3-(2-deoxy-β-D-erythro-pentofuranosyl)-8-hydroxy-6(S)-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one | 85405-01-2

• 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: 3-(2-deoxy-β-D-erythro-pentofuranosyl)-8-hydroxy-6(S)-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one
• 英文别名: (6S)-3-(2-deoxy-β-D-erythro-pentofuranosyl)-8-hydroxy-6-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one；(6S,8S)-8-hydroxy-3-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one；(6S,8S)-8-hydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
• CAS: 85405-01-2
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: DKBDYPZFCQIHPX-GENCIFFESA-N

物化性质

• 沸点：
  724.7±70.0 °C(Predicted)
• 密度：
  1.93±0.1 g/cm3(Predicted)

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

• 作为反应物：
  描述：

  3-(2-deoxy-β-D-erythro-pentofuranosyl)-8-hydroxy-6(S)-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one 在 ammonium hydroxide 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 24.17h， 生成 2-(3-amino-(1S)-methylpropyl)-2'-deoxyguanosine
  参考文献：
  名称：

  由丙烯醛和巴豆醛形成的 DNA 链间交联

  摘要：

  丙烯醛和更高的 α,β-不饱和醛是双功能基因毒素。丙烯醛的脱氧鸟苷加合物，3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)-propanodeoxyguanosine, 2a) 是由丙烯醛形成的主要 DNA 加合物。通过 HPLC、CZE、MALDI-TOF 和熔解现象评估含有 2a 的寡脱氧核苷酸双链体形成链间交联的潜力。链间交联是 DNA 中最严重的损伤类型之一，因为它们是复制的绝对障碍。在包含序列 5'-dC-2a 的寡聚脱氧核苷酸中，交联以缓慢、可逆的方式发生到大约 50% 的程度。酶消化形成 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-t

  DOI：

  10.1021/ja020778f
• 作为产物：
  描述：

  (2R,3S,5R)-5-[2-氟-6-(2-三甲基硅烷基乙氧基)嘌呤-9-基]-2-(羟基甲基)四氢呋喃-3-醇 在 sodium periodate 、 phosphate buffer 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 8.17h， 生成 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

• 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
• Metabolic Profiling of Chronic Cadmium Exposure in the Rat
  作者：Julian L. Griffin、Lee A. Walker、Richard F. Shore、Jeremy K. Nicholson

  DOI：10.1021/tx015521u

  日期：2001.10.1

  A confounding problem with studying the effects of environmental exposure to contaminants in wild populations is that analytical techniques are invasive, particularly where the physiological effects of the toxin are assessed. In this study, a metabonomic approach to investigate the biochemical effects of chronic oral exposure to environmentally realistic doses of CdCl2 (low, 8 mg/kg; high, 40 mg/kg) is presented. H-1 NMR spectra of urine from exposed animals were analyzed using pattern recognition methods to identify biomarkers for a 94 day exposure period. Creatinuria and both increased excretion and complexation of citrate was detected after 19 days of exposure in both exposure groups. This was accompanied by a decrease in plasma Ca2+/Mg2+ ratio in blood plasma after 94 days. Post mortem, magic angle spinning (MAS) H-1 NMR spectroscopy was used alongside conventional analytical techniques to investigate intact tissue directly. According to atomic absorption sectroscopy, kidney tissue accumulated 26.8 +/- 2.5 mug of Cd2+/g dry wt (low) and 75.9 +/- 4.3 mug of Cd2+/g dry wt (high). Using high-resolution MAS H-1 NMR spectroscopy altered lipid content was detected in kidneys from animals exposed to Cd2+. However, unlike acute exposure, no testicular damage was evident. This systemic approach to metabolism demonstrated the different physiological effects of chronic subacute compared with an acute exposure to Cd2+.
• 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.
• DNA Interchain Cross-Links Formed by Acrolein and Crotonaldehyde
  作者：Ivan D. Kozekov、Lubomir V. Nechev、M. Scott Moseley、Constance M. Harris、Carmelo J. Rizzo、Michael P. Stone、Thomas M. Harris

  DOI：10.1021/ja020778f

  日期：2003.1.1

  3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-(N(2)-2'-deoxyguanosinyl)pyrimido[1,2-a]purin-10(3H)one (5a) and reduction with NaCNBH(3) followed by enzymatic digestion to give 1,3-bis(2'-deoxyguanosin-N(2)-yl)propane (6a) established that cross-linking had occurred with the exocyclic amino group of deoxyguanosine. It is concluded that the cross-link is a mixture of imine and carbinolamine structures

  丙烯醛和更高的 α,β-不饱和醛是双功能基因毒素。丙烯醛的脱氧鸟苷加合物，3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)-propanodeoxyguanosine, 2a) 是由丙烯醛形成的主要 DNA 加合物。通过 HPLC、CZE、MALDI-TOF 和熔解现象评估含有 2a 的寡脱氧核苷酸双链体形成链间交联的潜力。链间交联是 DNA 中最严重的损伤类型之一，因为它们是复制的绝对障碍。在包含序列 5'-dC-2a 的寡聚脱氧核苷酸中，交联以缓慢、可逆的方式发生到大约 50% 的程度。酶消化形成 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-t