1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pento-2-enofuranosyl>thymine | 125440-17-7

• 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: 1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pento-2-enofuranosyl>thymine
• 英文别名: 1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl>thymine；1-<5-(O-t-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl>thymine；5'-O-(tert-butyldiphenylsilyl)-2',3'-didehydro-3'-deoxythymidine；5'-O-(tert-butyldiphenylsilyl)-d4T；1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pento-2-enofuranosyl]thymine；1-[(2R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 125440-17-7
• 化学式: C₂₆H₃₀N₂O₄Si
• 分子量: 462.621
• InChiKey: RVBRKFJQVLALSE-NZQKXSOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pento-2-enofuranosyl>thymine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以100%的产率得到司他夫定
  参考文献：
  名称：

  从 2',2'-双（苯硫基）核苷类似物合成 2',3'-Didehydro-2',3'-双脱氧核苷

  摘要：

  2',3'-Didehydro-2',3'-dideoxy 核苷是由 2',2'-双（苯硫基）核苷类似物通过五步反应合成的。通过用钠汞齐处理除去中间体的磺酰基。

  DOI：

  10.1246/bcsj.68.2327
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 三正丁胺 、 四氯化锡 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 xylene 为溶剂， 反应 11.0h， 生成 1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-glycero-pento-2-enofuranosyl>thymine
  参考文献：
  名称：

  Synthesis of 2',3'-Didehydro-2',3'-dideoxynucleosides Utilizing Coupling Reactions between Nucleic Bases and Phenylthio-substituted 2,3-Dideoxyribose

  摘要：

  Stereoselectivities in coupling reactions between silylated pyrimidine bases and 3- or 2-alpha-phenylthio-2,3-dideoxyribose were examined. In the former case, no stereoselectivies were observed when the coupling reactions were performed either with 1-chlorosugar in an S(N)2 mode or in the presence of Lewis acids as catalyst in an S(N)1 mode. Coupling reaction with 2-alpha-phenylthio-2,3-dideoxyribose in the presence of Lewis acids, especially SnCl4, proceeded with good stereoselectivity to give anomeric mixtures of alpha:beta = 1:9. All these nucleosides were converted to 2',3'-didehydro-2',3'-dideoxynucleosides by oxidation to sulfoxides followed by thermal elimination of sulfenic acid.

  DOI：

  10.3987/com-91-5884

文献信息

• Simple Entry to 3‘-Substituted Analogues of Anti-HIV Agent Stavudine Based on an Anionic O → C Stannyl Migration
  作者：Hiroki Kumamoto、Hiromichi Tanaka

  DOI：10.1021/jo0107958

  日期：2002.5.1

  hydrogens (H-3' and H-2'). When the lithiation of the 5'-O-tert-butyldiphenylsilyl derivative 5 was carried out in the presence of HMPA, an anionic silyl migration took place to give the 3'-C-silylated product 4a. The stannyl version of this reaction was found to be also possible, which has disclosed a highly simple entry to the d4T analogues variously substituted at the 3'-position by manipulating

  研究了抗HIV药物司他夫定（d4T）的5'-O保护衍生物与LTMP的反应，目的是锂化乙烯基氢（H-3'和H-2'）。当5′-O-叔丁基二苯基甲硅烷基衍生物5的锂化在HMPA存在下进行时，发生阴离子甲硅烷基迁移，得到3′-C-甲硅烷基化产物4a。发现该反应的亚锡烷基形式也是可能的，其已经公开了通过操纵3'-C-锡烷基d4T作为共同中间体而非常简单地进入在3'-位被各种取代的d4T类似物。
• A general method for controlling glycosylation stereochemistry in the synthesis of 2′-deoxyribose nucleosides
  作者：Lawrence J. Wilson、Dennis Liotta

  DOI：10.1016/s0040-4039(00)98793-8

  日期：1990.1

  Glycosylation reactions of 2-arylsulfinyl-O-acetylribosides6 with silylated thymine11 produce 2′-deoxyribose nucleosides with high β-selectivity. An application of this directing effect in the synthesis of the antiretroviral agent D4T,2, is described.

  2-芳基亚磺酰基-O-乙酰基核糖苷6与甲硅烷基化的胸腺嘧啶11的糖基化反应产生具有高β-选择性的2'-脱氧核糖核苷。描述了这种指导作用在抗逆转录病毒药D4T，2的合成中的应用。
• Stereoselective Synthesis of 2‘-Amino-2‘,3‘-dideoxynucleosides by Nitrone 1,3-Dipolar Cycloaddition:  A New Efficient Entry Toward d4T and Its 2-Methyl Analogue
  作者：Ugo Chiacchio、Antonio Rescifina、Daniela Iannazzo、Giovanni Romeo

  DOI：10.1021/jo972264i

  日期：1999.1.1

  2'-(dimethylamino)-2',3'-dideoxynucleosides is reported. The synthetic strategy relies on the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to allyl acetate, followed by reductive ring opening to substituted lactones, DIBALH reduction to the corresponding 3-(dimethylamino)tetrahydro-2-furanols, and coupling with silylated thymine. The removal of the dimethylamino group by Cope elimination affords a new formal

  据报道有效获得2'-（二甲基氨基）-2'，3'-二脱氧核苷。合成策略依赖于将C-烷氧羰基硝酮与乙酸烯丙酯进行1,3-偶极环加成，然后将开环还原成取代的内酯，将DIBALH还原为相应的3-（二甲氨基）四氢-2-呋喃醇，然后与甲硅烷基化偶联胸腺嘧啶。通过Cope消除去除二甲基氨基基团提供了d4T和类似的不饱和2'，3'-二脱氧核苷的新形式合成。
• Stereoselective Synthesis of 2‘,3‘-Dideoxynucleosides by Addition of Selenium Electrophiles to Glycals. A Formal Synthesis of D4T from 2-Deoxyribose
  作者：Yolanda Díaz、Anas El-Laghdach、M Isabel Matheu、Sergio Castillón

  DOI：10.1021/jo9616825

  日期：1997.3.1
• A highly stereoselective synthesis of anti-HIV 2',3'-dideoxy- and 2',3'-didehydro-2',3'-dideoxynucleosides
  作者：J. Warren Beach、Hea O. Kim、Lak S. Jeong、Satyanarayana Nampalli、Qamrul Islam、Soon K. Ahn、J. Ramesh Babu、Chung K. Chu

  DOI：10.1021/jo00040a031

  日期：1992.7

  A general total synthetic method for the stereocontrolled synthesis of 2',3'-dideoxy- as well as 2',3'-didehydro-2',3'-dideoxynucleosides is presented. Introduction of an alpha-phenylselenenyl group at the 2-position of 2,3-dideoxyribosyl acetate directs the glycosyl bond formation to give greater-than-or-equal-to 95% beta-isomer. This 2'-phenylselenenyl nucleoside may be converted to either the 2',3'-dideoxynucleoside by treatment with n-Bu3SnH and Et3B at room temperature or to the unsaturated derivative by treatment with H2O2/cat. pyridine. The application of this method to the syntheses of pyrimidines (ddU, ddT, ddC), 6-substituted purines (ddA, ddI, 6-chloro-ddP, N6-Me-ddA), and 2,6-disubstituted purines (2-F-ddA, 6-chloro-2-amino-ddP) as well as selected 2',3'-didehydro-2',3'-dideoxy derivatives is reported.