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
Thomas E .Storra, Sarah J. Cully, Michael J. Rawling, William Lewis, Daniel Hamza, Geraint Jones, Robert A. Stockman
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.
Ref: Bioorgan. Med. Chem., 23, (11), 2621 – 2628