A highly α-regioselective prenylation of imines has been successfully developed. The efficiency of this approach is confirmed by a wide range of imines including N- and C-aryl aldimines, N-alkyl aldimines, C-alkyl aldimines, and N- and C-aryl ketimines. The approach uses prenyl bromide as the prenyl source and inexpensive and convenient zinc as the mediator as well as environmentally benign 1,3-dimethyl-2-imidazolidinone (DMI) as the solvent.

A series of conjugates of 5-Fluorouracil (5-FU) and emodin were synthesized by coupling trimethyl emodin with N1, N3 dialkylated 5-FU. The 5-FU moiety contained various substituents at the N3-position were linked to the 2-position of trimethyl emodin via a methylene linkage. Their cytotoxicity against three cancer cell lines and one noncancerous cell were studied. The results revealed that some of conjugates exhibited better or comparable in vitro antitumor activity to 5-FU and emodin and low toxicity in the normal cell. The structure–activity relationship study showed N3-aromatic substituent was important for their cytotoxic activity.A series of conjugates of 5-FU and emodin were synthesized and evaluated for their antitumor activity. The structure–activity relationship showed N3-aromatic substituent is important for their cytotoxic activity. Highlights► A series of conjugates of 5-Fluorouracil and emodin were synthesized. ► Their in vitro antitumor activity was tested. ► The SAR showed N3-aromatic substituent was important for their cytotoxic activity.

A simple, efficient, and general α-prenylation approach for the synthesis of a variety of α-prenylated alcohols has been successfully developed. A wide range of α-prenylated alcohol derivatives could be obtained in good yields by highly α-regioselective zinc-mediated prenylation of various aldehydes and ketones with prenyl bromide at 120 °C in HMPA. By simply altering the reaciton solvent and temperature, the method allows the achievement of a highly notable opposite regiocontrol, providing the expected regiochemical product. The method provides a convenient route for the direct α-prenylation of carbonyl compounds in a highly α-regioselective manner using a cheap and convenient mediator. Two possible pathways are proposed to account for the formation of these synthetically difficult-to-obtain molecules.

Hydroxymethylation of 6,8-O-dimethyl emodin was easily achieved in good yields by the modified Marschalk reaction. The influence of the amount of solvent, base and formaldehyde toward the hydroxymethylation was discussed. The results showed that a relatively dilute reaction solution facilitated the generation of the desired 2-hydromethyl product, while the thick reaction solution benefited the generation of the methylated quinizarins.