small molecule library synthesis using segmented flow使用分段流合成小分子库.pdfVIP

Molecules 2011, 16, 9161-9177; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Small Molecule Library Synthesis Using Segmented Flow Christina M. Thompson 1,*, Jennifer L. Poole 2, Jeffrey L. Cross 1, Irini Akritopoulou-Zanze 1 and Stevan W. Djuric 1 1 Medinical Chemistry Technologies, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA 2 Department of Chemistry at KU, 1251 Wescoe hall Drive, 2010 Marlott Hall, Lawrence, KA 66045, USA * Author to whom correspondence should be addressed; E-Mail: Christina.m.thompson@. Received: 13 September 2011; in revised form: 18 October 2011 / Accepted: 21 October 2011 / Published: 2 November 2011 Abstract: Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 µL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave