Complex Molecule Synthesis & Retrosynthesis


Complex molecules drive new reaction development and provide lead compounds for therapeutic translation. The identification of high-value retrosynthetic disconnections represent one of the most challenging tasks in accessing these complex scaffolds efficiently. In C-CAS, we aim to employ tools that inform chemists of optimal synthetic routes among the endless theoretical space of possible disconnects.


  • Bartholomew, G.L.; Kraus, S.L.; Karas, L.J.; Carpaneto, F.; Bennett, R.; Sigman, M.S.; Yeung, C.S.; Sarpong, R. “14N to 15N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing” ChemRxiv 2023 .10.26434/chemrxiv-2023-30dtw

  • Jie Xu, Samantha Grosslight, Kyle A. Mack, Sierra C. Nguyen, Kyle Clagg, Ngiap-Kie Lim, Jacob C. Timmerman, Jeff Shen, Nicholas A. White, Lauren E. Sirois, Chong Han, Haiming Zhang*, Matthew S. Sigman*, and Francis Gosselin. Atroposelective Negishi Coupling Optimization Guided by Multivariate Linear Regression Analysis: Asymmetric Synthesis of KRAS G12C Covalent Inhibitor GDC-6036. J. Am. Chem. Soc. 2022, 144, 45, 20955-20963.

  • Shen, Y., Borowski, J., Hardy, M., Sarpong, R. Doyle, A., Cernak, T. Automation and computer-assisted planning for chemical synthesis. Nat Rev Methods Primers, 2021, 23, 1.

  • Jordan, J. Dotson, Lucy van Dijk, Jacob C. Timmerman, Samantha Grosslight, Richard C. Walroth, Francis Gosselin, Kurt Püntener, Kyle A. Mack*, and Matthew S. Sigman*.  Data-Driven Multi-Objective Optimization Tactics for Catalytic Asymmetric Reactions using Bisphosphine Ligands. J. Am. Chem. Soc. 2022, Dec 27, 2022.

  • Jones, K.E.; Park, B.; Doering, N.A.; Baik, M.H.; Sarpong, R.  Rearrangements of the Chrysanthenol Core: Application to a Formal Synthesis of Xishacorene B. J. Am. Chem. Soc. 2021, 143, 20482–20490

  • Hardy, M.A.; Nan, B.; Wiest, O.; Sarpong, R.  Strategic elements in computer-aided retrosynthesis: A case study of the pupukeanane natural products Tetrahedron 2022, 103, 132584

  • Hardy, M.A.; Cooke, J.H.; Feng, Z.; Noda, K.; Kerschgens, I.; Massey, L.A.; Tantillo, D.J.; Sarpong, R. Unified Synthesis of 2-Isocyanoallopupukeanane and 9-Isocyanopupukeanane through a "Contra-biosynthetic" Rearrangement. Angew. Chem. Int. Ed. 2024, 63.