(6R,8R)-8-hydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (6R,8R)-8-hydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: DKBDYPZFCQIHPX-JDDHQFAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(4,5-dihydroxypentan-2-ylamino)-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one 在 sodium periodate 、 phosphate buffer 作用下， 反应 0.17h， 生成 (6R,8R)-8-hydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one 、 3-(2-deoxy-β-D-erythro-pentofuranosyl)-8-hydroxy-6(S)-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one
  参考文献：
  名称：

  Stereospecific Synthesis of Oligonucleotides Containing Crotonaldehyde Adducts of Deoxyguanosine

  摘要：

  Crotonaldehyde reacts with DNA to form two diastereomeric 1,N-2 cyclic adducts of deoxyguanosine. A synthesis of the two diastereomeric deoxynucleosides has been achieved by reaction of mixed diastereomers of 4-amino-1,2-pentanediol with 2-fluoro-O-6-(trimethylsilylethyl)-deoxyinosine. The resulting N-2-(1-methyl-3,4-dihydroxybutyl)-deoxyguanosine was treated with NaIO4, cleaving the vicinal diol to the aldehyde. Spontaneous cyclization gave the two diastereomers of the crotonaldehyde-adducted nucleoside that were readily separated by HPLC. The absolute configurations were assigned by an enantiospecific synthesis of one diastereomer from (S)-3-aminobutanoic acid. The synthetic strategy has been extended to preparation of a site-specifically adducted oligonucleotide by reaction of the mixed diastereomers of 4-amino-1,2-pentanediol with an 8-mer oligonucleotide containing 2-fluoro-O-6-(trimethylsilylethyl)-deoxyinosine. The diastereomeric oligonucleotides were separated by HPLC and absolute configurations of the adducts were established by enzymatic digestion to the adducted nucleosides.

  DOI：

  10.1021/tx0100690

文献信息

• Reactions of .alpha.-Acetoxy-N-nitrosopyrrolidine and .alpha.-Acetoxy-N-nitrosopiperidine with Deoxyguanosine: Formation of N2-Tetrahydrofuranyl and N2-Tetrahydropyranyl Adducts
  作者：Ruth Young-Sciame、Mingyao Wang、Fung-Lung Chung、Stephen S. Hecht

  DOI：10.1021/tx00046a016

  日期：1995.6

  accounts for part of the THF-dG and THP-dG produced from the alpha-acetoxynitrosamines; stable oxonium ion-derived electrophiles may also be involved in the formation of THF-dG and THP-dG. Comparisons of the yields of various adducts in the reaction of alpha-acetoxyNPYR and alpha-acetoxyNPIP with dG showed some major differences. Whereas yields of THF-dG and THP-dG were similar, adducts formed from open chain

  这项研究的目的是比较α-乙酰氧基-N-亚硝基吡咯烷（α-乙酰氧基NPYR）和α-乙酰氧基-N-亚硝基哌啶（α-乙酰氧基NPIP）与脱氧鸟苷（dG）的反应。α-乙酰氧基NPYR和α-乙酰氧基NPIP是由NPYR和NPIP代谢形成的α-羟基亚硝胺的稳定前体。这些α-羟基亚硝胺被认为是NPYR和NPIP的最接近致癌物。NPYR和NPIP虽然在结构上相似，但具有显着不同的致癌特性，将它们的代谢活化形式与dG和最终DNA的反应进行比较可以提供有关其致癌机理的见解。α-乙酰氧基NPYR和α-乙酰氧基NPIP与dG的反应在37℃和pH 7.0下进行。通过HPLC分析产物，并通过其光谱性质和与标准品的比较来表征。在每个反应中，主要产物之一是新型的dG加合物：由α-乙酰氧基NPYR生成的N2-（四氢呋喃-2-基）dG（THF-dG）和N2-（3,4,5,6-四氢-来自α-乙酰氧基NPIP的2H-吡喃-2-基
• Ultrasensitive Simultaneous Quantification of 1,<i>N</i>²-Etheno-2′-deoxyguanosine and 1,<i>N</i>²-Propano-2′-deoxyguanosine in DNA by an Online Liquid Chromatography−Electrospray Tandem Mass Spectrometry Assay
  作者：Camila C. M. Garcia、Florêncio P. Freitas、Paolo Di Mascio、Marisa H. G. Medeiros

  DOI：10.1021/tx1001018

  日期：2010.7.19

  developed for the simultaneous quantification of 1,N2-etheno-2′-deoxyguanosine (1,N2-εdGuo) and 1,N2-propano-2′-deoxyguanosine (1,N2-propanodGuo) in DNA. This methodology permits direct online quantification of 2′-deoxyguanosine and ca. 500 amol of adducts in 100 μg of hydrolyzed DNA in the same analysis. Using the newly developed technique, accurate determinations of 1,N2-etheno-2′-deoxyguanosine and 1,N2

  由外源性和内源性化合物产生的环外DNA加合物正在成为研究各种人类疾病和空气污染暴露的潜在工具。建立了一种高灵敏度的方法，该方法涉及在线反相高效液相色谱和多反应监测模式下电喷雾串联质谱检测，并采用稳定同位素标记的内标物同时定量1，N 2 -etheno-2'-脱氧鸟苷（1，ñ 2 -εdGuo）和1，ñ 2 -propano -2'-脱氧鸟苷（1，ñ 2-propanodGuo）中的DNA。这种方法可以直接在线定量2'-deoxyguanosine和ca。在同一分析中，在100μg水解的DNA中有500 amol加合物。使用新开发的技术，1，的准确确定Ñ 2 -etheno -2'-脱氧鸟苷和1，Ñ 2在人培养细胞的DNA提取物-propano -2'-脱氧鸟苷的水平（4.01±0.32 1，Ñ 2 -εdGuo / 10 8 dGuo和3.43±0.33 1，N 2 -propanodGuo
• Stereospecific Synthesis of Oligonucleotides Containing Crotonaldehyde Adducts of Deoxyguanosine
  作者：Lubomir V. Nechev、Ivan Kozekov、Constance M. Harris、Thomas M. Harris

  DOI：10.1021/tx0100690

  日期：2001.11.1

  Crotonaldehyde reacts with DNA to form two diastereomeric 1,N-2 cyclic adducts of deoxyguanosine. A synthesis of the two diastereomeric deoxynucleosides has been achieved by reaction of mixed diastereomers of 4-amino-1,2-pentanediol with 2-fluoro-O-6-(trimethylsilylethyl)-deoxyinosine. The resulting N-2-(1-methyl-3,4-dihydroxybutyl)-deoxyguanosine was treated with NaIO4, cleaving the vicinal diol to the aldehyde. Spontaneous cyclization gave the two diastereomers of the crotonaldehyde-adducted nucleoside that were readily separated by HPLC. The absolute configurations were assigned by an enantiospecific synthesis of one diastereomer from (S)-3-aminobutanoic acid. The synthetic strategy has been extended to preparation of a site-specifically adducted oligonucleotide by reaction of the mixed diastereomers of 4-amino-1,2-pentanediol with an 8-mer oligonucleotide containing 2-fluoro-O-6-(trimethylsilylethyl)-deoxyinosine. The diastereomeric oligonucleotides were separated by HPLC and absolute configurations of the adducts were established by enzymatic digestion to the adducted nucleosides.