Regioselective arylsulfenylation and arylselenenylation at 5-position of uracils mediated by bis(trifluoroacetoxy)iodobenzene

Abstract

Regioselective phenylsulfenylation and phenylselenenylation of uracil nucleosides at C-5 has been successfully achieved by the reaction with diphenyldisulfide or diphenyldiselenide in the presence of [bis(trifluoroacetoxy)iodo]benzene in acetonitrile with good yields. The characteristic points of these reactions are (ⅰ) easily available diphenyldisulfide (diphenyldiselenide) can be used as an electrophile, (ⅱ) the reaction can be performed under the mild conditions, (ⅲ) the hypervalent iodine reagent is simpler and safer than the general metallic reagents, (ⅳ) the reaction shows high regioselectivity. The present methods could be applicable to the synthesis of various types of 5-substituted uracil nucleosides. As the studies on PLC inhibitors and PI-turnover inhibitors from the $CH_2Cl_2$ layer of Erythrina senegalensis using NIH3T3γ1 cells, we isolated the eight flavonoids named as 8-prenylluteone, auriculatin, erysenegalensein N, erysenegalensein D, erysenegalensein O, derrone, alpinumisoflavone and 6, 8-diprenylgenistein. 8-Prenylluteone and auriculatin with isoprenyl group have showed the same inhibition effect on the PI-turnover in the NIH3T3γ1 cells and the same enzymatic activity of PLC with $IC_{50}$ of $20μM$, while the common flavonoids showed very weak inhibitory activity and had more than $IC_{50}$ of $250μM$. It is suggested that the isoprenyl group is related to the inhibitory activity against PLCγ1 and PI-turnover in the NIH3T3γ1 cells. In addition, these flavonoids were examined for cytotoxicity against several human tumor cell lines, i.e., PC-3 (prostate), NCI-H226 (lung), CRL1579 (melanoma) in vitro. The two compounds showed a moderate cytotoxicity ($IC_{50}$ of $9.0-20μM$). But auriculatin showed more potent inhibition than 8-prenylluteone on PC-3 and CRL1579 cell lines.