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. Issue 11 (1st June 2015)

• Record Type: Journal Article
• Authors: Storr, Thomas E.; Cully, Sarah J.; Rawling, Michael J.; Lewis, William; Hamza, Daniel; Jones, Geraint; Stockman, Robert A.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 11(2015)
• Page Start: 2621
• Page End: 2628
• Publication Date: 2015-06-01
• Subjects: sp3-rich -- Natural product-like -- Scaffold -- Cycloaddition -- Two-directional -- Macrocycle -- Library -- Tandem; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2014.12.050
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.