Natural product-like combinatorial libraries based on privileged structures. 3. The "libraries from libraries" principle for diversity enhancement ofbenzopyran libraries

As described in the preceding two papers, our interest in the construction of natural and natural product-like libraries for chemical biology studies led to the development of a new solid-phase cycloloading strategy for the c onstruction of substituted benzopyrans. Herein, we report a parallel soluti on-phase method that facilitates the enhancement of both the size and diver sity of these non-oligomeric benzopyran libraries using the "libraries from libraries" principle. We examine the rationale behind the use of this tand em strategy to construct discrete small molecule libraries, and describe th e development of a polymer-assisted solution-phase (PASP) methodology neces sary to effect the required transformations. Once developed, this chemistry is applied to two demonstration libraries.