Title: Solid-Phase Synthesis of Heterocyclic Aromates: Applicability towards Combinatorial Chemistry, a Review
VOLUME: 6 ISSUE: 1
Author(s):E. Gelens, W. J. Koot, W. M.P.B. Menge, H. C.J. Ottenheijm and H. Timmerman
Affiliation:Leiden / Amsterdam Center for Drug Research (LACDR), Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
Keywords:solid-phase synthesis, heterocyclic aromates, combinatorial chemistry, heteroaromatic synthesis, traceless linkers
Abstract: Because of their biological activity, stability in vivo, the rigid spatial positioning of their substituents, and their synthetic challenges, heterocyclic aromates continue to be of interest to both academic and industrial medicinal chemists. Currently, many drug-like heterocyclic aromates are prepared via solidphase organic chemistry methods. This review examines the applicability of those methods towards combinatorial chemistry with respect to the basic demands of such an approach: 1) synthesis, work-up and subsequent purification should be easily automated enabling the efficient simultaneous synthesis of large numbers of highly pure compounds in a minimum amount of time, 2) large diversity among the ligands to be synthesized, 3) high conversion rates of the individual reaction steps, and 4) the use of commercially available starting materials. Although many methods have been developed for the synthesis of heterocyclic aromates, very few of the available methods enable the synthesis of highly diverse heteroaromatic libraries.
