A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling.
A prerequisite for successful screening campaigns in drug discovery or chemical genetics is the availability of structurally and thus functionally diverse compound libraries. Diversity-oriented synthesis (DOS) provides strategies for the generation of such libraries, of which the build/couple/pair (B/C/P) algorithm is the most frequently used. We have developed an advanced B/C/P strategy that incorporates multidimensional coupling. In this approach, structural diversity is not only defined by the nature of the building blocks employed, but also by the linking motif installed during the coupling reaction. We applied this step-efficient approach in a DOS of a library that consisted of 73 macrocyclic compounds based around 59 discrete scaffolds. The macrocycles prepared cover a broad range of different molecular shapes, as illustrated by principal moment-of-inertia analysis. This demonstrates the capability of the advanced B/C/P strategy using multidimensional coupling for the preparation of structurally diverse compound collections.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Henning S G
HS
Beckmann
Feilin
F
Nie
Caroline E
CE
Hagerman
Henrik
H
Johansson
Yaw Sing
YS
Tan
David
D
Wilcke
David R
DR
Spring
D055808:Drug Discovery; D047028:Macrocyclic Compounds / Q000737:chemistry*; D015394:Molecular Structure; D054852:Small Molecule Libraries
D047028:Macrocyclic Compounds; D054852:Small Molecule Libraries