Synthesis of a Novel Tocopherol/Carotenoid Derivative

Abstract

The goal of this work is the synthesis of a tocopherol/carotenoid hybridderivative (1, figure II). The novel derivative is believed to exhibitsynergistic antioxidant effects between its chromanol and polyene consituents.The synthesis of 1 was completed up to and including theimmediate precursor 12.Commercially avaliable Trolox (7) was reduced by Red-Al® to 8(step a) in 95% yield. Chromanol aldehyde 9 was formed by Swernoxidation of 8 in 65% yield (step b). Wittig reaction between 9 andphosphonium salt 10 afforded 11 in 33% yield and varying cis : transratio (step c), and subsequent elongation produced 12 (14% yield, stepd). The Wittig reactions were performed with reflux and microwaveirradiation.Various attempts at protecting the phenolic group in intermediate8 by silylation or benzylation did only lead to formation of 8B.Oxidation of 8 by the Dess-Martin oxidation formed the unexpectedquinone-like derivative 27. Efforts to protect the phenolic group in intermediate9 by benzoylation and silylation only produced 9A, foundto be unsoluble in all common laboratory solvents.