Article

Natural product-like synthetic libraries.

Institute of Chemical and Engineering Sciences, Organic Chemistry, 11 Biopolis Way, Helios, Singapore 138667, Singapore.
Current opinion in chemical biology (Impact Factor: 8.3). 06/2011; 15(4):516-22. DOI: 10.1016/j.cbpa.2011.05.022
Source: PubMed

ABSTRACT There is a paucity of chemical matter suitably poised for effective drug development. Improving the quality and efficiency of research early on in the drug discovery process has been a long standing objective for the drug industry and improvements to the accessibility and quality of compound screening decks might have a significant and positive impact. In the absence of specific molecular information that can be modeled and used predicatively we are far from identifying which small molecules are most relevant to emerging biological targets such as protein-protein interactions. Natural products have been historically successful as an entry point for drug discovery and recently screening libraries are being synthesized to emulate natural product like features.

1 Bookmark
 · 
134 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Catalytic, selective, and controlled oxidative functionalization of CH bonds using molecular oxygen as an oxidant remains highly desirable and equally challenging in the development of synthetic methodologies. Presented herein is a one-pot oxygenase cascade reaction wherein a copper(I)-catalyzed oxygenase reaction transforms the allylic methyl group in 3-methylidene oxindoles into an aldehyde, which then undergoes an aldol-oxa-Michael addition sequence with β-ketoesters to yield dihydrofuran-bearing oxindoles.
    Angewandte Chemie International Edition in English 05/2014; · 13.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Screening of small-molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries because of their structural complexity and sp(3)-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin and Amaryllidaceae). In each case, scaffolds were based on structures of the naturally occurring compounds or a close derivative. Scaffold preparation was pursued following the development of appropriate enabling chemical methods. Diversification provided 686 new compounds suitable for screening. The libraries thus prepared had structural characteristics, including sp(3) content, comparable to a basis set of representative natural products and were highly rule-of-five compliant.
    Nature Chemistry 02/2014; 6(2):133-40. · 21.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Highly functionalized quinolines and pyridines could be synthesized by BF3 ⋅OEt2 -mediated reactions of vinyl azides with N-aryl and N-alkenyl aldimines, respectively. The reaction mechanism could be characterized as formal [4+2]-annulation, including unprecedented enamine-type nucleophilic attack of vinyl azides to aldimines and subsequent nucleophilic cyclization onto the resulting iminodiazonium ion moieties.
    Chemistry - An Asian Journal 06/2014; · 4.57 Impact Factor