【摘要】：目的探索與優(yōu)化磷酰胺嗎啉代寡核苷酸(PMO)關(guān)鍵中間產(chǎn)物7'-羥基-N-三苯甲基嗎啉代核苷單體合成工藝路線和方法,使其合成更加高效與便捷,為以PMO為結(jié)構(gòu)基礎(chǔ)的反義寡核苷酸類藥物研究奠定基礎(chǔ)。方法以N4-苯甲�；�,鳥苷與5-甲基尿苷作為起始原料,經(jīng)過將核糖環(huán)結(jié)構(gòu)改造為嗎啉環(huán)并對關(guān)鍵化學(xué)基團保護等步驟合成7'-羥基-N-三苯甲基嗎啉代核苷單體。結(jié)果分別得到N4-苯甲�；�-7'-羥基-N-三苯甲基嗎啉代胞苷、N2-苯甲�；�-7'-羥基-N-三苯甲基嗎啉代鳥苷和7'-羥基-N-三苯甲基嗎啉代胸苷,并對三者合成的工藝方法進行了優(yōu)化,對所合成的中間體和目標(biāo)物進行了結(jié)構(gòu)確證。結(jié)論優(yōu)化后的7'-羥基-N-三苯甲基嗎啉代核苷單體合成工藝高效、便捷且適合放大制備。
[Abstract]:Objective to explore and optimize the synthetic route and method of 7-hydroxy-N-triphenylmethylmorpholine nucleoside (PMO), which is the key intermediate of phosphoramide morpholine oligodeoxynucleotide (PMO), so as to make it more efficient and convenient. It lays a foundation for the study of antisense oligodeoxynucleotides (ASODN) based on PMO. Methods using N4-benzoyl cytidine, guanosine and 5-methyluridine as starting materials, 7-hydroxy-N-triphenylmethylmorpholine nucleoside monomers were synthesized by modifying the ribosomal structure to morpholine ring and protecting the key chemical groups. Results N _ 4-benzoyl-7-hydroxy-N-triphenyl-methyl-morpholine cytidine, N _ 2-benzoyl-7-hydroxy-N-triphenylmethyl-guanosine and 7-hydroxy-N-triphenyl-N-triphenylmethylmorpholine cytidine, respectively, were obtained. The synthesis process was optimized and the structures of the intermediates and target compounds were confirmed. Conclusion the optimized synthesis process of 7-hydroxy-N-triphenylmethylmorpholine nucleoside monomer is efficient, convenient and suitable for amplification.
【作者單位】： 軍事醫(yī)學(xué)科學(xué)院微生物流行病研究所病原微生物生物安全國家重點實驗室;
【基金】：國家科技重大專項資助項目(2015ZX09102022)
【分類號】：R914.5

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