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

摘要

Curcumin is a dietary diphenol with antioxidant, antinflammatory, and antitumor activity. We describe facile procedures for the synthesis of [~14C_2]curcumin (4 mCi/mmol), [d_6]curcumin, [d_3]curcumin, [~13C_5]curcumin, and [d_6]bicyclopentadione, the major oxidative metabolite of curcumin. We also describe synthesis of the labeled building blocks [~14C]vanillin, [d_3]vanillin, and [~13C_5]acetylacetone. The overall molar yields of the labeled products were 52 ([~14C]) and 47% ([d_3]) for vanillin and 25 ([~14C_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.