, Purdue University (under the guidance of Prof. Philip L. Fuchs), 1995

Professional Experience
NIH Postdoctoral Fellow
1996-1997, The Scripps Research Institute, (w/ Prof. K. C. Nicolaou)
1997-2003, University of Iowa, College of Pharmacy, Assistant Professor
2003-present, University of Iowa, College of Pharmacy, Associate Professor

Research

Our research lies at the interface of chemistry and the biology of medicinally important natural products. In the past ten years, we have shifted our research emphasis from total synthesis to the development of the next generation of anticancer drugs against aggressive cancers lacking effective drug therapy. We have successfully developed innovative natural products-inspired drug development technology with the following important features:

  • Inspired by unique chemical structures of some highly potent anticancer natural products, we design structurally simplified lead compounds that maintain their potent anticancer activity.
  • Develop a compressive synthetic approach with the following important features:
    • Can be readily scaled up
    • Readily structural modifications at key positions of the molecule for medicinal chemistry study
    • Can be modified for the synthesis of various molecular probes for drug target identification and chemical biology investigation
    • Have handles at suitable positions for potential bioconjugation and drug delivery study
  • Highly efficient lead optimization with pinpoint accuracy
  • Some compounds that are synthesized in our medicinal chemistry study may have other important applications such as payloads for antibody-drug conjugates (ADCs) and small-molecule drug conjugates. Using our technology we have successfully advanced two very promising 1st-in-class anticancer drug candidates (inspired by natural products OSW-1 and superstolide A) to preclinical evaluation. In addition, we have developed a group of novel cytotoxic payloads for antibody-drug conjugates (ADCs).

Using our technology we have successfully advanced two very promising 1st-in-class anticancer drug candidates (inspired by natural products OSW-1 and superstolide A) to preclinical evaluation. In addition, we have developed a group of novel cytotoxic payloads for antibody-drug conjugates (ADCs).

Representative Publications

Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: a role played by the lactone moiety, Qiu, H.; Qian, S.; Head, S. A.; Liu, J. O.; Jin, Z. Bioorg. Med. Chem. Lett. 2016, 26, 4702.

Insights into the Structure-activity Relationship of the Anticancer Compound ZJ-101, A Derivative of Marine Natural Product Superstolide A: A Critical Role Played by the Conjugated Trienyl Lactone Moiety, Qian, S.; Shah, A. K.; Head, S. A.; Liu, J. O.; Jin, Z. Bioorg. Med. Chem. Lett. 2016, 26, 3411.

Insights into the Structure-activity Relationship of the Anticancer Compound ZJ-101: A Critical Role Played by the Cyclohexene Ring, Shah, A. K.; Qian, S.; Head, S. A.; Liu, J. O.; Jin, Z. Bioorg. Med. Chem. Lett. 2016, 26, 2890.

Regioselective Spirostan E-Ring Opening for the Synthesis of Dihydropyran Steroidal Frameworks, Hilario-Martínez, J. C.; Zeferino-Díaz, R.; Muñoz-Hernández, M. A.; Hernández-Linares, M. G.; Cabellos, J. L., Merino, G.; Sandoval-Ramírez, J. Jin, Z.; Fernández-Herrera; M. A. Org. Lett. 2016, 18, 1772.

Decreased Ferroportin Promotes Myeloma Cell Growth and Osteoclast Differentiation, Zhimin Gu, He Wang, Jiliang Xia, YE YANG, Junwei Huang, Zhendong Jin, Hongwei Xu, Jumei Shi, Guido Tricot, and Fenghuang Zhan. Cancer Research 2015, 75, 2211.

Jin, Z., Shah, A. K. Encyclopaedia of Reagents for Organic Synthesis. John Wiley & Sons, Ltd.

Garcia-Prieto C, Riaz Ahmed KB, Chen Z, Zhou Y, Hammoudi N, Kang Y, Lou C, Mei Y, Jin Z, Huang P. 2013. Effective Killing of Leukemia Cells by the Natural Product OSW-1 through Disruption of Cellular Calcium Homeostasis. J. Biol. Chem. 288, 3240.

Chen L, Riaz Ahmed KB, Huang P, Jin Z.  2013. Design, Synthesis and Biological Evaluation of Truncated Superstolide A. Angewandte Chemie Int. Ed. 52, 3446.

Chen, L., Hua, Z., Li, G., Jin, Z. 2011. Controlling the Facial Selectivity of Asymmetric [4+2] Cycloadditions: A Concise Synthesis of the cis-Decalin Core Structure of Superstolides A and B, Org. Lett. 13, 3580.

Jin, Z., Zhang, Z. 2010. Cyanotrimethylsilane. Encyclopaedia of Reagents for Organic Synthesis. John Wiley & Sons, Ltd.

Kang, Y., Lou, C., Ahmed, K. B. R., Huang, P., Jin, Z. 2009. Synthesis of a Biotinylated-OSW-1. Bioorg. Med. Chem. Lett. 19, 5166.

Hua, Z., Chen, L., Jin, Z. 2009. Asymmetric [4+2] Cycloadditions Employing 1,3-Dienes Derived from Chiral 4-Hydroxy-2-cyclohexenone. Tetrahedron Lett. 50, 6621.

Lou, C., Jin, Z. 2005. Ethoxyacetylene. Encyclopaedia of Reagents for Organic Synthesis. John Wiley & Sons, Ltd.

Zhou, Y., Garcia-Prieto, C., Carney, D., Xu, R., Pelicano, H., Kang, Y., Yu, W., Lou, C., Kondo, S., Liu, J., Harris, D., Estrov, Z., Keating, M. J., Jin, Z., Huang, P. 2005. OSW-1: A Natural Compound with Potent Anticancer Activity and Novel Mechanism of Action. Journal of the National Cancer Institute, 97, 1781.

Hua, Z., Yu, W., Su, M., Jin, Z. 2005. Synthetic Studies toward the Construction of the cis-Decalin Portion of Superstolides A and B. Application of a Sequential Double Michael Reaction and an Anionic Oxy-Cope Rearrangement. Org. Lett. 7, 1939.

Gao, X., Yu, W., Mei, Yan, Jin, Z. 2004. Heck Reaction with an Acyl Synthon: New Coupling Reaction between α-Halo Vinyl Ether and Alkene. Tetrahedron Lett. 45, 8169.

Hua, Z., Yu, W., Jin, Z. 2004. An Improved Procedure for the Oxidative Cleavage of Olefins by OsO4-NaIO4. Org. Lett. 6, 3217.

Kang, Y., Mei, Y., Du, Y., Jin, Z. 2003. Total Syntheses of the Highly Potent anti-HIV Natural Product Daurichromenic Acid and its Two Novel Chromene Derivatives, Rhododaurichromanic Acids A and B. Org. Lett. 5, 4481.

Yu, W., Jin, Z. 2002. Total Synthesis of An Antitumor Natural Product OSW-1. J. Am. Chem. Soc. 124, 6576.

Su, M., Kang, Y., Yu, W., Hua, Z., Jin, Z. 2002. Negishi Coupling between a-Alkyl(aryl)thio Vinyl Zinc Chloride and α-Bromo Vinyl Ether: a Convergent Synthesis of 2-Alkoxy-3-alkyl(aryl)thiobuta-1,3-dienes. Org. Lett. 4, 691.

Su, M., Yu, W., Jin, Z. 2001. A Highly Stereoselective Synthesis of a-Halo Vinyl Sulfides and Their Applications in Organic Synthesis. Tetrahedron Lett. 42, 3771.

Yu, W., Zhang, Y., Jin. Z. 2001. Synthetic Studies of Antitumor Marine Natural Products Superstolides A and B. Construction of C20-C26 Fragment of Superstolide A, Org. Lett. 3, 1447.

Yu, W., Jin, Z. 2001. A New Strategy for the Stereoselective Introduction of Steroid Side Chain via α-Alkoxy Vinyl Cuprates: Total Synthesis of a Highly Potent Antitumor Natural Product OSW-1, J. Am. Chem. Soc. 123, 3369.

Yu, W., Jin, Z. 2001. A Facile Generation of Enolates from Silyl Enol Ethers by Potassium Ethoxide. Tetrahedron Lett. 42, 369.

Yu, W., Jin, Z. 2000. A Facile Stereospecific Synthesis of α-Halo Vinyl Ethers and Their Applications in Organic Synthesis. J. Am. Chem. Soc. 122, 9840.

Yu, W., Su, M., Gao, X., Yang, Z., Jin, Z. 2000. A Facile Chemoselective Deprotection of p-Methoxybenzyl Group. Tetrahedron Lett. 41, 4015.

Yu, W., Su, M., Jin, Z. 1999, A Highly Selective Synthesis of (Z)-α,β-Unsaturated Ketones. Tetrahedron Lett. 40, 6725.

Patents Filed

Therapeutic compounds, Zhendong Jin and Lei Chen. US patent No. 9,346,781. Japan patent No. 6289463. EP patent has been approved. International application number: PCT/US13/052081. International patent applications covering Australia, Canada, Japan, Korea, China, Brazil, Israel, Mexico, and India.

Therapeutic compounds, Zhendong Jin, Aashay K. Shah, Lei Chen, and Yan Mei, patent application (US 61/264,056, PCT/US2016/065059).

Total synthesis of OSW-1, Zhendong Jin, Wensheng Yu, Provisional Patent Application No.60/310,709.

Total Synthesis of the Highly Potent anti-HIV Natural Product Daurichromenic Acid along with Its Two Chromane Derivatives, Rhododaurichromanic Acids A and B, Ying Kang, Yan Mei, Zhendong Jin.

The Use of Orsaponin [3ß,16ß,17α-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxy-benzoyl-ß-D-xylopyranosyl)-(13)-(2-O-acetyl-α-L-arabinopyranoside)] and Its Derivatives for Cancer Therapeutics, Peng Huang, Michael J. Keating, Zhendong Jin.