Unified synthesis of diverse building blocks for application in the discovery of bioactive small molecules. Issue 38 (20th September 2019)

• Record Type: Journal Article
• Authors: Rice, Scott; Cox, Daniel J.; Marsden, Stephen P.; Nelson, Adam
• Is Part Of: Tetrahedron. Volume 75:Issue 38(2019)
• Publication Date: 2019-09-20
• Subjects: Lead-oriented synthesis -- Molecular diversity -- Molecular scaffolds; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2019.130513
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The synthesis of large numbers of diverse molecular scaffolds with controlled molecular properties is a significant challenge in synthetic organic chemistry. A modular unified synthesis was developed, and was exploited in the synthesis of sixteen diverse three-dimensional scaffolds. The approach exploited two cyclisation precursors to be converted, using a toolkit of cyclisation reactions, into spirocyclic and fused-ring scaffolds. Remarkably, Pd-catalysed aminoarylation of substituted N -Boc-hex-5-enylamine cyclisation precursors to yield N- Boc piperidine-containing scaffolds was successful which was ascribed to a significant Thorpe−Ingold effect. Computational property analysis showed that the decorated scaffolds are shape-diverse, and enable diverse lead-like chemical space to be targeted. Graphical abstract: Image 1 Highlights: Unified synthesis of diverse building blocks. Pd-catalysed aminoarylation yields N- Boc piperidine-containing scaffolds. The decorated scaffolds are shape-diverse, and enable diverse lead-like chemical space to be targeted.