Natural product derivatization with β-lactones, β-lactams and epoxides toward 'infinite' binders. Issue 24 (14th June 2019)

• Record Type: Journal Article
• Authors: Jouanneau, Morgan; Vellalath, Sreekumar; Kang, Guowei; Romo, Daniel
• Is Part Of: Tetrahedron. Volume 75:Issue 24(2019)
• Page Start: 3348
• Page End: 3354
• Publication Date: 2019-06-14
• Subjects: [2+2] Cycloaddition -- Proteomics tools -- Isocyanates -- Natural product tagging -- Michael aldol-lactonization; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2019.04.068
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: β-Lactones, β-lactams and epoxides are privileged structural motifs found in both therapeutics and natural products. Herein we report several strategies for annulation of these motifs onto natural products that are not known to covalently modify their cellular targets. These strategies can facilitate identification of previously unidentified cellular targets or identify novel cellular targets of these natural products. The reported strategies include telescoped synthesis of β-lactones from allylic alcohols, nucleophile-catalyzed Michael aldol-β-lactonizations, and [2 + 2] β-lactam annulations with complex, commercially available alkene-containing natural products as substrates. A novel method for the tagging of phenolic natural products with epoxides is also reported. Graphical abstract: Image 1