A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling

TY - JOUR

T1 - A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling

AU - Beckmann, Henning S G

AU - Nie, Feilin

AU - Hagerman, Caroline E

AU - Johansson, Karl Henrik

AU - Tan, Yaw Sing

AU - Wilcke, David

AU - Spring, David R

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

U2 - 10.1038/nchem.1729

DO - 10.1038/nchem.1729

M3 - Journal article

C2 - 24056343

SN - 1755-4330

VL - 5

SP - 861

EP - 867

JO - Nature Chemistry

JF - Nature Chemistry

IS - 10

ER -