When the spectrum was accumulated on the next day or later the signals for the hydroxyl protons disappeared Ku-0059436 in vitro because of the hydrogen deuterium exchange. Compound (11) was also isolated from Azadirachta
indica (Siddiqui et al., 2003) and Esenbeckia berlandieri ssp. Acapulcensis (Cano et al., 2006). Substrate (4) used in the above reaction was present in hops in low quantity (Faltermeier et al., 2006; Oosterveld et al., 2002). For testing whether the demethylation depends on chain length of alkyl group, pentyl derivative of isoxanthohumol (6) was synthesized. Demethylation of 7-O-pentylisoxanthohumol (6) to product (12) occurred with high yield of 84.8% (Table 2, Entry 7). Cleavage of allyl ethers of alcohols and phenols was observed using
lewis acids such as the CeCl3–NaI system (Bartoli et al., 2001; Thomas et al., 1999). Compound (8) was synthesized to check whether its demethylation was affected by deallylation. learn more There was a possibility that MgI2, composed with magnesium (typical Lewis acid) and iodine (strong nucleophile) could be similar in action to CeCl3–NaI system. We did not observe the allyl–aryl ether cleavage and the desired product (13) were obtained with good 78.9% yield (Table 2, Entry 7). As in the case of alkyl ethers of isoxanthohumol, for testing whether the yield of demethylation depends on chain length of acyl group, diacetyl and dipalmitoyl derivatives of isoxanthohumol (9 and 10) were synthesized. These compounds, as representatives of esters, commonly applied as prodrugs, underwent demethylation with magnesium iodide etherate (Table 2, Entries 9 and 10). The products, isometheptene 8-prenylnaringenins (14 and 15) were obtained with 88.4 and 74.6% yield, respectively. Thus, introduction of alkyl, allyl or acyl group into isoxanthohumol moiety did not significantly influence the demethylation reaction and all the synthesized compounds were
stable during the course of reactions. Nevertheless, during the optimization of the isoxanthohumol demethylation (Anioł et al., 2008) to 8-prenylnaringenin the instability of reagents was observed, which could be associated with the known low stability of flavonoids. Investigations conducted by a group of Wilhelm and Wessjohann (2006) showed that demethylation of such compounds as isoxanthohumol was very difficult to carry out. Among the 17 demethylating agents only Sc(OTf)3/KI system worked with high yield. Our previous investigations demonstrated that this system could be replaced with MgI2 × 2Et2O to obtain 8-prenylnaringenin with 93% of yield. Now, we showed that this cheap, non toxic, easy to prepare and use agent could be applied in demethylation of acyl, alkyl, and allyl derivatives of isoxanthohumol. Antiproliferative activity, in vitro The synthesized compounds were examined for their antiproliferative activity in vitro against the human cell lines of breast cancer (MCF-7), colon adenocarcinoma (HT-29), and leukemia (CCRF/CEM).