1,4-二脱氧-1,4-环硫-2,3-O-(异丙亚基)-D-核糖醇 | 596103-06-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1,4-二脱氧-1,4-环硫-2,3-O-(异丙亚基)-D-核糖醇
• 英文名称: ((3aS,4R,6aR)-2,2- dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)methanol
• 英文别名: ((3aS,4R,6aR)-2,2-Dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)methanol；[(3aS,4R,6aR)-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-4-yl]methanol
• CAS: 596103-06-9
• 化学式: C₈H₁₄O₃S
• 分子量: 190.263
• InChiKey: YCABSTBYVZTCQI-XVMARJQXSA-N

物化性质

• 熔点：
  56-60 °C
• 沸点：
  301.2±32.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  64
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

1,4-脱水-2,3-二-O-异亚丙基-4-硫基-D-核糖醇是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，特别是针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等作用[1]。

反应信息

• 作为反应物：
  描述：

  1,4-二脱氧-1,4-环硫-2,3-O-(异丙亚基)-D-核糖醇 在 碳酸氢钠 、 2-碘酰基苯甲酸 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 38.33h， 生成 tert-butyl(((3aS,6aR)-2,2-dimethyldihydrothieno[3,4-d][1,3]dioxol-4(3aH)-ylidene)methoxy)dimethylsilane
  参考文献：
  名称：

  Synthesis of 4′-Ethynyl-2′-deoxy-4′-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI

  摘要：

  The synthesis of 4'-ethynyl-2'-deoxy-4'-thioribonucleosides was carried out utilizing an electrophilic glycosidation in which 4-ethynyl-4-thiofuranoid glycal 16 served as a glycosyl donor. Electrophilic glycosidation between 16 and the silylated nucleobases (N-4-acetylcytosine, N-6-benzoyladenine, and N-2-acetyl-O-6-diphenylcarbamoylguanine) was carried out in the presence of N-iodosuccinimide (NIS), leading to the exclusive formation of the desired beta-anomers 29, 33, and 36. Anti-HIV studies demonstrated that these 4'-thio nucleosides were less cytotoxic to T-lymphocyte (i.e., MT-4 cells) than the corresponding 4'-ethynyl derivatives of 2'-deoxycytidine (44), 2'-deoxyadenosine (45), and 2'-deoxyguanosine (46). Comparison of the selectivity indices (SI) was made between 4'-thionucleosides (32, 41, and 43) and the corresponding 4'-oxygen analogues 44-46 by using the reported CC50 and EC50 values. In the case of cytosine and adenine nucleosides, comparable SI values were obtained as follows: 32 (545) and 44 (458); 41 (>230) and 45 (1630). In contrast, 4'-ethynyl-2'-deoxy-4'-thioguanosine 43 was found to possess a SI value of >18200, which is 20 times better than that of 46 (933).

  DOI：

  10.1021/ml2001054
• 作为产物：
  描述：

  2,3:5,6-di-O-isopropylidene-D-gulitol 在 吡啶 、 lead(IV) acetate 、 sodium sulfide 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.67h， 生成 1,4-二脱氧-1,4-环硫-2,3-O-(异丙亚基)-D-核糖醇
  参考文献：
  名称：

  N⁶-Substituted D-4‘-Thioadenosine-5‘-methyluronamides:  Potent and Selective Agonists at the Human A₃ Adenosine Receptor

  摘要：

  4'-Thio analogues 3-5 of Cl-IB-MECA (2) (K-i = 1.0 +/- 0.2 nM at the human A(3) adenosine receptor) were synthesized from D-gulono-gamma-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4-thionucleosides exhibited higher binding affinity to the human A(3) adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (K-i = 0.28 +/- 0.09 nM). 4 was also selective for A(3) vs human A(1) and human A(2A) receptors by 4800- and 36000-fold, respectively.

  DOI：

  10.1021/jm034098e

文献信息

• Purine nucleosides
  申请人：Jeong Shin Lak

  公开号：US20050256143A1

  公开（公告）日：2005-11-17

  Disclosed are purine nucleoside compounds that are selective to A 3 adenosine receptors and are useful for the treatment of cancer and inflammatory diseases. The compounds are shown by the following general formula (I), including isomers thereof: wherein X is sulfur or oxygen; R 1 is hydrogen, alkyl, benzyl, halobenzyl, or phenylalkyl; R 2 is hydrogen, halogen, alkoxy, alkenyl, alkynyl, alkylthio, or thio; R 3 and R 3′ are hydrogen, hydroxyalkyl, alkoxycarbonyl, or alkylaminocabonyl, whereas R 3 and R 3 ′ do not have identical substituents simultaneously; and R 4 is hydrogen or alkyl. Also disclosed are a pharmaceutical composition comprising a compound of formula (I), an isomer, or its pharmacologically acceptable salt as an active ingredient and a method for preventing or treating various diseases, state, or condition, including asthma, inflammation, cerebral ischemia, heart diseases, and cancer.

  揭示了对A3腺苷受体具有选择性的嘌呤核苷化合物，可用于治疗癌症和炎症性疾病。所述化合物由以下一般式（I）表示，包括其异构体：其中X为硫或氧；R1为氢、烷基、苄基、卤代苄基或苯基烷基；R2为氢、卤素、烷氧基、烯基、炔基、烷基硫基或硫基；R3和R3'为氢、羟基烷基、烷氧羰基或烷基氨羰基，其中R3和R3'不同时具有相同的取代基；R4为氢或烷基。还揭示了一种包含一种式（I）的化合物、其异构体或其药理学上可接受的盐作为活性成分的药物组合物，以及一种用于预防或治疗各种疾病、状态或症状的方法，包括哮喘、炎症、脑缺血、心脏疾病和癌症。
• Biosynthetic Origin of the Atypical Stereochemistry in the Thioheptose Core of Albomycin Nucleoside Antibiotics
  作者：Richiro Ushimaru、Hung-wen Liu

  DOI：10.1021/jacs.8b12565

  日期：2019.2.13

  d-ribofuranose ring and an l-amino acid moiety. The conversion of l-to d-amino acid configuration is catalyzed by the PLP-dependent epimerase AbmD. The d- ribo to d- xylo conversion of the thiofuranose ring appears according to gene deletion experiments to be mediated by AbmJ, which is annotated as a radical S-adenosyl-l-methionine (SAM) enzyme. These studies establish several key steps in the assembly of the

  白霉素是肽基硫代核苷天然产物，对临床上重要的病原体显示出抗菌活性。它们的结构以具有非典型立体化学的硫庚糖为特征，包括用 d-氨基酸部分修饰的 d-呋喃木糖环。在本文中证明，AbmH 是一种依赖于 5'-磷酸 (PLP) 的吡哆醛转醛缩酶，其催化苏式选择性醛醇型反应以生成具有 d-呋喃核糖环和 l-氨基酸部分的硫庚糖核心。L-氨基酸构型向d-氨基酸构型的转化由PLP依赖性差向异构酶AbmD催化。根据基因缺失实验，硫代呋喃糖环从 d-核糖到 d-木糖的转化似乎是由 AbmJ 介导的，AbmJ 被注释为自由基 S-腺苷-l-甲硫氨酸 (SAM) 酶。
• [EN] PRMT5 INHIBITORS<br/>[FR] INHIBITEURS DE PRMT5
  申请人：MERCK SHARP & DOHME

  公开号：WO2020033282A1

  公开（公告）日：2020-02-13

  The present invention provides a compound of Formula (I) Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

  本发明提供了化合物式(I)的化合物，或其药用可接受的盐，这些化合物是PRMT5抑制剂。
• Synthesis and Properties of 4′-ThioLNA/BNA
  作者：Rion Maeda、Noriko Saito-Tarashima、Hideaki Wakamatsu、Yoshihiro Natori、Noriaki Minakawa、Yuichi Yoshimura

  DOI：10.1021/acs.orglett.1c01306

  日期：2021.5.21

  applicable to oligonucleotide therapeutics, we designed a 4′-thio analogue of an LNA/BNA monomer. Synthesis of 4′-hydroxymethyl-4′-thioribonucleoside was achieved by a tandem ring-contraction-aldol reaction of a 5-thiopyranose derivative and the subsequent Pummerer-type thioglycosylation reaction of the corresponding sulfoxide. Treatment of 4′-hydroxymethyl-4′-thiopyrimidine nucleosides with diphenyl

  为了开发适用于寡核苷酸治疗的新核苷类似物，我们设计了LNA / BNA单体的4'-硫代类似物。4'-羟甲基-4'-硫代核糖核苷的合成是通过5-硫代吡喃糖衍生物的串联环缩合-醛醇缩合反应和随后的相应亚砜的Pummerer型硫代糖基化反应实现的。在催化NaHCO 3存在下用碳酸二苯酯处理4'-羟甲基-4'-硫代嘧啶核苷，得到所需的4'-thioLNA / BNA单体，将其引入寡核苷酸中。
• [EN] 4-THIORIBOSE NAD ANALOGUES AND METHODS OF SYNTHESIZING AND USING THE SAME<br/>[FR] ANALOGUES DU 4-THIORIBOSE NAD ET PROCÉDÉS DE SYNTHÈSE ET D'UTILISATION DE CEUX-CI
  申请人：UNIV SOUTHERN CALIFORNIA

  公开号：WO2020073026A1

  公开（公告）日：2020-04-09

  This disclosure provides a method of synthesis of 4'-thioribose NAD+ and analogues thereof, using an efficient chemoenzymatic approach. Also provided are methods of inhibiting the CD38 enzyme and compounds including 4'-thioribose NAD+ and compounds related thereto.

  本公开提供了一种合成4'-硫核糖NAD+及其类似物的方法，使用高效的化学酶法途径。还提供了抑制CD38酶的方法和包括4'-硫核糖NAD+及相关化合物的化合物。