Stereochemistry and Antioxidant Activity of 1,3‐Diol Derivatives of Diacetylcurcumin‐4H: A Joint NMR, X‐Ray, and Biological Approach

The stereochemistry of two new 1,3‐diol curcuminoid derivatives, ((3R*,5R*)‐3,5‐dihydroxyheptane‐1,7‐diyl) bis (2‐methoxy‐4,1‐phenylene) diacetate namely rac‐6, its acetylated derivative, (3R*,5R*)‐1,7‐bis(4‐acetoxy‐3‐methoxyphenyl) heptane‐3,5‐diyl diacetate (rac‐7) and the diastereomeric model compound 1,3‐bis(4‐methoxyphenyl)‐1,3‐propanediol (rac‐2) were investigated through their X‐ray crystal structures and nuclear magnetic resonance spectra. Achiral compounds diacetylcurcumin (4) and diacetylcurcumin‐4H (5), crystallized in the Sohncke space group P21 allowed its unambiguous stereochemical assignment. The unit cell of tetraacetylated compound rac‐7 consists of a co‐crystal of two conformers and constitute a rare case of conformational isomorphism composed by TTTTTT and TTTTGT conformers in a 1:1 stoichiometric proportions. The antioxidant activity of each pair of derivatives was investigated and a significant difference in activity was found for tetraacetylated pairs rac‐7/(3R,5 S)‐1,7‐bis(4‐acetoxy‐3‐methoxyphenyl) heptane‐3,5‐diyl diacetate (meso‐7) and cyclic sulfites (((4R*,6R*)‐2‐oxido‐1,3,2‐dioxathiane‐4,6‐diyl) bis (ethane‐2,1‐diyl)) bis (2‐methoxy‐4,1‐phenylene) diacetate (rac‐8)/(((4 S,6R)‐2‐oxido‐1,3,2‐dioxathiane‐4,6‐diyl) bis (ethane‐2,1‐diyl)) bis (2‐methoxy‐4,1‐phenylene) diacetate (meso‐8). The present study addresses the stereochemistry and biological activity of these types of compounds. A detailed spectroscopic study of 1,3‐diols of curcuminoids with broad biological activities is given. The crystal structures of a 1,3‐diol curcuminoid and its acetylated derivative are reported for the first time, the latter illustrating a rare example of conformational isomorphism.