Synthesis of Vitamin E-Carnosine (VECAR): New Antioxidant Molecule with Potential Application in Atherosclerosis

Abstract

Natural antioxidants such as carnosine and α-tocopherol (vitamin E) provide protection against several oxidative stress–related diseases such as atherosclerosis and Alzheimer's. The synthetic combination of α-tocopherol and carnosine can take advantage of the cellular transport mechanism of α-tocopherol by α-tocopherol transfer protein (α-TTP) to colocate α-tocopherol and carnosine at the interface between a lipophilic and a hydrophilic domain and protect both from oxidation. Successful synthesis of a novel heterodimer of α-tocopherol (vitamin E) and carnosine, VECAR was carried out in a total of nine steps. The VECAR design uses a 13-carbon phytyl-chain mimic to link carnosine to Trolox at the C2 carbon position. This design feature is anticipated to maintain binding to α-TTP, while maintaining the antioxidant activity of the two heterodimer components. Our results confirmed that there was no loss in antioxidant activity in VECAR using an in-vitro DPPH assay, versus α-tocopherol and Trolox.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental.

GRAPHICAL ABSTRACT

Keywords:

• Alzheimer's
• antioxidant
• atherosclerosis
• carnosine
• α-tocopherol
• Trolox

ACKNOWLEDGMENTS

We thank NSF (CBET-0854105) and ACS Petroleum Fund for funding this work.