Dr. Steve Han_COC 2019

Biography
Prof. Zhengxu (Steve) Han Boehringer Ingelheim Pharmaceuticals Inc., USA
Abstract: Chiral phosphine compounds have been widely used as ligands for transition metal catalysed asymmetric transformation in the synthesis of bioactive molecules or drug substance. Proven evidence has showed that ligand with P-stereogenic chiral center is superior in both reactivity and selectivity. However, among many chiral phosphine ligands used, only a few ligands bear P-stereogenic chiral centers due to the difficulty in their synthesis. Although the prominent P-chiral ligand DIPAMP was prepared by Knowles and co-workers in the 1970s, methods for the synthesis of optically active P-chiral phosphines have emerged slowly and there is no general and effective method for the synthesis. This presentation will focus our many year efforts in designing an efficient and general method in the synthesis of P-chiral phosphine ligands with diverse structure and functionality. The application of these P-chiral ligands in the asymmetric synthesis of active pharmaceutics will also be presented. References: 1. Z. S. Han, H. Wu, Y. Xu, Y. Zhang, B. Qu, Z. Li, D. R. Caldwell, K. R. Fandrick, L. Zhang, F. Roschanger, J. J. Song, C. H. Senanayake, “General and Stereoselective Method for the Synthesis of Sterically Congested and Structurally Diverse P-Stereogenic Secondary Phosphine Oxide”, Org. Lett.2017, 19, 1796-1799. 2. Z.S. Han, N.Goyal, M. A. Herbage, J.D. Sieber, B. Qu, Y. Xu, Z. Li, J.T. Reeves, J.-N. Desrosiers, S. Ma, N. Grinberg, H. Lee, H. P. R. Mangunuru, Y. Zhang, D. Krishnamurthy, B. Z. Lu, J. J.Song,G. Wang, and C. H. Senanayake, J. Am. Chem. Soc. 2013, 135, 2474-2477. 3. Z.S. Han, N.Goyal, M. A. Herbage, H. P. R. Mangunuru, Y. Xu , Z. Zhang, J. T. Reeves, J.D. Sieber, Z. Li, P. DeCroos, Y. Zhang, G. Li, N. Li, S. Ma. N. Grinberg, X. Wang, G. Goyal, D. Krishnamurthy, B. Z. Lu, J. J. Song,G. Wang, and C. H. Senanayake, , Angew. Chem. Int. Ed. 2013, 52,6713 –6717.
Biography: Zhengxu (Steve) Han He received his B.S degree and Ph.D. in organic chemistry from Lanzhou University with Professor You-Cheng Liu. In 1991, he moved to Tübingen University, Germany, as a fellow of the Alexander von Humboldt Foundation with Professor Anton Rieker. After postdoctoral research with Professor Stuart Linn at University California, Berkeley, and Professor Lee Magid at the University of Tennessee, Knoxville, he joined the process research group at Sepracorin 1998 and then Boehringer Ingelheim in 2005. He is now a Senior Research Fellow and his research interest centers on efficient process and methodology development for asymmetric synthesis. LATEST INVITED LECTURES 1. “Efficient asymmetric synthesis of P-stereogenic chiral phosphine ligands and complex drug substances on large scale”, Department of Chemistry, California Institute of Technology, December 12, 2018. 2. “Solve issues from process point of view: Research toward developing general methods for the synthesis of P-stereogenic chiral phosphine compounds and application in the synthesis of complex drug substance via asymmetric catalyst”, Department of Chemistry and Biochemistry, University of California at Los Angela, November 9th, 2017. 3. “Research toward Practical Methods for the Synthesis of P-Stereogenic Chiral Phosphine Ligands and Applications to Asymmetric Synthesis of Drug Substances”, 38th International Conference on Organic Process and Development, Stockholm, Sweden, September 27th -29th, 2017. 4. “Developing efficient processes of complex drug substance via innovative basic research”, 2017 (Ningbo) Pharmaceutical Sciences Forum: Future Opportunities for Collaboration in Research and Talents, University of Nottingham & Ningbo Science and Technology Bureau, Oct. 26th, 2017. 5. “Research toward general and efficient method for the synthesis of P-stereogenic phosphine compounds for organic catalysis”, Department of Chemistry, China East Normal University, Shanghai, May 27, 2016. 6. “Practical synthesis of complex drug substance by innovative design” 2nd International Conference on Organic Chemistry, Nanjing, China, May 30-June 1st, 2016. 7. “Design and Synthesis of Chiral Oxathiozinone Scaffolds: Efficient Synthesis of Hindered Enantiopure Sulfinamides and Their Application to Chiral Amines Synthesis” Pacific Chem. Hawaii, December, 18, 2015. 8. “Effective asymmetric synthesis of complex drug substance on large scale and P-stereogenic chiral phosphine oxide for catalysis”, Department of Chemistry and Biochemistry, McGill University, Montreal, Quebec, Canada, November 6, 2015. 9. “Practical through innovative research: Efficient asymmetric synthesis of chiral sulfonamides and P-chiral compounds for organometallic catalysis”, 34th International Conference on Organic Process and Development, Novotel, Barcelona, Spain, 28th – 30th September 2015. 10. “ Efficient asymmetric synthesis of complex substrate on large scale”, The 4th International Symposium on Organic Synthesis and Drug Discovery, Xuzhou, China, May, 23-25th, 2014. 11. “Practical Process Development for Enantioselective Synthesis of Complex CETP Inhibitor”, Scientific Update on Process Research and Development, Lisbon Portugal, Sepember 25-27, 2013.11. “Novel Method Development for Efficient Asymmetric Synthesis of Chiral Sulfinamides”, Chiral Europe, Prague, Czech Republic, September 23-25, 2012. 12. “Method development efficient asymmetric synthesis of chiral sulfur compounds for asymmetric synthesis of chiral amines”, Department of Chemistry, University of New Olean, August, 2011.

Biography

Prof. Zhengxu (Steve) Han
Boehringer Ingelheim Pharmaceuticals Inc., USA

Abstract:

Chiral phosphine compounds have been widely used as ligands for transition metal catalysed asymmetric transformation in the synthesis of bioactive molecules or drug substance. Proven evidence has showed that ligand with P-stereogenic chiral center is superior in both reactivity and selectivity. However, among many chiral phosphine ligands used, only a few ligands bear P-stereogenic chiral centers due to the difficulty in their synthesis. Although the prominent P-chiral ligand DIPAMP was prepared by Knowles and co-workers in the 1970s, methods for the synthesis of optically active P-chiral phosphines have emerged slowly and there is no general and effective method for the synthesis. This presentation will focus our many year efforts in designing an efficient and general method in the synthesis of P-chiral phosphine ligands with diverse structure and functionality. The application of these P-chiral ligands in the asymmetric synthesis of active pharmaceutics will also be presented.

图片简称

References:

1. Z. S. Han, H. Wu, Y. Xu, Y. Zhang, B. Qu, Z. Li, D. R. Caldwell, K. R. Fandrick, L. Zhang, F. Roschanger, J. J. Song, C. H. Senanayake, “General and Stereoselective Method for the Synthesis of Sterically Congested and Structurally Diverse P-Stereogenic Secondary Phosphine Oxide”, Org. Lett.2017, 19, 1796-1799.

2. Z.S. Han, N.Goyal, M. A. Herbage, J.D. Sieber, B. Qu, Y. Xu, Z. Li, J.T. Reeves, J.-N. Desrosiers, S. Ma, N. Grinberg, H. Lee, H. P. R. Mangunuru, Y. Zhang, D. Krishnamurthy, B. Z. Lu, J. J.Song,G. Wang, and C. H. Senanayake, J. Am. Chem. Soc. 2013, 135, 2474-2477.

3. Z.S. Han, N.Goyal, M. A. Herbage, H. P. R. Mangunuru, Y. Xu , Z. Zhang, J. T. Reeves, J.D. Sieber, Z. Li, P. DeCroos, Y. Zhang, G. Li, N. Li, S. Ma. N. Grinberg, X. Wang, G. Goyal, D. Krishnamurthy, B. Z. Lu, J. J. Song,G. Wang, and C. H. Senanayake, , Angew. Chem. Int. Ed. 2013, 52,6713 –6717.

Biography:

Zhengxu (Steve) Han He received his B.S degree and Ph.D. in organic chemistry from Lanzhou University with Professor You-Cheng Liu. In 1991, he moved to Tübingen University, Germany, as a fellow of the Alexander von Humboldt Foundation with Professor Anton Rieker. After postdoctoral research with Professor Stuart Linn at University California, Berkeley, and Professor Lee Magid at the University of Tennessee, Knoxville, he joined the process research group at Sepracorin 1998 and then Boehringer Ingelheim in 2005. He is now a Senior Research Fellow and his research interest centers on efficient process and methodology development for asymmetric synthesis.

LATEST INVITED LECTURES

1. “Efficient asymmetric synthesis of P-stereogenic chiral phosphine ligands and complex drug substances on large scale”, Department of Chemistry, California Institute of Technology, December 12, 2018.

2. “Solve issues from process point of view: Research toward developing general methods for the synthesis of P-stereogenic chiral phosphine compounds and application in the synthesis of complex drug substance via asymmetric catalyst”, Department of Chemistry and Biochemistry, University of California at Los Angela, November 9th, 2017.

3. “Research toward Practical Methods for the Synthesis of P-Stereogenic Chiral Phosphine Ligands and Applications to Asymmetric Synthesis of Drug Substances”, 38th International Conference on Organic Process and Development, Stockholm, Sweden, September 27th -29th, 2017.

4. “Developing efficient processes of complex drug substance via innovative basic research”, 2017 (Ningbo) Pharmaceutical Sciences Forum: Future Opportunities for Collaboration in Research and Talents, University of Nottingham & Ningbo Science and Technology Bureau, Oct. 26th, 2017.

5. “Research toward general and efficient method for the synthesis of P-stereogenic phosphine compounds for organic catalysis”, Department of Chemistry, China East Normal University, Shanghai, May 27, 2016.

6. “Practical synthesis of complex drug substance by innovative design” 2nd International Conference on Organic Chemistry, Nanjing, China, May 30-June 1st, 2016.

7. “Design and Synthesis of Chiral Oxathiozinone Scaffolds: Efficient Synthesis of Hindered Enantiopure Sulfinamides and Their Application to Chiral Amines Synthesis” Pacific Chem. Hawaii, December, 18, 2015.

8. “Effective asymmetric synthesis of complex drug substance on large scale and P-stereogenic chiral phosphine oxide for catalysis”, Department of Chemistry and Biochemistry, McGill University, Montreal, Quebec, Canada, November 6, 2015.

9. “Practical through innovative research: Efficient asymmetric synthesis of chiral sulfonamides and P-chiral compounds for organometallic catalysis”, 34th International Conference on Organic Process and Development, Novotel, Barcelona, Spain, 28th – 30th September 2015.

10. “ Efficient asymmetric synthesis of complex substrate on large scale”, The 4th International Symposium on Organic Synthesis and Drug Discovery, Xuzhou, China, May, 23-25th, 2014.

11. “Practical Process Development for Enantioselective Synthesis of Complex CETP Inhibitor”, Scientific Update on Process Research and Development, Lisbon Portugal, Sepember 25-27, 2013.11. “Novel Method Development for Efficient Asymmetric Synthesis of Chiral Sulfinamides”, Chiral Europe, Prague, Czech Republic, September 23-25, 2012.

12. “Method development efficient asymmetric synthesis of chiral sulfur compounds for asymmetric synthesis of chiral amines”, Department of Chemistry, University of New Olean, August, 2011.