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{"title":"Synthesis of 9-(6-Deoxy-α-L-Talofuranosyl)-6-Methylpurine and 9-(6-Deoxy-β-D-Allofuranosyl)-6-Methylpurine Nucleosides.","authors":"Abdalla E A Hassan, Reham A I Abou-Elkhair, Hend M Maaroof, John A Secrist","doi":"10.1002/cpnc.105","DOIUrl":null,"url":null,"abstract":"<p><p>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).</p>","PeriodicalId":10966,"journal":{"name":"Current Protocols in Nucleic Acid Chemistry","volume":"81 1","pages":"e105"},"PeriodicalIF":0.0000,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cpnc.105","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Protocols in Nucleic Acid Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/cpnc.105","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Chemistry","Score":null,"Total":0}
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Abstract
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).
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
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)。
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