Ternary resin-bound Dynamic Combinatorial Chemistry

Abstract

The ability to carry out simultaneous orthogonal exchange chemistries has opened new opportunities for increasing the numerical and structural diversity accessible to Dynamic Combinatorial Chemistry. We present proof-of-concept experiments demonstrating this concept is transferrable to resin-bound DCC, facilitating the generation and analysis of libraries with greater structural diversity.

Fig. 1

(a) Resin-bound dynamic combinatorial library and (b) Ternary resin-bound dynamic combinatorial library generation

Fig. 2

Library members. For solution phase experiments, R = (CH₂)₃NH₂; for resin-bound experiments, R = (CH₂)₅CONH₂

Fig. 3

Solution phase library constructed from A1, A2, B1, B2 and thiopropanol (green trace); B1, B2, C1, C2 and aniline (red trace); A1, A2, B1, B2, C1, C2, thiopropanol and aniline (blue trace) after 3 days of equilibration in ammonium acetate buffer (pH 7.4).

Fig. 4

Resin bound library constructed from A1 and C1 in solution and resin bound B1, after 6 days of equilibration in the presence of aniline at pH 7.4

Fig. 5

Resin bound library constructed from A1, A2, C1, C2 in solution and resin bound B1 and B2, after 1 week of equilibration in the presence of aniline at pH 7.4.