| Chapter 1 is divided into five parts, each roughly corresponding to the synthesis of library of small molecules utilizing click chemistry. Part 1 details the synthesis of a 275-member library utilizing nucleophilic opening of activated aziridines with amines. Additionally, certain aspects of the automation methodology exploited in the synthesis, including numbering schemes and process flow diagrams, are detailed. Part 2 describes several steps of manual synthesis following by a single automated step to produce a small molecule library. Part 3 extends the methodology described in part 1, detailing the synthesis of 315-member library via multistep automated synthesis using click-like reactions. Part 4 extends click chemistry methods to cyclic sulfamidates as capping reagents, a novel use for this type of electrophiles. Finally, part 5 details the synthesis of polyols from dienes using slightly-modified Upjohn conditions, with isolation only by filtration of solid precipitates.; Chapter 2 is also segmented into five parts. This chapter describes efforts direct toward integrating several components of a modular-design automation laboratory, specifically a Bohdan weighing and dissolution station, a Gilson 215 liquid handler, a computer workstation acting as a barcode-reading station, and several databases including an entry-level database system and a more powerful SQL-based database engine. These components were integrated using web applications based upon CGI (common gateway interface) applications written in the computer language Perl. Additionally, a single database application was written which can directly control a Gilson 215 liquid handler for the purpose of “cherry-picking” for creation of custom compound collections from existing libraries. |
