FLUOROUS LINKER-FACILITATED SYNTHESIS OF BIOLOGICALLY INTERESTING MOLECULES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 332

10
FLUOROUS
LINKER-FACILITATED
SYNTHESIS OF BIOLOGICALLY
INTERESTING MOLECULES

CHAPTER

WEI ZHANG
Department of Chemistry, University of Massachusetts, Boston, Massachusetts, USA

10.1. INTRODUCTION

Phase tag-facilitated separation is an important technique in organic synthesis,
especially for parallel and high-throughput synthesis (HTS) of compound libraries;
the best-known example being the solid-phase synthesis of peptides. The solid-phase
technique has also been developed for HTS of small molecule libraries. Different
from peptide synthesis that repeatedly generates amide bonds, small molecule
synthesis involves a wide range of different kinds of reactions. It is worth noting,
however, that many reactions are not suitable for solid-phase reactions due to
unfavorable kinetics, usually observed in heterogeneous reactions, or due to extended
amount of time needed for method development.
Fluorous chemistry combines homogeneous solution-phase reactions and easy
phase tag separations to increase synthetic efficiency. This technology relies on the
lipo- and hydrophobic properties of fluorous tags for the selective separation of
attached molecules. Since it was first introduced by Horvath and Rabai in 1994 in the
context of fluorous biphasic catalysis [1], Curran, Zhang, Pohl, and many others have
made contributions to improve the efficiency of the synthesis of small molecules,
biomolecules, organocatalysis, biocatalysis, proteomics, microarray, microfluidics,
and nanomaterials [2-12]. Described in this chapter are the applications of “light
fluorous” linkers for the synthesis of natural product analogues and biologically
interesting molecules.