NMR Methods for the Assignment of Absolute Stereochemistry of Bioactive Compounds

Abstract

The absolute stereochemistry of a compound is essential to understand many of its chemical, biological, and pharmaceutical properties and therefore the development of easy-to-use methods for its determination in solution is of utmost interest for researchers involved in bioactive compounds. Among several techniques available, derivatization of the chiral compound with adequate chiral derivatizing agents (CDAs) followed by NMR analysis of the resulting derivatives is particularly appealing because the instrumentation is currently available practically in all laboratories, and just a small amount of sample, that can be recovered in many cases, and a short time are required to provide a reliable assignment. In this article, we present the essentials of this NMR procedure and the structure and uses of the most important CDAs. It also enumerates different classes of compounds whose absolute configuration can be assigned by this methodology, all illustrated with examples of its application. The potential of this NMR procedure is exemplified with a selection of bioactive natural products whose absolute configuration has been assigned by this methodology. Keywords: absolute configuration; NMR; arylalkoxyacetic acids; chiral derivatizing agents; bioactive compounds; complexation shifts; low-temperature NMR; barium complex; resin-bound CDA