2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyloxyl-4,6-O-benzyllidene-α-D-galactopyranosyl)-D-ribooctadecane-1,3,4-triol | 951767-71-8

• 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: 2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyloxyl-4,6-O-benzyllidene-α-D-galactopyranosyl)-D-ribooctadecane-1,3,4-triol
• 英文别名: (2S,4aS,6S,7R,8S,8aR)-6-(((2S,3S,4R)-2-azido-3,4-bis(benzyloxy)octadecyl)oxy)-7,8-bis(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxine；2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyl-4,6-O-benzylidene-α-D-galactopyranosyl)octadecane-1,3,4-triol；(2S,4aR,6S,7R,8S,8aS)-6-[(2S,3S,4R)-2-azido-3,4-bis(phenylmethoxy)octadecoxy]-2-phenyl-7,8-bis(phenylmethoxy)-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxine
• CAS: 951767-71-8
• 化学式: C₅₉H₇₅N₃O₈
• 分子量: 954.26
• InChiKey: JKHYRKPTODORRZ-CASPKDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.9
• 重原子数：
  70
• 可旋转键数：
  32
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  88.2
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyloxyl-4,6-O-benzyllidene-α-D-galactopyranosyl)-D-ribooctadecane-1,3,4-triol 在 三乙基硅烷 、 4-二甲氨基吡啶 、 三氟甲磺酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Introduction of aromatic group on 4′-OH of α-GalCer manipulated NKT cell cytokine production

  摘要：

  The glycosphingolipid alpha-GalCer has been found to influence mammalian immune system significantly through the natural killer T cells. Unfortunately, the pre-clinical and clinical studies revealed several critical disadvantages that prevented the therapeutic application of alpha-GalCer in treating cancer and other diseases. Recently, the detailed illustration of the CD1d/alpha-GalCer/NKT TCR complex crystal structural, together with other latest structural and biological understanding on glycolipid ligands and NKT cells, provided a new platform for developing novel glycolipid ligands with optimized therapeutic effects. Here, we designed a series of novel aromatic group substituted alpha-GalCer analogues. The biological activity of these analogues was characterized and the results showed the unique substitution group manipulated the immune responses of NKT cells. Computer modeling and simulation study indicated the analogues had unique binding mode when forming CD1d/glycolipid/NKT TCR complex, comparing to original alpha-GalCer. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.11.061
• 作为产物：
  描述：

  糖脂 在 copper(ll) sulfate pentahydrate 、 硫酸 、 triflic azide 、 silver trifluoromethanesulfonate 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 36.0h， 生成 2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyloxyl-4,6-O-benzyllidene-α-D-galactopyranosyl)-D-ribooctadecane-1,3,4-triol
  参考文献：
  名称：

  Synthesis and Th1-immunostimulatory activity of α-galactosylceramide analogues bearing a halogen-containing or selenium-containing acyl chain

  摘要：

  A novel series of CD1d ligand alpha-galactosylceramides (alpha-GalCers) were synthesized by incorporation of the heavy atoms Br and Se in the acyl chain backbone of alpha-galactosyl-N-cerotoylphytosphingosine. The synthetic analogues are potent CD1d ligands and stimulate mouse invariant natural killer T (iNKT) cells to selectively enhance Th1 cytokine production. These synthetic analogues would be efficient X-ray crystallographic probes to disclose precise atomic positions of alkyl carbons and lipid-protein interactions in KRN7000/CD1d complexes. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.06.007

文献信息

• Enhancing T cell responses and tumour immunity by vaccination with peptides conjugated to a weak NKT cell agonist
  作者：Benjamin J. Compton、Kathryn J. Farrand、Ching-wen Tang、Taryn L. Osmond、Mary Speir、Astrid Authier-Hall、Jing Wang、Peter M. Ferguson、Susanna T. S. Chan、Regan J. Anderson、Taylor R. Cooney、Colin M. Hayman、Geoffrey M. Williams、Margaret A Brimble、Collin R. Brooks、Lin-Kin Yong、Leonid S. Metelitsa、Dirk M. Zajonc、Dale I. Godfrey、Olivier Gasser、Robert Weinkove、Gavin F. Painter、Ian F. Hermans

  DOI：10.1039/c8ob02982b

  日期：——

  Through chemical synthesis we have designed out the toxicity associated with the powerful vaccine adjuvant α-GalCer.

  通过化学合成，我们成功设计出了与强效疫苗佐剂α-GalCer相关的毒性。
• A comparison of benzyl and 2-naphthylmethyl ethers as permanent hydroxyl protecting groups in the synthesis of α-galactoglycosphingolipids KRN7000 and PBS-57
  作者：Dongming Yao、Yichu Liu、Qi Gao、Qiang Sui、Xiaoping Liu、Ning Ding

  DOI：10.1080/07328303.2017.1375114

  日期：2017.6.13

  synthesis. Here we conducted the direct comparison of benzyl and 2-naphthylmethyl (Nap) ethers as permanent hydroxyl protecting groups for the synthesis of KRN7000, as well as the practical synthesis of a biologically active α-GalGSLs PBS-57. This work further revealed the advantages of Nap ether over benzyl ether for permanent hydroxyl protection in the synthesis of α-GalGSLs.

  图形摘要由于对海洋衍生的α-半乳糖鞘脂（α-GalGSL）的生物学特性的关注，许多工作都集中在其合成的开发上。在这里，我们进行了直接比较作为合成KRN7000的永久羟基保护基的苄基和2-萘基甲基（Nap）醚，以及对具有生物活性的α-GalGSLsPBS-57的实际合成。这项工作进一步揭示了在合成α-GalGSLs中，Nap醚优于苄基醚的永久羟基保护作用。
• Divergent synthetic approach to 6′′-modified α-GalCer analogues
  作者：Nora Pauwels、Sandrine Aspeslagh、Gerd Vanhoenacker、Koen Sandra、Esther D. Yu、Dirk M. Zajonc、Dirk Elewaut、Bruno Linclau、Serge Van Calenbergh

  DOI：10.1039/c1ob06235b

  日期：——

  A synthetic approach is presented for the synthesis of galacturonic acid and D-fucosyl modified KRN7000. The approach allows for late-stage functionalisation of both the sugar 6′′-OH and the sphingosine amino groups, which enables convenient synthesis of promising 6′′-modified KRN7000 analogues.

  提出了一种合成半乳糖醛酸和D-岩藻糖修饰的KRN7000的合成方法。该方法允许对糖的6′′-OH和神经氨酸氨基组进行后期功能化，从而便于合成有前景的6′′修饰的KRN7000类似物。
• Synthesis and structure-activity relationships of cerebroside analogues as substrates of cerebroside sulphotransferase and discovery of a competitive inhibitor
  作者：Wenjin Li、Joren Guillaume、Younis Baqi、Isabell Wachsmann、Volkmar Gieselmann、Serge Van Calenbergh、Christa E. Müller

  DOI：10.1080/14756366.2020.1791841

  日期：2020.1.1

  competitive CST inhibitors, we synthesised and investigated analogues of the substrate galactosylceramide with variations at the anomeric position, the acyl substituent and the carbohydrate moiety, and investigated their structure–activity relationships. While most of the compounds behaved as substrates, α-galactosylceramide 16 was identified as the first competitive CST inhibitor. Compound 16 can

  摘要 异色性白细胞营养不良（MLD）是一种罕见的遗传性疾病，其特征是芳基硫酸酯酶A酶功能异常，导致溶酶体积累脑苷脂硫酸盐（硫酸盐），导致患者随后发生脱髓鞘。半乳糖基神经酰胺（脑苷脂）磺基转移酶（CST）催化硫酸基团从3'-磷酸腺苷-5'-磷酸酯（PAPS）向脑苷脂的转移，产生硫化物。有人提出通过抑制CST对芳基硫酸酯酶A进行底物还原疗法是一种有前途的治疗方法。为了鉴定竞争性CST抑制剂，我们合成并研究了底物半乳糖基神经酰胺的类似物，其端基异构体位置，酰基取代基和碳水化合物部分均存在差异，并研究了它们的结构-活性关系。16被确定为第一种竞争性CST抑制剂。化合物16可以用作开发用于治疗这种破坏性疾病的药物MLD的新的先导结构，目前尚无小分子疗法。
• Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist
  作者：Xi-Feng Wang、Meng-Jia Zhang、Na He、Ya-Cong Wang、Cheng Yan、Xiang-Zhao Chen、Xiao-Fei Gao、Jun Guo、Rui Luo、Zheng Liu

  DOI：10.1021/acs.jmedchem.1c00881

  日期：2021.8.12