(1R,2R,3S,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)cyclohexane-1,2-diol | 1319731-27-5

• 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: (1R,2R,3S,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)cyclohexane-1,2-diol
• 英文别名: (1R,2R,3S,4S,5S,6S)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)cyclohexane-1,2-diol
• CAS: 1319731-27-5
• 化学式: C₃₅H₃₈O₆
• 分子量: 554.683
• InChiKey: BMUNZTHUYXJOBX-RDWYLJQVSA-N

物化性质

• 沸点：
  670.9±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)cyclohexane-1,2-diol 、 2-乙酰氧基异丁酰溴 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Galacto-Configured Aminocyclitol Phytoceramides Are Potent in Vivo Invariant Natural Killer T Cell Stimulators

  摘要：

  A new class of a-galactosylceramide (alpha GC) nonglycosidic analogues bearing galacto-configured aminocyclitols as sugar surrogates have been obtained. The aminocyclohexane having a hydroxyl substitution pattern similar to an a-galactoside is efficiently obtained by a sequence involving Evans aldol reaction and ring-closing metathesis with a Grubbs catalyst to give a key intermediate cyclohexene, which has been converted in galacto-aminocyclohexanes that are linked through a secondary amine to a phytoceramide lipid having a cerotyl N-acyl group. Natural Killer T (NKT) cellular assays have resulted in the identification of an active compound, HS161, which has been found to promote NKT cell expansion in vitro in a similar fashion but more weakly than alpha GC. This compound stimulates the release of Interferon-gamma (IFN gamma) and Interleukin-4 (IL-4) in iNKT cell culture but with lower potency than alpha GC. The activation of Invariant Natural Killer T (iNKT) cells by this compound has been confirmed in flow cytometry experiments. Remarkably, when tested in mice, HS161 selectively induces a very strong production of IFN-gamma indicative of a potent Th1 cytokine profile. Overall, these data confirm the agonist activity of alpha GC lipid analogues having charged amino-substituted polar heads and their capacity to modulate the response arising from iNKT cell activation in vivo.

  DOI：

  10.1021/ja202610x
• 作为产物：
  描述：

  (S)-3-((2R,3S,4S,5S)-4,5-bis(benzyloxy)-3-hydroxy-2-vinylhept-6-enoyl)-4-isopropyloxazolidin-2-one 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 四氧化锇 、 锂硼氢 、 水 、 sodium hydride 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 、 叔丁醇 为溶剂， 反应 52.0h， 生成 (1R,2R,3S,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)cyclohexane-1,2-diol
  参考文献：
  名称：

  Galacto-Configured Aminocyclitol Phytoceramides Are Potent in Vivo Invariant Natural Killer T Cell Stimulators

  摘要：

  A new class of a-galactosylceramide (alpha GC) nonglycosidic analogues bearing galacto-configured aminocyclitols as sugar surrogates have been obtained. The aminocyclohexane having a hydroxyl substitution pattern similar to an a-galactoside is efficiently obtained by a sequence involving Evans aldol reaction and ring-closing metathesis with a Grubbs catalyst to give a key intermediate cyclohexene, which has been converted in galacto-aminocyclohexanes that are linked through a secondary amine to a phytoceramide lipid having a cerotyl N-acyl group. Natural Killer T (NKT) cellular assays have resulted in the identification of an active compound, HS161, which has been found to promote NKT cell expansion in vitro in a similar fashion but more weakly than alpha GC. This compound stimulates the release of Interferon-gamma (IFN gamma) and Interleukin-4 (IL-4) in iNKT cell culture but with lower potency than alpha GC. The activation of Invariant Natural Killer T (iNKT) cells by this compound has been confirmed in flow cytometry experiments. Remarkably, when tested in mice, HS161 selectively induces a very strong production of IFN-gamma indicative of a potent Th1 cytokine profile. Overall, these data confirm the agonist activity of alpha GC lipid analogues having charged amino-substituted polar heads and their capacity to modulate the response arising from iNKT cell activation in vivo.

  DOI：

  10.1021/ja202610x

文献信息

• [EN] PHARMACOLOGICAL CHAPERONES FOR ENZYME TREATMENT THERAPY<br/>[FR] CHAPERONS PHARMACOLOGIQUES POUR UNE THÉRAPIE PAR TRAITEMENT ENZYMATIQUE
  申请人：UNIV LEIDEN

  公开号：WO2020046132A1

  公开（公告）日：2020-03-05

  The present invention relates to therapeutic methods for the management of a patient's lysosomal storage disease by enzyme replacement therapy. The methods involve the use of combinations of, and kits containing: a) an exogenous lysosomal hydrolaseor an endogenous produced natural mutant glycosidase by (multi)gene therapy, and b) a reversible cyclophellitol-derived glycosidase inhibitor comprising a cyclic sulfamidate functional groupattached to a cyclohexene ring, capable of competitively blocking the active site of the lysosomal hydrolase.

  本发明涉及通过酶替代疗法治疗患者溶酶体贮积病的治疗方法。该方法涉及使用以下组合和装置：a）外源性溶酶体水解酶或通过（多）基因治疗产生的内源性天然突变的糖苷酶，以及b）可逆的环磷酸内酰胺衍生的糖苷酶抑制剂，其包含连接到环己烯环上的环磺酰胺基团，能够竞争性地阻塞溶酶体水解酶的活性位点。