(1R,2S,3S,4S,5S,6S)-2-((S)-2-amino-2-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)ethylamino)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)cyclohexanol | 1319731-16-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,2S,3S,4S,5S,6S)-2-((S)-2-amino-2-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)ethylamino)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)cyclohexanol
• CAS: 1319731-16-2
• 化学式: C₅₆H₈₀N₂O₇
• 分子量: 893.26
• InChiKey: FGCZBLUCJJOJOD-YMGNTMMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.85
• 重原子数：
  65.0
• 可旋转键数：
  30.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  113.66
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,4S,5S,6S)-2-((S)-2-amino-2-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)ethylamino)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)cyclohexanol 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 20.0~25.0 ℃ 、202.66 kPa 条件下， 反应 48.0h， 生成 N-((S)-1-((1S,2R)-1,2-dihydroxyhexadecyl)-2-((1S,2S,3S,4S,5S,6R)-2,3,4,6-tetrahydroxy-5-hydroxymethylcyclohexylamino)ethyl)cerotamide hydrochloride
  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：

  (1R,2R,3S,4S,5R,6R)-2,3,4-tris(benzyloxy)-5-((benzyloxy)methyl )-7-oxabicyclo[4.1.0]heptane 在 lithium aluminium tetrahydride 、 sodium azide 、 lithium perchlorate 、 caesium carbonate 、 苯硫酚 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 42.0h， 生成 (1R,2S,3S,4S,5S,6S)-2-((S)-2-amino-2-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)ethylamino)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)cyclohexanol
  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