Facile synthesis of deuterated and [14C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Curcumin is a dietary diphenol with antioxidant, antinflammatory, and antitumor activity. We describe facile procedures for the synthesis of [C-14(2)]curcumin (4mCi/mmol), [d(6)]curcumin, [d(3)]curcumin, [C-13(5)]curcumin, and [d(6)]bicyclopentadione, the major oxidative metabolite of curcumin. We also describe synthesis of the labeled building blocks [C-14]vanillin, [d(3)]vanillin, and [C-13(5)]acetylacetone. The overall molar yields of the labeled products were 52 ([C-14]) and 47% ([d(3)]) for vanillin and 25 ([C-14(2)]) and 27% ([d(6)]) for curcumin. The compounds can be used as radiotracers in biotransformation studies and as isotopic standards for mass spectrometry-based quantification in pharmacokinetic analyses. Copyright (c) 2013 John Wiley & Sons, Ltd.