Site-Specific Deuteration of Polyunsaturated Alkenes

• Published in: Journal of organic chemistry 2017-12, Vol.82 (24), p.13115-13120
• Main Authors: Smarun, A. V, Petković, M, Shchepinov, M. S, Vidović, D
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Deuterium; Deuterium Oxide - chemistry; Fatty Acids, Unsaturated - chemistry; Models, Molecular; Radiopharmaceuticals; Substrate Specificity
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b02169

Selective deuteration of drugs and biologically relevant molecules is becoming increasingly important in the pharmaceutical industry. Site-selective isotopic reinforcement of polyunsaturated fatty acids (PUFAs) at their bis-allylic sites has been identified as a unique approach in preventing oxidative damage in these molecules, which had been linked to neuronal and retinal diseases, atherosclerosis, and aging. Typical methods for preparation of site-selectively deuterated PUFAs require rather long, laborious, and expensive syntheses. In this report, we disclose a very efficient catalytic protocol for site-specific deuteration of PUFAs and analogous poly-alkenes under exceptional kinetic control. Deuterium oxide (D2O) has been identified not only as a deuterium source but also as a crucial component in the overall reaction mechanism responsible for averting the formation of thermodynamically favored side-products.