Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library

Storr, Thomas E.; Cully, Sarah J.; Rawling, Michael J.; Lewis, William; Hamza, Daniel; Jones, Geraint; Stockman, Robert A.

Abstract

The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp3-rich tricyclic pyrazoline scaffold with two ethyl esters in a single step from a simple linear starting material. The successive hydrolysis and cyclisation (with Boc anhydride) of these 3-dimensional architectures, generates unprecedented 16-membered macrocyclic bisanhydrides (characterised by XRD). Selective amidations could then be achieved by ring opening with a primary amine followed by HATU-promoted amide coupling to yield an sp3-rich natural product-like library.

Citation

Storr, T. E., Cully, S. J., Rawling, M. J., Lewis, W., Hamza, D., Jones, G., & Stockman, R. A. (2015). Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library. Bioorganic and Medicinal Chemistry, 23(11), https://doi.org/10.1016/j.bmc.2014.12.050

• Journal Article Type: Article
• Acceptance Date: Dec 18, 2014
• Online Publication Date: Dec 29, 2014
• Publication Date: Jun 1, 2015
• Deposit Date: Sep 28, 2017
• Publicly Available Date: Sep 28, 2017
• Journal: Bioorganic and Medicinal Chemistry
• Print ISSN: 0968-0896
• Electronic ISSN: 1464-3391
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 11
• DOI: https://doi.org/10.1016/j.bmc.2014.12.050
• Keywords: sp3-rich; Natural product-like; Scaffold; Cycloaddition; ; Two-directional; Macrocycle; Library; Tandem
• Public URL: https://nottingham-repository.worktribe.com/output/750700
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0968089614009080
• Contract Date: Sep 28, 2017