title: Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp(3)-rich library.
abstract: The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp(3)-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 sp(3)-rich natural product-like library.
authors: School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: Thomas E
authors: TE
authors: Storr
authors: School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: Sarah J
authors: SJ
authors: Cully
authors: School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: Michael J
authors: MJ
authors: Rawling
authors: X-ray Crystallography Section, School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors: William
authors: W
authors: Lewis
authors: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
authors: Daniel
authors: D
authors: Hamza
authors: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, UK.
authors: Geraint
authors: G
authors: Jones
authors: School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: robert.stockman@nottingham.ac.uk.
authors: Robert A
authors: RA
authors: Stockman
mesh_terms: D000588:Amines / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D047028:Macrocyclic Compounds / Q000138:chemical synthesis*; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis*
chemical_list: D000588:Amines; D001688:Biological Products; D047028:Macrocyclic Compounds; D054852:Small Molecule Libraries
keywords: Cycloaddition; Library; Macrocycle; Natural product-like; Scaffold; Tandem; Two-directional; sp(3)-rich