Bioactive natural products and their total syntheses play a critical role in drug discovery. Our research interests involve around the total syntheses of anticancer natural products and their analogues, including biological evaluation studies for their potencies. This will entail: 1. development and streamlining of a successful route for the total syntheses of the targeted natural products and designed  analogues; 2. biological evaluation of the synthesized analogues for structure–activity relationship studies, including in silco investigations (e.g., molecular docking for analogue optimization); and 3. advancing promising analogues to linker-drugs and eventually antibody–drug conjugates. In collaboration with structural and computational biologist, and pharmacologist in iHuman institute, we will investigate the mechanism of the interaction between the synthesized natural product analogues and the targeted enzymes or receptors, which may lead to success in translating such an analogue first to a lead compound and then hopefully after additional optimization to a drug candidate.

In recent years, Dr. Saiyong Pan have developed several novel strategies and synthetic methods and technologies to solve synthetic efficacy problems in the total synthesis area. Specifically, he has achieved the total syntheses of several biologically active natural products including (+)-steenkrtotin A, enmein-type natural products, halichondrin family natural products (halichondrin B and norhalichondrin B), and the anticancer drug eribulin. He also participated in the total synthesis and medicinal chemistry studies of tubulysin analogues as potential payloads for anticancer antibody–drug conjugates in an academic– industrial collaboration.

Previous works by Dr. Saiyong Pan:

1. Nicolaou, K. C.^*; Pan, S.; Shelke, Y.; Rigol, S.; Bao, R.; Das, D.; Ye, Q. A Unified Strategy for the Total Syntheses of Eribulin and a Macrolactam Analogue of Halichondrin B. Proc. Natl. Acad. Sci. U.S.A.2022, 119, e2208938119.

2. Nicolaou, K. C.^*; Pan, S.; Shelke, Y.; Ye, Q.; Das, D.; Rigol, S., A Highly Convergent Total Synthesis of Norhalichondrin B. J. Am. Chem. Soc.2021, 143, 20970–20979.

3. Nicolaou, K. C.^*; Pan, S.; Shelke, Y.; Das, D.; Ye, Q.; Lu, Y.; Sau, S.; Bao, R.; Rigol, S., A Reverse Approach to the Total Synthesis of Halichondrin B. J. Am. Chem. Soc. 2021, 143, 9267–9276.

4. Nicolaou, K. C.^*; Pan, S.; Pulukuri, K. K.; Ye, Q.; Rigol, S.; Erande, R. D.; Vourloumis, D.; Nocek, B. P.; Munneke, S.; Lyssikatos, J.; Valdiosera, A.; Gu, C.; Lin, B.; Sarvaiaya, H.; Trinidad, J.; Sandoval, J.; Lee, C.; Hammond, M.; Aujay, M.; Taylor, N.; Pysz, M.; Purcell, J. W.; Gavrilyuk, J., Design, Synthesis, and Biological Evaluation of Tubulysin Analogues, Linker-Drugs, and Antibody–Drug Conjugates, Insights into Structure–Activity Relationships, and Tubulysin–Tubulin Binding Derived from X-ray Crystallographic Analysis. J. Org. Chem. 2021,86, 3377–3421. (Pan, S.; Pulukuri, K. K. and Ye, Q contribute equally)

5. Pan, S.; Chen, S.; Dong, G^*., Divergent Asymmetric Syntheses of Enmein-type Natural Products: (–)-Enmein, (–)-Isodocarpin, and (–)-Sculponin R. Angew. Chem. Int. Ed.2018, 57, 6333–6336.

6. Pan, S.; Gao, B.; Hu, J.; Xuan, J.; Xie, H.; Ding, H.^*, Enantioselective Total Synthesis of (+)-Steenkrotin A and Determination of Its Absolute Configuration. Chem. Eur. J.2016, 22, 959–970. (Pan, S. and Gao, B. contribute equally)

7. Pan, S.; Xuan, J.; Gao, B..; Zhu, A.; Ding, H.^*, Total Synthesis of Diterpenoid Steenkrotin A. Angew. Chem. Int. Ed. 2015, 54, 6905–6908. (Pan, S. and Xuan, J. contribute equally)

8. Xuan, J.; Pan, S.; Zhang, Y.; Ye, B.; Ding, H.^*, Construction of the Tricyclic Core of Steenkrotin-type Diterpenoids via Intramolecular [3+2] Cycloaddition. Org. Biomol. Chem. 2015, 13, 1643–1646. (Xuan, J. and Pan, S. contribute equally)

9. Pan, S.; Zheng, L.; Nie, R.; Xia, S.; Chen, P.; Hou, Z.^*, Transesterification of Glycerol with Dimethyl Carbonate to Glycerol Carbonate over Na-Based Zeolites. Chin. J. Catal. 2012, 33, 1772–1777.

10. Nie, R.; Lei, H.; Pan, S.; Wang, L.; Fei, J.; Hou, Z.^*, Core-shell Structured CuO-ZnO@H-ZSM-5 Catalysts for CO Hydrogenation to Dimethyl Ether. Fuel 2012, 96, 419–425.

Lab Tour: