肌苷衍生物的碱基核糖化研究

目的研究N1-核糖肌苷衍生物的合成反应。方法用丙叉保护肌苷2′,3′-OH,单甲氧基三苯甲基保护5′-OH,在碳酸钾、18-冠醚-6作用下与2,3,5-O-三苄基-1-溴代核糖反应。结果反应得到N1-核糖肌苷衍生物。结论用酰基做保护基易发生酰基重排反应,改用丙叉保护肌苷2′,3′-OH,再用单甲氧基三苯甲基保护5′-OH与2,3,5-O-三苄基-1-溴代核糖在碳酸钾18-冠醚-6作用下得到目的物N1-(2,3,5-O-三苄基-D-核糖)-2′,3′-O-异亚丙基-5′-O-单甲氧基三苯甲基肌苷。

An Investigation on the Synthesis of N1-ribosylinosine

Objective Cyclic adenosine diphosphoribose(cyclic ADP-ribose or cADPR), a recently discovered metabolite of nicotinamide adenine dinucleotide(NAD), is a potent calcium releasing agent postulated to be a new second messenger. In this paper, we wish to report an investigation of the reaction on the synthesis of N¹-ribosylinosine as an important intermediate of cyclic inosine diphosphoribose(cIDPR) as an analog of cADPR. Methods To find a straightforward method for the synthesis of N¹-ribosylation of inosine derivatives, phase transfer catalysis(PTC) reaction was applied. Benzoylated inosine reacted with benzoylated 1-ribosyl bromide in the presence of K₂CO₃ and 18-C-6 ether gave N¹-benzoylinosine derivative by benzoyl rearrangement. Reaction of acylated inosine with acylated 1-ribosyl bromide was carried out under similar condition resulted in the formation of the corresponding N¹-acetylinosine derivative. NMR and IR spectral analysis of the product supported the conclusion. The H-2, H-8 proton signal, and C-4, C-5, C-6 carbon signal showed distinct starting material correlation peak. H-2, H-8 proton signals and C-4, C-6 carbon signals appear at higher and C-5 carbon signal appear at lower than starting material correlation peak. We treated 2', 3'-o-isopropylidene-5'-o-p-anisyldiphenylmethylinosine and 2', 3'-o-benzoyl-5'-o-p-anisyldiphenylmethylribosyl bromide to give the corresponding N¹-benzoylated species as the main product and a trace amount N¹-ribosylinosine. To avoid acyl transformation, 2', 3'-o-isopropylidene-5'-o-p-anisyldiphenylmethylinosine was chose as reacting substance which reacted with 2,3,5-tri-o-benzylribosyl bromide under similar condition. Results As expected, N¹-ribosylinosine derivative was obtained. In the reaction a 1∶ 4 N¹-linked mixture of α and β-glucoside is observed. Spectral data supporting this conclusion included the mass spectrum and the ¹HNMR spectrum. Conclusion Reaction of acylated inosine with acylated 1-ribosyl bromide was carried out in the presence of K₂CO₃ and 18-C-6 ether resulted in the formation of the corresponding N¹-acetylinosine derivative. To avoid acyl transformation, 2', 3'-o-isopropylidene-5'-o-p-anisyldiphenylmethylinosine reacted with 2,3,5-tri-o-benzylribosyl bromide under similar condition to produce N¹-ribosylinosine.