9-(6-脱氧-α- l - talofuranosyl)-6-甲基嘌呤和9-(6-脱氧-β- d - allofuranosyl)-6-甲基嘌呤核苷的合成

Q4 Chemistry
Abdalla E A Hassan, Reham A I Abou-Elkhair, Hend M Maaroof, John A Secrist
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引用次数: 1

摘要

6-甲基嘌呤(MeP)是一种细胞毒性腺嘌呤类似物,在系统给药时不表现出选择性,在涉及大肠杆菌嘌呤核苷磷酸化酶(PNP)的癌症基因治疗方法中非常有用。在大肠杆菌PNP/前药癌症基因治疗方法中,合成了9-(6-脱氧-β- d -异呋喃基)-6-甲基嘌呤[methyl(allo)- mepr, 18]和9-(6-脱氧-α- l -异呋喃基)-6-甲基嘌呤[methyl(talo)- mepr, 21]作为MeP的潜在前药。详细介绍了[甲基(allo)-MePR]和[甲基(talo)-MePR]的合成方法。以1,2:5,6-二- o -异丙基-α- d -葡萄糖葡萄糖(4)为原料,分别用9步和11步制备了糖基供体1,2-二- o -乙酰-3,5-二- o -苄基-α- d -己呋喃糖(12)和1- o -乙酰-3- o -苄基-2,5-二- o -苯甲酰-α-L-talofuranose(16)。后一种糖基供体与6-甲基嘌呤(3)的vorbr根偶联,然后是糖羟基的去保护,使标题化合物具有良好的总体产量。©2020 by John Wiley & Sons, Inc。基本方案1:制备6-甲基嘌呤基本方案2:制备d -己基呋喃糖衍生物(12)基本方案3:制备6-脱氧-α- l -talo呋喃糖基本方案4:制备甲基(allo)-MePR(18)基本方案5:制备甲基(talo)-MePR(21)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis of 9-(6-Deoxy-α-L-Talofuranosyl)-6-Methylpurine and 9-(6-Deoxy-β-D-Allofuranosyl)-6-Methylpurine Nucleosides.

6-Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9-(6-Deoxy-β-D-allofuranosyl)-6-methylpurine [methyl(allo)-MePR, 18] and 9-(6-deoxy-α-L-talofuranosyl)-6-methylpurine [methyl(talo)-MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)-MePR] and [methyl(talo)-MePR] are described. The glycosyl donors, 1,2-di-O-acetyl-3,5-di-O-benzyl-α-D-allofuranose (12) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-α-L-talofuranose (16) were prepared from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (4) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6-methylpurine (3), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Preparation of 6-methylpurine Basic Protocol 2: Preparation of the D-allofuranose derivative (12) Basic Protocol 3: Preparation of 6-deoxy-α-L-talofuranoside Basic Protocol 4: Preparation of methyl(allo)-MePR (18) Basic Protocol 5: Preparation of methyl(talo)-MePR (21).

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来源期刊
Current Protocols in Nucleic Acid Chemistry
Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry
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期刊介绍: Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.
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