Rapid Synthesis of a Natural Product-Inspired Uridine Containing Library

Abstract

The preparation of natural product-inspired nucleoside analogs using solution-phase parallel synthesis is described.The key intermediates containing alkyne and N-protected amino moieties were developed to allow for further skeleton and substituent diversity using click chemistry and urea or amide bond formation. Rapid purification was accomplished using solidphase extraction. The obtained library comprised 80 molecules incorporating two diversity positions and one chiral center, each of which was efficiently prepared in good purity and acceptable overall yield. A bacterial morphology study was also performed.

Synthesis of Nitrone‐derived Pyrrolidine Scaffolds and Their Combinatorial Libraries to Develop Selective α‐l‐Rhamnosidase Inhibitors

“…Recently monocyclic or bicyclic iminosugar-based scaffolds from the corresponding chiral cyclic nitrones have been developed and reported in our previous studies, [21,22] and we have used them to build diverse libraries with three diversity elements (core, configuration, and substituent) based on Natural product-inspired combinatorial chemistry (NPICC). [23,24] For example, we have successfully applied this strategy to discover novel protein stabilizers of lysosomal α-galactosidase for the potential treatment of Fabry disease [25,26] and inhibitors against human Golgi α-mannosidase II as potential cancer therapy. [27] To the best of our knowledge, however, the use of this approach to prepare diverse scaffolds and molecular libraries to increase molecular complexity in chemical space for developing α-l-Rha-ase inhibitors has yet to be explored.…”