(2R,3S,4S)-3,4-双(苄氧基)-2-((苄氧基)甲基)四氢噻吩 | 187590-77-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2R,3S,4S)-3,4-双(苄氧基)-2-((苄氧基)甲基)四氢噻吩
• 英文名称: 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-D-arabinitol
• 英文别名: (2R,3S,4S)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydrothiophene；2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-epithio-d-arabinitol；(2R,3S,4S)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)thiolane
• CAS: 187590-77-8
• 化学式: C₂₆H₂₈O₃S
• 分子量: 420.573
• InChiKey: IISDOLHHPNAZII-CYXNTTPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S)-3,4-双(苄氧基)-2-((苄氧基)甲基)四氢噻吩 在 三氟甲磺酸三甲基硅酯 、 4 A molecular sieve 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 9-[(3S,4S,5R)-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)thiolan-2-yl]purin-6-amine
  参考文献：
  名称：

  A Facile, Alternative Synthesis of 4‘-Thioarabinonucleosides and Their Biological Activities

  摘要：

  4'-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from D-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hydroxyl groups to give 1-O-acetyl-4-thioarabinose (II), which was condensed with nucleobases to give 4'-thioarabinonucleosides. The 5-substituted-4'-thioaraU (6a-e) derivatives showed anti-HSV-1 activity (ED50 = 0.43-3.50 mu g/mL). 4'-ThioaraG (6h) and 2,6-diaminopurine 4'-thioarabinonucleoside (4'-thioaraDAP, 6g) showed antiviral activity against several herpes viruses and were particularly potent against human cytomegalovirus (0.010 and 0.022 mu g/mL, respectively).

  DOI：

  10.1021/jm9701536
• 作为产物：
  描述：

  (2R,3S,4S)-2,3,5-tri(benzyloxy)-1,4-di(methylsulfonyloxy)pentane 在 sodium sulfide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S,4S)-3,4-双(苄氧基)-2-((苄氧基)甲基)四氢噻吩
  参考文献：
  名称：

  GLYCOSIDASE INHIBITORS AND METHODS OF SYNTHESIZING SAME

  摘要：

  本发明的化合物涉及与salacinol的链延伸和链修饰类似物，包括其中硫酸酯基团已被羧酸酯基团或磷酸酯基团取代的实施例。在其他实施例中，硫酸酯基团在带电离结构中已被向一碳原子移位。在另一实施例中，多羟基侧链可以被脂溶性烷基链和适当的对离子取代。本发明还涵盖了合成salacinol类似物的方法以及将这些类似物用于酶抑制应用的方法。

  公开号：

  US20070244184A1

文献信息

• Design, synthesis and biological evaluation of 3′-benzylated analogs of 3′-epi-neoponkoranol as potent α-glucosidase inhibitors
  作者：Dan Liu、Weigang He、Zihao Wang、Long Liu、Chengqian Wang、Chenxi Zhang、Chengcheng Wang、Yuxuan Wang、Genzoh Tanabe、Osamu Muraoka、Xiaoming Wu、Liang Wu、Weijia Xie

  DOI：10.1016/j.ejmech.2016.01.029

  日期：2016.3

  substituent and particularly the ortho-substituted trifluoromethyl on benzyl group with the adjacent hydrophobic amino residues. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the synthesized sulfonium salts against normal cell line. The enzyme kinetic studies showed a fully competitive inhibition of these sulfonium salts on each α-glucosidase.

  设计并合成了一组在侧链部分的3'-位置连接有不同疏水取代基的3'-表位-新烯醇分子类似物，以进一步提高对α-葡萄糖苷酶的抑制活性。这些化合物的生物学评估表明，与邻位取代的苄基连接的sulf盐显示出最佳的α-葡萄糖苷酶抑制活性。最有效的化合物10i表现出比所有天然产物更大的抑制活性。此外，在10i上的对接研究ntMGAM与ntMGAM提出了一种新的结合模式，表明氨基残基Asp542应该是小分子对α-葡萄糖苷酶的强抑制活性的关键相互作用点。10i最强的α-葡萄糖苷酶抑制活性可以通过与3'相连的取代基，特别是苄基上的邻位取代的三氟甲基与相邻的疏水氨基残基之间的范德华相互作用来合理化。细胞毒性评估分析表明，合成的salts盐对正常细胞系具有很高的安全性。酶动力学研究表明，这些sulf盐对每种α-葡萄糖苷酶均具有完全竞争性抑制作用。
• Elongation of the side chain by linear alkyl groups increases the potency of salacinol, a potent α-glucosidase inhibitor from the Ayurvedic traditional medicine “Salacia,” against human intestinal maltase
  作者：Katsuki Takashima、Mika Sakano、Eri Kinouchi、Shinya Nakamura、Shinsuke Marumoto、Fumihiro Ishikawa、Kiyofumi Ninomiya、Isao Nakanishi、Toshio Morikawa、Genzoh Tanabe

  DOI：10.1016/j.bmcl.2020.127751

  日期：2021.2

  R = C6H13, c: R = C8H17, d: R = C10H21) to the side chains of salacinol (1), a natural α-glucosidase inhibitor from Ayurvedic traditional medicine “Salacia”, were synthesized. The α-glucosidase inhibitory activities of all the synthesized analogs were evaluated in vitro. Against human intestinal maltase, the inhibitory activities of 12a and 13a with seven-carbon side chain were equal to that of 1. In contrast

  通过引入烷基（a：R = C 3 H 7，b R = C 6 H 13，c：R = ）四个扩链类似物（12a - 12d）和两个相关的脱O-磺化类似物（13a和13c）。C 8 H 17，d：R = C 10 H 21）到Salacinol（1）的侧链上，Salacinol（1）是阿育吠陀传统药物“ Salacia ”中的天然α-葡萄糖苷酶抑制剂”，进行了合成。在体外评估了所有合成类似物的α-葡萄糖苷酶抑制活性。对人肠道麦芽糖酶的抑制作用，具有7个碳侧链的12a和13a的抑制活性等于1。相反，类似物（12b – 12d和13c）对相同的酶表现出比1高的抑制活性，并且与临床上使用的抗糖尿病药，伏格列波糖，阿卡波糖和米格列醇相比具有相同或更高的效力。因此，1的侧链伸长 对特异性增加对人肠麦芽糖酶的抑制活性是有效的。
• Glycosidase inhibitors and methods of synthesizing same
  申请人：Pinto Mario Brian

  公开号：US20050065139A1

  公开（公告）日：2005-03-24

  A method for synthesizing Salacinol, its stereoisomers, and analogues, homologues and other derivatives thereof potentially useful as glycolsidase inhibitors. The compounds of the invention may have the general formula (I) or (II): The synthetic schemes comprise reacting a cyclic sulfate with a 5-membered ring sugar containing a heteroatom (X). The heteroatom preferably comprises sulfur, selenium, or nitrogen. The cyclic sulfate and ring sugar reagents may be readily prepared from carbohydrate precursors, such as D-glucose, L-glucose, D-xylose and L-xylose. The target compounds are prepared by opening of the cyclic sulfates by nucleophilic attack of the heteroatoms on the 5-membered ring sugars. The resulting heterocyclic compounds have a stable, inner salt structure comprising a heteroatom cation and a sulfate anion. The synthetic schemes yield various stereoisomers of the target compounds in moderate to good yields with limited side-reactions.

  一种合成Salacinol及其立体异构体、类似物、同系物和其他衍生物的方法，可能用作糖苷酶抑制剂。本发明的化合物可能具有一般式(I)或(II)：合成方案包括将环状硫酸酯与含有杂原子(X)的5元环糖反应。杂原子优选包括硫、硒或氮。环状硫酸酯和环糖试剂可以从碳水化合物前体（如D-葡萄糖、L-葡萄糖、D-木糖和L-木糖）中轻松制备。目标化合物是通过杂原子对5元环糖的亲核攻击打开环状硫酸酯来制备的。所得的杂环化合物具有稳定的内盐结构，包括一个杂原子阳离子和一个硫酸酯阴离子。合成方案以中等至良好的产率产生目标化合物的各种立体异构体，副反应有限。
• Improved Syntheses of the Naturally Occurring Glycosidase Inhibitor Salacinol
  作者：B. Pinto、Ahmad Ghavami、Kashinath Sadalapure、Blair Johnston、Mercedes Lobera、Barry Snider

  DOI：10.1055/s-2003-40353

  日期：——

  Improved syntheses of the naturally occurring sulfonium ion, salacinol are described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of Type 2 Diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl- or 2,3,5-tri-O-p-methoxybenzyl- 1 ,4-anhydro-4-thio-D-arabinitol

  描述了天然存在的锍离子、salacinol 的改进合成。Salacinol 是斯里兰卡和印度传统上用于治疗 2 型糖尿病的五层龙水提取物中的活性成分之一。合成策略至少依赖于 2,3,5-tri-O-benzyl- 或 2,3,5-tri-Op-methoxybenzyl-1,4-anhydro-4-thio-D-arabinitol 的亲核攻击苯亚甲基保护的 L-赤藓糖醇-1,3-环硫酸盐在 1,1,1,3,3,3-六氟-2-丙醇中的受阻碳作为溶剂。将这些反应与苄基保护的 L-赤藓糖醇-1.3-环硫酸盐以及丙酮和 2-丙醇中的反应进行比较。与亚苄基保护的环状硫酸盐的反应获得了极好的产率。
• Diastereoselective Synthesis of Salacinol-Type α-Glucosidase Inhibitors
  作者：Fumihiro Ishikawa、Kazumi Jinno、Eri Kinouchi、Kiyofumi Ninomiya、Shinsuke Marumoto、Weijia Xie、Osamu Muraoka、Toshio Morikawa、Genzoh Tanabe

  DOI：10.1021/acs.joc.7b02566

  日期：2018.1.5

  A facile and highly diastereoselective approach toward the synthesis of potent salacinol-type α-glucosidase inhibitors, originally isolated from plants of the genus “Salacia”, was developed using the S-alkylation of thiosugars with epoxides in HFIP (∼90%, dr, α/β = ∼ 26/1). The dr ratio of the product was significantly improved by the protocol as compared to that of the conventional S-alkylation of

  在HFIP中使用硫糖与环氧化物的S-烷基化反应开发了一种简便有效的非对映选择性方法，用于合成强效的柳杉醇型α-葡萄糖苷酶抑制剂（最初从“ Salacia ”属植物中分离）。 α/β=约26/1）。通过该方案，与常规的硫糖的S-烷基化反应相比，产物的dr比率显着提高（dr，α/β＝〜8/1）。该方案可用于所需化合物的克规模合成。3'- Ô -benzylated的Salacinol类似物，其是最有效的体外抑制剂至今，合成并评价体内; 所有类似物都能抑制麦芽糖负荷小鼠的血糖水平，其水平与抗糖尿病药伏格列波糖的水平相当。