Natural product-like combinatorial libraries based on privileged structures. 2. Construction of a 10 000-membered benzopyran library by directed split-and-pool chemistry using NanoKans and optical encoding

Having developed a reliable and versatile solid-phase strategy for the spli t-and-pool synthesis of naturally occurring and designed derivatives of the benzopyran template (see preceding paper), we now report the construction of a 10 000-membered natural product-like compound library for chemical bio logy studies. Concomitantly, we report an early application of the IRORI Na noKan optical encoding system for the high throughput nonchemical tagging a nd sorting of library members during split-and-pool synthesis. The overall synthetic strategy for library construction is discussed and the individual reaction pathways are examined in the context of specific library members, illustrating reaction conditions as well as yields and purities, The issue s of building block selection and quality control of library members are al so addressed and, finally, potential applications of the library to chemica l biology are discussed.