N-((S)-1-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)-2-((1S,2S,3S,4S,5R)-2,3,4-tris(benzyloxy)-5-(benzyloxymethyl)cyclohexylamino)ethyl)-2-nitrobenzenesulfonamide | 1319731-13-9

• 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: N-((S)-1-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)-2-((1S,2S,3S,4S,5R)-2,3,4-tris(benzyloxy)-5-(benzyloxymethyl)cyclohexylamino)ethyl)-2-nitrobenzenesulfonamide
• CAS: 1319731-13-9
• 化学式: C₆₂H₈₃N₃O₁₀S
• 分子量: 1062.42
• InChiKey: WAIRVFCVOMENFO-YHLDAFJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.8
• 重原子数：
  76.0
• 可旋转键数：
  34.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  156.72
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-((S)-1-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)-2-((1S,2S,3S,4S,5R)-2,3,4-tris(benzyloxy)-5-(benzyloxymethyl)cyclohexylamino)ethyl)-2-nitrobenzenesulfonamide 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 caesium carbonate 、 苯硫酚 、 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 、 乙腈 为溶剂， 20.0~25.0 ℃ 、202.66 kPa 条件下， 反应 72.0h， 生成 N-((S)-1-((1S,2R)-1,2-dihydroxyhexadecyl)-2-((1S,2S,3S,4S,5R)-2,3,4-trihydroxy-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：

  (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) 、 lithium aluminium tetrahydride 、 锂硼氢 、 sodium azide 、 硼烷四氢呋喃络合物 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 48.0h， 生成 N-((S)-1-((4S,5R)-2,2-dimethyl-5-tetradecyl-1,3-dioxolan-4-yl)-2-((1S,2S,3S,4S,5R)-2,3,4-tris(benzyloxy)-5-(benzyloxymethyl)cyclohexylamino)ethyl)-2-nitrobenzenesulfonamide
  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