Advanced Organic Chemistry Laboratory: A Multistep Synthesis toward the Preparation of a Small Library of Antituberculosis Compounds

A drug discovery project has been successfully implemented in an advanced undergraduate organic chemistry laboratory. In the laboratory, a five-step synthetic sequence is used to prepare five analogues of 13-phenyl-1-tridecanol. These compounds are key precursors in the synthesis of 2-oxo-14phenyltetradecanes. This class of compounds, isolated from the plant Piper sanctum, exhibit bioactivity against Mycobacterium tuberculosis, the bacterium responsible for causing tuberculosis. The laboratory was designed to provide students with an authentic research experience. The sequence incorporates many common organic transformations: S(N)2 bromination of a primary alcohol, silyl ether protection/deprotection, ylide formation and subsequent Wittig reaction, and hydrogenation. The reactions all provide good yield and high purity of the desired products. Purification, using column chromatography, is only required after one step in the sequence. The laboratory teaches students the techniques and equipment required to perform organic synthesis, what to write in a laboratory notebook, and how to present this experimental data in a peer-reviewed journal.