| Compounds containing purine skeletons are widely used in the treatment of tumors,thrombosis,viral infections and other diseases.Among them,6-alkyl purine derivatives are widely concerned because of their unique cytotoxicity,anti-cancer activity and cell suppression activities.Therefore,it is important to develop an efficient strategy to construct the alkyl module of the 6-purines.Based on the characteristics of free radical reaction to construct C-C,this thesis designed and realized two new alkylation of 6-purines strategy with 1,4-dihydropyridine（1,4-DHPs）and olefins as alkyl radical precursors.1.Using 1,4-DHPs as the alkyl radical precursor to achieve the C-H alkylation of6-purineIn this paper,ammonium persulfate induced the cracking of the 4-position C-C of1,4-DHPs to generate alkyl radicals,which were further coupled with purine substrates.The metal-free catalytic conversion of the 6-position C-H of the purine to the C-C was successfully achieved and obtained 38 6-alkyl purine derivatives.This method overcomes the by-product of acylation caused by the direct use of aldehyde as an alkyl precursor in the traditional method.At the same time,the reaction shows a very high regioselectivity.Many functional groups such as esteryl,ketocarbonyl,cyanoyl,hydroxyl,carboxyl,terminal alkyne,C=C,and carbon-halogen bond show good compatibility.Both the primary and secondary alkyl groups can be successfully introduced into the 6-position with a superior yield,the highest yield is 96%.Further amplification and derivatization experiments show that this method has good application prospects.Finally,the possible reaction mechanism of this reaction is proposed based on the results of control experiments and previous studies.2.Using olefin as the alkyl radical precursor to realize the alkylation of C-H at the6-purineIn this paper,alkyl radicals are generated by olefins under the combined action of sodium borohydride and ferric nitrate nonahydrate through single electron transfer,and further reacted with purine derivatives to obtain key intermediates.Finally,aromatization achieved of the 6-purine under the action of O2 and successfully synthesized 32 6-alkyl purine derivatives.At the same time,experimental investigations have shown that purine substrates containing amides,C≡C,and ketone carbonyl,which are sensitive to sodium borohydride in the presence of Lewis acids,can obtain the target compound in moderate to excellent yields,and contain cyanide Purine substrates with functional groups such as alcohol and alcohol can achieve6-position alkylation with excellent yield.In terms of olefins,most of the cyclic and chain olefins and olefin substrates containing multiple functional groups can achieve6-position alkylation in good yield,and electron-deficient olefins are not conducive to this reaction.Finally,through deuteration tracing and other control experiments and related research,the possible mechanisms of the reaction is proposed.The structures of the above compounds were confirmed by NMR,IR and HRMS. |
