Performing the synthesis of a complex molecule on sequentially linked columns: toward the development of a "synthesis machine"

Abstract

[reaction: see text] We describe the diastereoselective synthesis of a pharmaceutically active drug candidate via a column-based system. This methodology is complementary to classical solid-phase synthesis; individual columns are packed with resin-bound reagents and then linked in sequence and/or in parallel. In contrast to the traditional solid-phase approach, substrates are introduced in the mobile phase where they build up chemical complexity by percolating through the linked columns, ultimately eluting as the desired product.