(2S,3R,4E)-2-hexadecanamido-3-hydroxyoctadec-4-en-1-yl α-galactopyranosyl-(1→4)-β-galactopyranosyl-(1→4)-β-glucopyranoside | 69283-33-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 鞘脂
• 英文名称: (2S,3R,4E)-2-hexadecanamido-3-hydroxyoctadec-4-en-1-yl α-galactopyranosyl-(1→4)-β-galactopyranosyl-(1→4)-β-glucopyranoside
• 英文别名: alpha-D-Gal-(1->4)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1')-Cer(d18:1/18:0)；N-[(E,2S,3R)-1-[(2R,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-hydroxyoctadec-4-en-2-yl]octadecanamide
• CAS: 69283-33-6
• 化学式: C₅₄H₁₀₁NO₁₈
• 分子量: 1052.39
• InChiKey: KWGVNZWSEWAOMI-DHCJWVHISA-N

物化性质

• 沸点：
  1132.1±65.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿:甲醇(2:1)：可溶； DMSO：可溶；甲醇：温热的

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  73
• 可旋转键数：
  41
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  307
• 氢给体数：
  12
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  2,3,6,2',3',4',6'-hepta-O-acetyl-α-D-lactosyl trichloroacetimidate 在 盐酸 、 Hoveyda-Grubbs catalyst second generation 、 L-1,4-二硫代苏糖醇 、 sodium methylate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 manganese(ll) chloride 、 zinc dibromide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 53.5h， 生成 (2S,3R,4E)-2-hexadecanamido-3-hydroxyoctadec-4-en-1-yl α-galactopyranosyl-(1→4)-β-galactopyranosyl-(1→4)-β-glucopyranoside
  参考文献：
  名称：

  鞘糖脂及相关衍生物化学酶促合成的多样性导向策略

  摘要：

  开发了一种以多样性为导向的策略，将酶促聚糖组装和通过化学选择性交叉复分解和N-酰化的现场脂质重塑相结合，用于从常见的简单糖苷开始的鞘糖脂 (GSL) 合成。该策略通过一系列天然 GSL 和 GSL 衍生物进行了验证，并显示出几个优点。最值得注意的是，它实现了聚糖和脂质的双向多样化，包括引入设计的分子标签，以提供对生物学研究和应用有用的功能化 GSL。

  DOI：

  10.1021/acs.orglett.0c02847

文献信息

• Total synthesis of globotriaosylceramide (Gb3) and lysoglobotriaosylceramide (lysoGb3)
  作者：Kyriacos C. Nicolaou、Thomas J. Caulfield、Hideaki Katoaka

  DOI：10.1016/0008-6215(90)84079-a

  日期：1990.7

  achieved by stereocontrolled coupling of 2,3,4,6-tetra-O-benzyl-alpha-D-galactosyl fluoride (15) with phenyl O-(6-O-benzoyl-2,3-di-O-pivaloyl-beta-D-galactopyranosyl)- (1----4)-2,3,6-tri-O-pivaloyl-1-thio-beta-D-glucopyranoside (14) to form the P kappa antigen trisaccharide masked as a phenyl 1-thioglycoside at the reducing end. Thioglycoside 16 was converted into glycosyl fluoride 19, which was coupled

  我们最近报道了光学纯形式的球果糖神经酰胺（Gb3，1）的高效和立体控制合成。我们合成策略的关键是实现糖苷键形成的糖苷的两步活化以及（2S，3S，4E）-2-叠氮基-3-O-（叔丁基二甲基甲硅烷基）-4-的利用octadecen-1,3-di ol（9）作为鞘氨醇的当量。Gb3（1）和lysoGb3（2）的合成是通过将2,3,4,6-四-O-苄基-α-D-半乳糖基氟化物（15）与苯基O-（6-O-苯甲酰基-2,3-二-O-新戊酰基-β-D-吡喃半乳糖基）-（1 ---- 4）-2,3,6-三-O-新戊酰基-1-硫代-β-D-吡喃葡萄糖苷（ 14）形成在还原端被掩蔽为苯基1-硫代糖苷的Pκ抗原三糖。硫代糖苷16转化为糖基氟化物19，与高产量的9配对。偶联产物20分别通过四步和三步转化为标题化合物1和2。本文以完整的实验详细介绍了1和2的总合成。
• A practical and enantioselective synthesis of glycosphingolipids and related compounds. Total synthesis of globotriaosylceramide (Gb3)
  作者：K. C. Nicolaou、T. Caulfield、H. Kataoka、T. Kumazawa

  DOI：10.1021/ja00231a071

  日期：1988.11
• Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease
  作者：Satoshi Ishii、Atsumi Taguchi、Nozomu Okino、Makoto Ito、Hiroki Maruyama

  DOI：10.1074/jbc.ra120.012665

  日期：2020.4

  Fabry disease is a heritable lipid disorder caused by the low activity of ?-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(?2) containing the lyso-Gb3(?2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(?2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease.
• “Armed-disarmed” glycosidation strategy based on glycosyl donors and acceptors carrying phosphoroamidate as a leaving group: A convergent synthesis of globotriaosylceramide
  作者：Shun-ichi Hashimoto、Hiroki Sakamoto、Takeshi Honda、Hiroshi Abe、Sei-ichi Nakamura、Shiro Ikegami

  DOI：10.1016/s0040-4039(97)10365-3

  日期：1997.12

  A stereocontrolled synthesis of globotriaosylcernmide with three different glycosidic linkages has been accomplished by linear and convergent routes exploiting "armed-disarmed" glycosidation methodology bared on glycosyl donors and accepters carrying tetramethylphosphoroamidate as a leaving group. In particular, the convergent strategy featuring a coupling of a galactosyl-(1-->4)-galactosyl donor with a glucosylceramide derivative has proven to be extremely efficient. (C) 1997 Elsevier Science Ltd.
• A Diversity-Oriented Strategy for Chemoenzymatic Synthesis of Glycosphingolipids and Related Derivatives
  作者：Qingjiang Li、Mohit Jaiswal、Rajendra S. Rohokale、Zhongwu Guo

  DOI：10.1021/acs.orglett.0c02847

  日期：2020.11.6

  glycan assembly and on-site lipid remodeling via chemoselective cross-metathesis and N-acylation was developed for glycosphingolipid (GSL) synthesis starting from a common, simple glycoside. The strategy was verified with a series of natural GSLs and GSL derivatives and showed several advantages. Most notably, it enabled two-way diversification of the glycan and lipid, including introduction of designed

  开发了一种以多样性为导向的策略，将酶促聚糖组装和通过化学选择性交叉复分解和N-酰化的现场脂质重塑相结合，用于从常见的简单糖苷开始的鞘糖脂 (GSL) 合成。该策略通过一系列天然 GSL 和 GSL 衍生物进行了验证，并显示出几个优点。最值得注意的是，它实现了聚糖和脂质的双向多样化，包括引入设计的分子标签，以提供对生物学研究和应用有用的功能化 GSL。