(R)-4-((S)-3,3-diethoxy-1-hydroxypropyl)-1,3-oxathiolane-2-thione | 138560-04-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧硫杂环戊烷
• 英文名称: (R)-4-((S)-3,3-diethoxy-1-hydroxypropyl)-1,3-oxathiolane-2-thione
• 英文别名: (4R)-4-[(1S)-3,3-diethoxy-1-hydroxy-propyl]-1,3-oxathiolane-2-thione；(4R)-4-[(1S)-3,3-diethoxy-1-hydroxypropyl]-1,3-oxathiolane-2-thione
• CAS: 138560-04-0
• 化学式: C₁₀H₁₈O₄S₂
• 分子量: 266.383
• InChiKey: JEWSOKJFFIJVSC-JGVFFNPUSA-N

物化性质

• 沸点：
  401.6±25.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-4-((S)-3,3-diethoxy-1-hydroxypropyl)-1,3-oxathiolane-2-thione 在 2,6-二甲基吡啶 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 (3S,4S)-3-(tert-butyldimethylsilyl)oxy-4,5-epithiopentanal diethyl acetal
  参考文献：
  名称：

  Asymmetric synthesis of D- and L-2-deoxy-4-thioriboscs

  摘要：

  Both D- and L-enantiomers of 2-deoxy-4-thioribose derivatives 12 and 17 were prepared stereospecifically in 12 steps from 1,3-propanediol. The key intermediary 2,3-epoxy alcohols, 8 and 15 were obtained with high enantiomeric excess by the Sharpless asymmetric epoxidation using (+)-L-diethyl tartrate and (-)-D-diethyl tartrate.

  DOI：

  10.1016/s0957-4166(00)80489-9
• 作为产物：
  描述：

  3,3-diethoxypropanal 在 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 L-(+)-酒石酸二乙酯 、 sodium hydride 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 (R)-4-((S)-3,3-diethoxy-1-hydroxypropyl)-1,3-oxathiolane-2-thione
  参考文献：
  名称：

  Asymmetric synthesis of D- and L-2-deoxy-4-thioriboscs

  摘要：

  Both D- and L-enantiomers of 2-deoxy-4-thioribose derivatives 12 and 17 were prepared stereospecifically in 12 steps from 1,3-propanediol. The key intermediary 2,3-epoxy alcohols, 8 and 15 were obtained with high enantiomeric excess by the Sharpless asymmetric epoxidation using (+)-L-diethyl tartrate and (-)-D-diethyl tartrate.

  DOI：

  10.1016/s0957-4166(00)80489-9

文献信息

• The development of β-selective glycosylation reactions with benzyl substituted 2-deoxy-1,4-dithio-D-<i>erythro</i>-pentofuranosides: enabling practical multi-gram syntheses of 4'-Thio-2'-deoxycytidine (T-dCyd) and 5-aza-4’-thio-2’-deoxycytidine (aza-T-dCyd) to support clinical development
  作者：Donn G. Wishka、Omar D. Lopez、Vladimir F. Rudchenko、Guangfei Huang、Robert Bahde、Vineet Kumar、Sergiy M. Denysenko、Lianhao Zhang、Mianji Zhang、Beverly A. Teicher、Joel Morris

  DOI：10.1080/15257770.2020.1832694

  日期：2021.1.2

  perform direct β-selective glycosylation reactions with 2-deoxy-1,4-dithio-D-erythro-pentofuranosides has long been a significant stumbling block for the multi-gram synthesis of 4’-thio-2’-deoxy nucleosides. In addition, previously reported methods for the preparation of appropriately substituted 2-deoxy-1,4-dithio-D-erythro-pentofuranosides have proven problematic for large scale synthesis. To address

  摘要 长期以来，缺乏与 2-deoxy-1,4-dithio-D-erythro-pentofuranosides 进行直接 β-选择性糖基化反应的有效方法一直是多克合成 4'-thio-2 的重要障碍。 '-脱氧核苷。此外，先前报道的制备适当取代的 2-deoxy-1,4-dithio-D-erythro-pentofuranosides 的方法已证明对大规模合成存在问题。为了解决这些问题，我们在本文中描述了对先前报道的方法的修改和优化，以方便地大规模合成苄基取代的 2-脱氧-1,4-二硫代-D-赤型-戊呋喃糖苷。此外，我们描述了苄基取代的 2-deoxy-1 的 β-选择性糖基化反应的反应条件的发展，4-dithio-D-erythro-pentofuranosides 与 N4-benzoylcytosine 和 5-aza-cytosine，使临床候选物 4'-thio-2'-deoxycytidine
• Stereocontrolled preparation of cyclic xanthate; a novel synthetic route to 4-thiofuranose and 4′-thionucleoside
  作者：Jun'ichi Uenishi、Mitsuhiro Motoyama、Yoshitaka Nishiyama、Shoji Wakabayashi

  DOI：10.1039/c39910001421

  日期：——

  Optically active cyclic xanthate was prepared by the reaction of an epoxy alcohol with NaH and CS2, and was found to be a useful intermediate for synthesis of 4-thio-2-deoxyribose and 4′-thio-2′-deoxyribonucleoside.

  通过环氧醇与 NaH 和 CS2 的反应制备了具有光学活性的环黄原酸盐，并发现它是合成 4-硫代-2-脱氧核糖和 4â²-硫代-2â²-脱氧核苷的有用中间体。
• Stereoselective synthesis and process for the manufacturing of 2′-deoxynucleosides
  申请人：The USA, as represented by the Secretary, Department of Health and Human Services

  公开号：US11365211B2

  公开（公告）日：2022-06-21

  Methods for stereoselective synthesis and manufacturing of 2′-deoxynucleosides, such as 2′-ribonucleosides, are disclosed. In some embodiments, the 2′-deoxynucleoside is a β-anomer of a 2′-deoxynucleoside having a 3′ α hydroxyl, 4′ β hydroxymethyl configuration. Nonlimiting examples of compounds prepared by the disclosed methods include 4′-thio-2′-deoxycytidine (T-dCyd) and 5-aza-4′-thio-2′-deoxycytidine (5-aza-T-dCyd; aza-T-dCyd; aza-T-dC).

  本发明公开了立体选择性合成和制造 2′-脱氧核苷（如 2′-核糖核苷）的方法。在某些实施方案中，2′-脱氧核苷是具有 3′ α羟基、4′ β羟甲基构型的 2′-脱氧核苷的 β-异构体。用所公开的方法制备的化合物的非限制性实例包括 4′-硫代-2′-脱氧胞苷（T-dCyd）和 5-氮杂-4′-硫代-2′-脱氧胞苷（5-氮杂-T-dCyd；氮杂-T-dCyd；氮杂-T-dC）。
• [EN] STEREOSELECTIVE SYNTHESIS AND PROCESS FOR THE MANUFACTURING OF 2'-DEOXYNUCLEOSIDES<br/>[FR] SYNTHÈSE STÉRÉOSÉLECTIVE ET PROCÉDÉ DE FABRICATION DE 2'-DÉSOXYNUCLÉOSIDES
  申请人：US HEALTH

  公开号：WO2019152459A8

  公开（公告）日：2019-10-03
• STEREOSELECTIVE SYNTHESIS AND PROCESS FOR THE MANUFACTURING OF 2'-DEOXYNUCLEOSIDES
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Services

  公开号：EP3746452A1

  公开（公告）日：2020-12-09