(E,2S,3R,4R,5S,14R)-2-氨基-3,4,5,14-四羟基二十碳-6-烯酸 | 121025-45-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (E,2S,3R,4R,5S,14R)-2-氨基-3,4,5,14-四羟基二十碳-6-烯酸
• 英文名称: sphingofungin B
• 英文别名: (E,2S,3R,4R,5S,14R)-2-amino-3,4,5,14-tetrahydroxyicos-6-enoic acid
• CAS: 121025-45-4
• 化学式: C₂₀H₃₉NO₆
• 分子量: 389.533
• InChiKey: UAPFYKYEEDCCTL-MXSQXUFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  27
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  144
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1H-吡唑-1-甲脒盐酸盐 、 (E,2S,3R,4R,5S,14R)-2-氨基-3,4,5,14-四羟基二十碳-6-烯酸 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以90%的产率得到sphingofungin A
  参考文献：
  名称：

  抗真菌鞘氨醇家族的模块化方法：鞘氨醇 A 和 C 的简明全合成

  摘要：

  通过结合多功能脱羧偶联反应和交叉复分解方案，开发了抗真菌和抗寄生虫鞘氨醇 A-D 及其同系物的简短而灵活的全合成。

  DOI：

  10.1002/anie.202112616
• 作为产物：
  描述：

  在 盐酸 、 三氯化硼 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 50.5h， 生成 (E,2S,3R,4R,5S,14R)-2-氨基-3,4,5,14-四羟基二十碳-6-烯酸
  参考文献：
  名称：

  抗真菌鞘氨醇家族的模块化方法：鞘氨醇 A 和 C 的简明全合成

  摘要：

  通过结合多功能脱羧偶联反应和交叉复分解方案，开发了抗真菌和抗寄生虫鞘氨醇 A-D 及其同系物的简短而灵活的全合成。

  DOI：

  10.1002/anie.202112616

文献信息

• Use of heterocycles as chiral ligands and auxiliaries in asymmetric syntheses of sphingosine, sphingofungins B and F
  作者：Shū Kobayashi、Takayuki Furuta

  DOI：10.1016/s0040-4020(98)00484-0

  日期：1998.8

  prepared from 5 according to standard transformation. The chiral hydrophobic side chain (6) of sphingofungin B was synthesized using a catalytic asymmetric aldol reaction using chiral ligand 1-ent. Another key step in the total synthesis of sphingofungin B was a condensation of chiral aldehyde 7 and chiral heterocycle 2. Similarly, the reaction of chiral aldehyde 8 with heterocycle 3 was a key step for

  D-赤型-鞘氨醇及其衍生物（二氢鞘氨醇，顺式鞘氨醇等），鞘氨醇B和F已经由简单的非手性化合物合成，使用杂环化合物作为关键的手性配体和助剂。5-苯甲氧基-4-乙炔基-2,2-二甲基-1,3-二恶烷（5位或5位）是合成鞘氨醇家族的关键中间体，是由1-三甲基甲硅烷基丙酸和乙烯酮甲硅烷基乙缩醛4制备的。 Sn（OTf）2-手性配体1或1-ent催化的不对称羟醛反应。鞘氨醇及其衍生物易于根据标准转化由5制备。手性疏水侧链（6）的鞘芬净B是通过手性配体1-ent催化的不对称醛缩反应合成的。全合成鞘氨醇单丁酯B的另一个关键步骤是手性醛7和手性杂环2的缩合。同样，手性醛8与杂环3的反应是合成鞘氨醇单胞菌F的关键步骤。在两种情况下，高度非对映选择性反应均能顺利进行，从而以高收率提供了相应的加合物。
• Catalytic Asymmetric Syntheses of Antifungal Sphingofungins and Their Biological Activity as Potent Inhibitors of Serine Palmitoyltransferase (SPT)
  作者：Shū Kobayashi、Takayuki Furuta、Takaomi Hayashi、Masahiro Nishijima、Kentaro Hanada

  DOI：10.1021/ja9730829

  日期：1998.2.1

  Unambiguous synthetic routes to sphingofungins B and F and to their stereoisomers have been developed based on the tin(II)-catalyzed asymmetric aldol reaction (Chiral Lewis Acid-Controlled Synthesis (CLAC Synthesis)). Efficient enantioselective synthesis using a catalytic amount of a chiral source as well as the effectiveness of this strategy for the synthesis of the sphingofungin family have been successfully

  基于锡 (II) 催化的不对称醛醇反应（手性路易斯酸控制合成（CLAC 合成）），已经开发了鞘氨醇 B 和 F 及其立体异构体的明确合成路线。使用催化量的手性源进行有效的对映选择性合成以及该策略在合成鞘氨醇家族中的有效性已被成功证明。使用合成的鞘氨醇 B 的立体异构体，揭示了其立体化学与其 SPT 抑制活性的相关性。
• Chirality extension of an oxazine building block en route to total syntheses of (+)-hyacinthacine A₂ and sphingofungin B
  作者：Seok-Hwi Park、Xiangdan Jin、Jong-Cheol Kang、Changyoung Jung、Seong-Soo Kim、Sung-Soo Kim、Kee-Young Lee、Won-Hun Ham

  DOI：10.1039/c5ob00251f

  日期：——

  achieved via a diastereomerically enriched oxazine intermediate. The key strategies include palladium(0)-catalyzed intramolecular oxazine formation and diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was synthesized in 13 steps and 10.2% overall yield and the synthesis of sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall yield from (R)-methyl

  通过非对映异构体富集的恶嗪中间体可实现立体式控制的（+）-扁豆碱A 2和神经鞘氨醇B的合成。关键策略包括钯（0）催化的分子内恶嗪形成和向醛的非对映选择性亲核加成。（+）-Hyacinthacine A 2的合成步骤为13个步骤，总产率为10.2％，鞘氨醇单糖B的合成以线性顺序进行，历时15个步骤，从（R）-甲基2-苯甲酰胺基-3-（叔丁基二甲基甲硅烷基）氧基）丙酸酯。
• METHODS OF TREATMENT, DIAGNOSIS AND MONITORING FOR METHAMPHETAMINE TOXICITY WHICH TARGET CERAMIDE METABOLIC PATHWAYS AND CELLULAR SENESCENCE
  申请人：The Regents of the University of California

  公开号：US20150148387A1

  公开（公告）日：2015-05-28

  Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis, but the molecular mechanism underlying these findings remains unknown. We report now that methamphetamine accelerates cellular senescence in vitro and activates transcription of genes involved in cell-cycle control and inflammation in vivo by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, generated through methamphetamine metabolism via cytochrome P 450 -2D6, which recruit nuclear factor (NF)-KB to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of ceramide formation prevent methamphetamine-induced senescence and attenuate systemic inflammation and health deterioration in rats self-administering the drug. The results support therapeutic approaches to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of treatments.
• [EN] METHODS OF TREATMENT, DIAGNOSIS AND MONITORING FOR METHAMPHETAMINE TOXICITY WHICH TARGET CERAMIDE METABOLIC PATHWAYS AND CELLULAR SENESCENCE<br/>[FR] PROCÉDÉS DE TRAITEMENT, DE DIAGNOSTIC ET DE SURVEILLANCE DE LA TOXICITÉ DE LA MÉTHAMPHÉTAMINE QUI CIBLENT DES VOIES MÉTABOLIQUES DES CÉRAMIDES ET LA SÉNESCENCE CELLULAIRE
  申请人：UNIV CALIFORNIA

  公开号：WO2013149250A1

  公开（公告）日：2013-10-03

  Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis, but the molecular mechanism underlying these findings remains unknown. We report now that methamphetamine accelerates cellular senescence in vitro and activates transcription of genes involved in cell-cycle control and inflammation in vivo by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, generated through methamphetamine metabolism via cytochrome Pas0-2D6, which recruit nuclear factor (NF)-KB to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of ceramide formation prevent methamphetamine-induced senescence and attenuate systemic inflammation and health deterioration in rats self- administering the drug. The results support therapeutic approaches to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of treatments.