CHAPTER 11. Vitamin E Inspired Synthetic Antioxidants

Abstract

The search for novel antioxidants inspired by the structure of vitamin E was made possible by rationalization of the physical–chemical properties at the basis of vitamin E bioactivity and has contributed significantly to such rationalization. Hundreds of novel compounds have been synthesized and tested, a representative selection of which (51 molecules) is illustrated and discussed in this chapter, highlighting the structure–activity relationships behind their antioxidant activity. Among them, BO-653, thiatocopherol and related compounds, selenotocopherol and related compounds, tellurophenols, N-tocopherol and related compounds, and Mito-Vitamin E are given special attention. The discussion focuses on the absolute rate constant for trapping peroxyl radicals in solution. When available, the performance in biomimetic models, like the protection of low density lipoproteins, along with the results of in vivo testing for pharmaceutical applications is also addressed. Some of the synthetic analogues largely outperformed the most active natural α-tocopherol, both in model systems and in vivo. However, none of these compounds has yet reached medical practice or is currently approved as a pharmaceutical, which calls for further research.