3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide | 186419-71-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide
• 英文别名: (2R,3R,4S,5R,6R)-2-bromo-3-fluoro-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxane
• CAS: 186419-71-6
• 化学式: C₂₇H₂₈BrFO₄
• 分子量: 515.419
• InChiKey: FKASUEIUZFTGIZ-ACFIUOAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide 在 10% Pt/activated carbon 、 palladium 10% on activated carbon sodium azide 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 22.33h， 生成 N-(3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl)-2-aminoacetamide
  参考文献：
  名称：

  Conjugates of 2-fluoro-2-deoxy-glucose and their uses as anti cancer agents

  摘要：

  本发明涉及一般式（I）的化合物：其中：- R1、R2和R3分别独立地表示氢原子或可选择取代的较低烷基，（C1-C7）酰基团或苄基，- R4是可选择取代和/或中断的碳氢链，- X和Y分别独立地从-NH-，-NR'-，-CO-，-NH（CO）-，-NH（CO）NH-，-NR'（CO）-，-O（CO）NH-，-O（CO）NR'-，-（CO）NH-，-（CO）NR'-，-NH（CO）（R"）NH（CO）-，-（CO）NH（R"（CO）NH-，-O-，-（CO）O-，-NH（CO）O-，-SC（O）NH-，-NHSO2-，-NR'SO2-和-O（CO）-中选择，并且最好彼此不同，其中R'是可选择取代的较低烷基团，R"是（C1-C3）烷基，- Z基团代表抗肿瘤剂，- n表示0或1，- 及其药用盐。还涉及将这些化合物用作抗癌剂。

  公开号：

  EP1881000A1
• 作为产物：
  描述：

  3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide 在 氢氧化钾 、 溴 、 sodium acetate 、 氢化钾 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 16.67h， 生成 3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide
  参考文献：
  名称：

  Design and Synthesis of 2‘-Deoxy-2‘-Fluorodisaccharides as Mechanism-Based Glycosidase Inhibitors That Exploit Aglycon Specificity

  摘要：

  Stable, aglycon-specific inactivators of glycosidases have considerable potential as fools in the study of mechanisms of oligosaccharide processing, and possibly as avenues toward new therapeutics. Glycosidases for which the rate-determining step with the natural substrate is the hydrolysis of the glycosyl-enzyme intermediate are shown to be inactivated by the 2'-deoxy-2'-fluoro derivative of this substrate. Thus Agrobacterium faecalis beta-glucosidase is inactivated by 2'-deoxy-2'-fluorocellobiose according to inactivation parameters of k(i) = 0.018 min(-1) and K-i = 20 mM. Inactivation is shown to occur via the accumulation of the same 2-deoxy-2-fluoroglycosyl-enzyme intermediate as that formed using activated 2-deoxy-2-fluoroglycosides by identification of the labeled peptide in proteolytic digests. Thus, interactions between the enzyme and the sugar aglycon provide sufficient transition state stabilization to allow formation and trapping of the glycosyl-enzyme. beta-Glucocerebrosidase, a beta-glucosidase specific for hydrolysis of glucocerebrosides, is not inactivated by 2'-deoxy-2'-fluorocellobiose, thereby demonstrating the aglycon specificity of this class of inactivator.

  DOI：

  10.1021/ja9627454

文献信息

• Diastereoselective sp³ C–O Bond Formation via Visible Light-Induced, Copper-Catalyzed Cross-Couplings of Glycosyl Bromides with Aliphatic Alcohols
  作者：Fei Yu、Jalen L. Dickson、Ravi S. Loka、Hengfu Xu、Richard N. Schaugaard、H. Bernhard Schlegel、Long Luo、Hien M. Nguyen

  DOI：10.1021/acscatal.0c01470

  日期：2020.6.5

  electrophiles to control α-1,2-cis selectivity. In our approach, earth-abundant copper not only acts as a photocatalyst and a bond-forming catalyst, but also enforces the stereocontrolled formation of anomeric C–O bonds. This cross-coupling protocol enables highly diastereoselective access to a wide variety of α-1,2-cis-glycosides and biologically relevant α-glycan oligosaccharides. Our work provides a foundation

  铜催化的交叉偶联反应已成为产生碳-杂原子键（许多有机分子的重要框架）的最有效方法之一。但是，由于铜的氧化加成反应迟钝，铜催化的卤代烷与烷基醇的C（sp 3）–O交叉偶联仍然难以实现。为解决这一挑战，我们开发了一种催化铜系统，该系统可借助可见光克服铜的氧化加成障碍，并有效地促进糖基溴化物与脂肪族醇的交叉偶联，从而提供具有C（sp 3）-O键的高非对映选择性。重要的是，该催化体系导致温和而有效的立体选择性构建α-1,2-顺式的方法苷，这是最重要的，但具有挑战性。通常，α-1,2-顺式糖苷C–O键形成过程中的立体化学结果是无法预测的，并且取决于与碳水化合物偶联伙伴结合的保护基的空间和电子性质。当前，最可靠的方法依赖于在碳水化合物亲电体的C2和C4位置使用手性辅助或氢键引导基团来控制α-1,2-顺式选择性。在我们的方法中，富含地球的铜不仅充当光催化剂和形成键的催化剂，而且还增强了异头C-O键的立体
• Phenanthroline‐Catalyzed Stereoretentive Glycosylations
  作者：Fei Yu、Jiayi Li、Paul M. DeMent、Yi‐Jung Tu、H. Bernhard Schlegel、Hien M. Nguyen

  DOI：10.1002/anie.201901346

  日期：2019.5.20

  limitations in synthetic access to well-defined oligosaccharides. Most of the current methods rely on the design of specialized coupling partners to control selectivity during the formation of glycosidic bonds. Reported herein is the use of a commercially available phenanthroline to catalyze stereoretentive glycosylation with glycosyl bromides. The method provides efficient access to α-1,2-cis glycosides. This

  碳水化合物是自然界中许多生物活性分子的基本组成部分。然而，阐明其作用方式的努力往往受到合成获得明确寡糖的限制的阻碍。大多数当前方法依赖于设计专门的偶联配偶体来控制糖苷键形成过程中的选择性。本文报道了使用可商购的菲咯啉来催化与糖基溴的立体保留糖基化。该方法提供了对 α-1,2-cis 糖苷的有效获取。该协议已用于八糖佐剂的大规模合成。密度泛函理论计算以及动力学研究表明，该反应通过双 SN 2 机制进行。
• Synthesis and cytotoxic properties of new fluorodeoxyglucose-coupled chlorambucil derivatives
  作者：Bastien Reux、Valérie Weber、Marie-Josephe Galmier、Michèle Borel、Michel Madesclaire、Jean-Claude Madelmont、Eric Debiton、Pascal Coudert

  DOI：10.1016/j.bmc.2008.03.038

  日期：2008.5

  Frequently used in the treatment of malignant cells, alkylating agents, like most anticancer substances, produce adverse side effects caused by the toxicity of the agents toward normal tissues and lose efficiency through poor distribution to target sites. Our approach to developing more selective drugs with low systemic toxicity is based on the premise that the body distribution and cell uptake of a drug can be altered by attaching a neoplastic cell-specific uptake enhancer, such as 2-fluoro-2-deoxyglucose (FDG), the radiotracer most frequently used in PET for tumor imaging. Two properties of deoxyglucose, namely preferential accumulation in neoplastic cells and inhibition of glycolysis, underpin this targeting approach. Here, we report the synthesis of 19 new chlorambucil glycoconjugates in which the alkylating drug is attached to the C-1 position of FDG, directly or via different linkages. This set of compounds was evaluated for in vitro cytotoxicity against different human normal and tumor cell lines. There was a significant improvement in the in vitro cytotoxicity of peracetylated glucoconjugates compared with the free substance. Four compounds were finally selected for further in vivo studies owing to their lack of oxidative stress-inducing properties. (c) 2008 Elsevier Ltd. All rights reserved.
• Design and Synthesis of 2‘-Deoxy-2‘-Fluorodisaccharides as Mechanism-Based Glycosidase Inhibitors That Exploit Aglycon Specificity
  作者：John D. McCarter、Wai Yeung、Jack Chow、David Dolphin、Stephen G. Withers

  DOI：10.1021/ja9627454

  日期：1997.6.1

  Stable, aglycon-specific inactivators of glycosidases have considerable potential as fools in the study of mechanisms of oligosaccharide processing, and possibly as avenues toward new therapeutics. Glycosidases for which the rate-determining step with the natural substrate is the hydrolysis of the glycosyl-enzyme intermediate are shown to be inactivated by the 2'-deoxy-2'-fluoro derivative of this substrate. Thus Agrobacterium faecalis beta-glucosidase is inactivated by 2'-deoxy-2'-fluorocellobiose according to inactivation parameters of k(i) = 0.018 min(-1) and K-i = 20 mM. Inactivation is shown to occur via the accumulation of the same 2-deoxy-2-fluoroglycosyl-enzyme intermediate as that formed using activated 2-deoxy-2-fluoroglycosides by identification of the labeled peptide in proteolytic digests. Thus, interactions between the enzyme and the sugar aglycon provide sufficient transition state stabilization to allow formation and trapping of the glycosyl-enzyme. beta-Glucocerebrosidase, a beta-glucosidase specific for hydrolysis of glucocerebrosides, is not inactivated by 2'-deoxy-2'-fluorocellobiose, thereby demonstrating the aglycon specificity of this class of inactivator.
• Conjugates of 2-fluoro-2-deoxy-glucose and their uses as anti cancer agents
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1881000A1

  公开（公告）日：2008-01-23

  The present invention relates to compounds of general formula (I): wherein: - R1, R2 and R3 mean, independently from the others, an hydrogen atom or an optionally substituted lower alkyl, a (C1-C7)acyl group or a benzyl, - R4 is an optionally substituted and/or interrupted hydrocarbon linker, - X and Y are selected independently from each other from the group consisting of -NH-, -NR'-, -CO-, -NH(CO)-, -NH(CO)NH-, -NR'(CO)-, -O(CO)NH-, -O(CO)NR'-, -(CO)NH-, -(CO)NR'-, -NH(CO)(R")NH(CO)-, -(CO)NH(R"(CO)NH-, -O-, -(CO)O-, -NH(CO)O-, -SC(O)NH-, -NHSO2-, -NR'SO2- and -O(CO)- and preferably are different one from the other, with R' being an optionally substituted lower alkyl group, and R" being a (C1-C3) alkylene, - Z moiety represents an anti-neoplasic agent, - n means 0 or 1, - and the pharmaceutically acceptable salts thereof. It relates also to the use of such compounds as anti cancer agents.

  本发明涉及一般式（I）的化合物：其中：- R1、R2和R3分别独立地表示氢原子或可选择取代的较低烷基，（C1-C7）酰基团或苄基，- R4是可选择取代和/或中断的碳氢链，- X和Y分别独立地从-NH-，-NR'-，-CO-，-NH（CO）-，-NH（CO）NH-，-NR'（CO）-，-O（CO）NH-，-O（CO）NR'-，-（CO）NH-，-（CO）NR'-，-NH（CO）（R"）NH（CO）-，-（CO）NH（R"（CO）NH-，-O-，-（CO）O-，-NH（CO）O-，-SC（O）NH-，-NHSO2-，-NR'SO2-和-O（CO）-中选择，并且最好彼此不同，其中R'是可选择取代的较低烷基团，R"是（C1-C3）烷基，- Z基团代表抗肿瘤剂，- n表示0或1，- 及其药用盐。还涉及将这些化合物用作抗癌剂。