Small Molecule Library Synthesis Using Segmented Flow 英文参考文献.docVIP

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 synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently. Keywords: segmented flow; library synthesis 1. Introduction Flow chemistry reactors have received increased attention over the last decade as flexible platforms for organic synthesis. Their modular and simple designs have been adapt