Acetic acid (2R,3S,4R,5R,6R)-4-acetoxy-2-acetoxymethyl-5-azido-6-bromo-tetrahydro-pyran-3-yl ester | 67817-15-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Acetic acid (2R,3S,4R,5R,6R)-4-acetoxy-2-acetoxymethyl-5-azido-6-bromo-tetrahydro-pyran-3-yl ester
• 英文别名: 3,4,6-Tri-O-Acetyl-2-Azido-2-Deoxy-α-D-Glucopyranosyl Bromide；3,4,6-Tri-O-Acetyl-2-Azido-2-Deoxy-alpha-D-Glucopyranosyl Bromide；[(2R,3S,4R,5R,6R)-3,4-diacetyloxy-5-azido-6-bromooxan-2-yl]methyl acetate
• CAS: 67817-15-6
• 化学式: C₁₂H₁₆BrN₃O₇
• 分子量: 394.179
• InChiKey: MSEDCODCCLBQJH-OOCWMUITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Acetic acid (2R,3S,4R,5R,6R)-4-acetoxy-2-acetoxymethyl-5-azido-6-bromo-tetrahydro-pyran-3-yl ester 在 甲醇 、 三氟化硼乙醚 、 水 、 silver carbonate 、 zinc(II) chloride 、 锌 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 67.17h， 生成 4′-demethylepipodophyllotoxin 9-O-(2''-deoxy-2''-azido-4'',6''-di-O-(thiophen-2-ylidene)-β-D-glucopyranoside)
  参考文献：
  名称：

  Discovery of 4,6-O-Thenylidene-β-d-glucopyranoside-(2″-acetamido, 3″-acetyl-di-S-5-fluorobenzothizole/5-fluorobenzoxazole)-4′-demethylepipodophyllotoxin as Potential Less Toxic Antitumor Candidate Drugs by Reducing DNA Damage and Less Inhibition of PI3K

  摘要：

  As an FDA-approved drug, teniposide, was utilized in cancer treatment but was accompanied by a strong side effect in long-term clinical trials. This work discovered potential candidate drugs with low toxicity by modifying the molecule structure of teniposide through a structure-guided drug design approach. The IC50 value of novel 4,6-O-thenylidene-beta-D-glucopyranoside-(2 ''-acetamido, 3 ''-acetyl-di-S-5-fluorobenzothizole/5-fluorobenzoxazole)-4'-demethylepipodophyllotoxin (compounds 15 and 16) was 120.4-125.1 mu M, which was significantly improved by around 10 times more than teniposide (11.5-22.3 mu M) against healthy human cells (i.e., HL-7702, H8, MRC-5, and HMEC). In vivo studies demonstrated compounds 15 and 16 significantly suppressed the tumor growth in the HepG2 cell xenograft model without exhibiting obvious toxicity (LD50 values of 208.45 and 167.52 mg/kg), which was lower than that of teniposide (LD50 = 46.12 mg/kg). Compounds 15 and 16 caused mild gamma H2AX phosphorylation for low DNA toxicity and less inhibition of PI3K/Akt. Compounds 15 and 16 might be potential antitumor drugs with low toxicity.

  DOI：

  10.1021/acs.jmedchem.9b01354
• 作为产物：
  描述：

  2-azido-2-deoxy-D-glucose 在 溴化钛(IV) 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 Acetic acid (2R,3S,4R,5R,6R)-4-acetoxy-2-acetoxymethyl-5-azido-6-bromo-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  天然新蝶呤苷的高效全合成：新蝶呤葡萄糖苷和硫磷蝶呤

  摘要：

  1',2'-二-O-乙酰基-N2-(N,N-二甲基氨基亚甲基)-3-[2-(4-硝基苯基)乙基]新蝶呤(11a)及其1',2'-二-O-苯甲酰类似物 (11b) 分别由新蝶呤分 5 步制备。在三氟甲磺酸银存在下，用 2,3,4-三-O-苯甲酰基-D-吡喃葡萄糖基糖醛酸甲酯溴化物 (15b) 对 11a 进行糖基化，得到相应的 3'-O-(-D-吡喃葡萄糖基)新蝶呤衍生物 (18) 64% 的收率。用 2-叠氮基-3,4,6-三-O-苯甲酰基-2-脱氧-α-D-吡喃葡萄糖基溴 (21b) 对 11b 进行类似处理，得到相应的 3'-O-(-D-吡喃葡萄糖基)新蝶呤58% 产率的衍生物 (23a)。新蝶呤葡糖苷酸 (5) 和硫磷蝶呤 (6) 的首次合成是通过分别连续去除 18 和 23a 的保护基来实现的。引言 蝶啶环的 C-6 侧链上连接有各种糖的蝶啶苷被发现是由某些原核生物如蓝细菌和厌氧光合细菌产生的。1

  DOI：

  10.3987/com-16-s(s)32

文献信息

• Oligosaccharide glycosides having mammalian immunosuppresive and
  申请人：Glycomed Incorporated

  公开号：US05874411A1

  公开（公告）日：1999-02-23

  Disclosed are novel oligosaccharide glycosides having mammalian immunosuppressive and tolerogenic properties, pharmaceutical compositions containing such oligosaccharide glycosides and to methods of using such oligosaccharide glycosides to modulate cell-mediated immune responses in a mammal.

  揭示了具有哺乳动物免疫抑制和耐受性特性的新型寡糖糖苷，包含这种寡糖糖苷的药物组合物以及使用这种寡糖糖苷调节哺乳动物细胞介导免疫应答的方法。
• Nucleoside triphosphate mimicry: a sugar triazolyl nucleoside as an ATP-competitive inhibitor of B. anthracis pantothenate kinase
  作者：Andrew S. Rowan、Nathan I. Nicely、Nicola Cochrane、Wjatschesslaw A. Wlassoff、Al Claiborne、Chris J. Hamilton

  DOI：10.1039/b909729e

  日期：——

  The synthesis of a library of nucleoside triphoshate mimetics is described where the Mg2+ chelated triphosphate sidechain is replaced by an uncharged methylene-triazole linked monosaccharide sidechain. The compounds have been evaluated as inhibitors of Bacillus anthracispantothenate kinase and a competitive inhibitor has been identified with a Ki that is 3-fold lower than the Km value of ATP.

  本文描述了一组核苷三磷酸类似物的合成，其中以中性的甲撑-三唑连接的单糖侧链取代了与Mg2+螯合的核苷三磷酸侧链。这些化合物被评估为炭疽杆菌泛酸激酶的抑制剂，并且发现一种竞争性抑制剂的Ki值比ATP的Km值低3倍。
• Synthesis of <i>S</i>-Linked Glycopeptides in Aqueous Solution
  作者：Xiangming Zhu、Kandasamy Pachamuthu、Richard R. Schmidt

  DOI：10.1021/jo034148n

  日期：2003.7.1

  the peptide moiety, mixtures of DMF and water could be employed for successfully carrying out this reaction. Thus, S-glycosylated tripeptides 42-45 could be obtained. Combination of this method with chemical ligation was also successfully carried out.

  在碳酸钠作为碱存在下，在两相条件下，用O-乙酰基保护的糖基卤化物对高半胱氨酸和含半胱氨酸的肽进行直接S-糖基化的研究取得了优异的结果。因此，分别从葡糖基溴化物，半乳糖基溴化物，乳糖基溴化物，唾液酸氯和N-Troc保护的2-氨基-2-脱氧葡糖基溴化物S-糖基化的二肽分别为15、18-21、23、24和26-29。以优异的产量获得。或者，取决于肽部分的溶解度，可以使用DMF和水的混合物来成功地进行该反应。因此，可以获得S-糖基化的三肽42-45。该方法与化学连接的结合也已成功进行。
• Cyclic peptide antifungal agents
  申请人：Eli Lilly and Company

  公开号：US06323176B1

  公开（公告）日：2001-11-27

  The present invention relates to compounds of formula where R5 is a sugar moiety. The compounds are useful in inhibiting fungal and parasitic activity and infections.

  本发明涉及公式中R5为糖基团的化合物。这些化合物对抑制真菌和寄生虫活性以及感染具有用处。
• One-pot synthesis of a pentasaccharide with antibiotic activity against Helicobacter pylori
  作者：Ping Wang、Heeseob Lee、Minoru Fukuda、Peter H. Seeberger

  DOI：10.1039/b618662a

  日期：——

  A pentasaccharide that contains the alpha-1,4-GlcNAc mucin core two-branched O-glycan has been synthesized by a one-pot, two-step glycosylation strategy; this particular carbohydrate motif may provide protection against H. pylonri induced pathologies since the synthetic pentasaccharide inhibits cholesterol alpha-glucosyltransferase (IC50 of 0.47 mM).

  已经通过一锅两步糖基化策略合成了含有α-1,4-GlcNAc粘蛋白核心两支O聚糖的五糖。由于合成的五糖会抑制胆固醇α-葡萄糖基转移酶（IC50为0.47 mM），因此这种特殊的碳水化合物基序可提供针对幽门螺杆菌诱导的病理的保护作用。