hydroxyphthioceranic acid | 1454597-96-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: hydroxyphthioceranic acid
• 英文别名: (2S,4S,6S,8S,10R,12R,14R,16R,17R)-17-Hydroxy-2,4,6,8,10,12,14,16-octamethyldotriacontanoic acid；(2S,4S,6S,8S,10R,12R,14R,16R,17R)-17-hydroxy-2,4,6,8,10,12,14,16-octamethyldotriacontanoic acid
• CAS: 1454597-96-6
• 化学式: C₄₀H₈₀O₃
• 分子量: 609.073
• InChiKey: HCTBUGXAFRDFOG-LLOKPTLRSA-N

物化性质

• 沸点：
  662.3±28.0 °C(Predicted)
• 密度：
  0.890±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  16.4
• 重原子数：
  43
• 可旋转键数：
  30
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  、 hydroxyphthioceranic acid 在 2,4,6-三氯苯甲酰氯 、 三乙胺 、 4-二甲氨基吡啶 作用下， 反应 49.0h， 生成 (2R,4aR,6R,7R,8S,8aR)-7-(palmitoyloxy)-2-phenyl-6-(((5aR,6R,7aR,10R,11aR,11bS)-2,2,4,4-tetraisopropyl-10-phenylhexahydro-[1,3]dioxino[4',5':5,6]pyrano[3,4-f][1,3,5,2,4]trioxadisilepin-6-yl)oxy)hexahydropyrano[3,2-d][1,3]dioxin-8-yl (2S,4S,6S,8S,10R,12R,14R,16R,17R)-17-hydroxy-2,4,6,8,10,12,14,16-octamethyldotriacontanoate
  参考文献：
  名称：

  CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis

  摘要：

  Mycobacterial cell wall lipids bind the conserved CD1 family of antigen-presenting molecules and activate T cells via their T cell receptors (TCRs). Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis, but tools to study SGL-specific T cells in humans are lacking. We designed a novel hybrid synthesis of a naturally occurring SGL, generated CD1b tetramers loaded with natural or synthetic SGL analogs, and studied the molecular requirements for TCR binding and T cell activation. Two T cell lines derived using natural SGLs are activated by synthetic analogs independently of lipid chain length and hydroxylation, but differentially by saturation status. By contrast, two T cell lines derived using an unsaturated SGL synthetic analog were not activated by the natural antigen. Our data provide a bioequivalence hierarchy of synthetic SGL analogs and SGL-loaded CD1b tetramers. These reagents can now be applied to large-scale translational studies investigating the diagnostic potential of SGL-specific T cell responses or SGL-based vaccines.

  DOI：

  10.1016/j.chembiol.2018.01.006
• 作为产物：
  描述：

  十六醛 在 咪唑 、 9-METHOXY-9-BORABICYCLO[3.3.1]NONANE 、 4-二甲氨基吡啶 、 Candida antarctica lipase B 、 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 偶氮二甲酸二异丙酯 、 (+)-(R)-[1,5-cyclooctadien-7-(2-phenyl-6,7-dihydro-5H-[1]pyridine)-di-(tert-butyl)-phosphinite-iridium(I)]-tetrakis-(3,5-bis(trifluoromethyl)-phenyl)-borate 、 [Ir(cod)(SIMes)(Pyr)]⁺PF₆^- 、 四丁基氟化铵 、 氢气 、 叔丁基锂 、 tetra-N-butylammonium tribromide 、 碳酸氢钠 、 叔丁基二甲基氯硅烷 、 三苯基膦 、 potassium bromide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 正戊烷 为溶剂， -78.0~20.0 ℃ 、9.0 MPa 条件下， 反应 177.0h， 生成 hydroxyphthioceranic acid
  参考文献：
  名称：

  聚合的长链聚脱氧丙酸酯的高立体选择性和灵活的策略：在糖脂膜成分羟硫代ceranic和Phthioceranic酸的合成中的应用

  摘要：

  已经开发了高度立体可控的和灵活的光学纯形式的生物相关聚脱氧丙酸酯的途径。利用我们先前建立的不对称和立体发散的三脱氧丙酸酯结构单元合成策略，我们现在能够以高度收敛的方式组装具有确定构型的大型聚脱氧丙酸酯链。该方法的主要步骤包括两个Suzuki-Miyaura交叉偶联反应，以及随后的非对映选择性加氢反应，以优异的收率和完全的立体化学控制作用，将三个高级合成中间体连接在一起。我们已成功地将此策略应用于糖脂膜成分phthioceranic acid和hydroxyphthioceranic acid的不对称合成，

  DOI：

  10.1002/chem.201404034

文献信息

• Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy
  作者：Ramesh Rasappan、Varinder K. Aggarwal

  DOI：10.1038/nchem.2010

  日期：2014.9

  In planning organic syntheses, disconnections are most often made adjacent to functional groups, which assist in C–C bond formation. For molecules devoid of obvious functional groups this approach presents a problem, and so functionalities must be installed temporarily and then removed. Here we present a traceless strategy for organic synthesis that uses a boronic ester as such a group in a one-pot lithiation–borylation–protodeboronation sequence. To realize this strategy, we developed a methodology for the protodeboronation of alkyl pinacol boronic esters that involves the formation of a boronate complex with a nucleophile followed by oxidation with Mn(OAc)3 in the presence of the hydrogen-atom donor 4-tert-butylcatechol. Iterative lithiation–borylation–protodeboronation allows the coupling of smaller fragments to build-up long alkyl chains. We employed this strategy in the synthesis of hydroxyphthioceranic acid, a key component of the cell-wall lipid of the virulent Mycobacterium tuberculosis, in just 14 steps (longest linear sequence) with full stereocontrol. Coupling of carbamates with boronic esters followed by protodeboronation creates a new carbon–carbon bond, leaving behind no trace of the functional groups used to create it. Now, methodology for the protodeboronation of alkyl pinacol boronic esters has been developed and an iterative lithiation–borylation–protodeboronation strategy used in a 14-step stereocontrolled synthesis of hydroxyphthioceranic acid.

  在计划有机合成时，断链最常发生在官能团附近，有助于碳-碳键的形成。对于没有明显官能团的分子，这种方法提出了一个问题，因此必须暂时安装功能性基团，然后再移除。在这里，我们提出了一种无痕迹的有机合成策略，该策略使用硼酸酯作为在一锅锂化-硼化-去硼化序列中的这种功能基团。为了实现这一策略，我们开发了一种方法，用于对频哪醇硼酸酯的脱硼酸化，该方法涉及与亲核试剂形成硼酸盐络合物，然后在4-叔丁基邻苯二酚的氢原子供体存在下用Mn(OAc)3氧化。迭代锂化-硼化-脱硼化允许将较小片段耦合以构建长烷基链。我们将这一策略应用于制备强毒性结核杆菌细胞壁脂质的关键成分羟基紫胶虫酸的合成中，仅用14步（最长线性序列）就实现了立体控制。通过脱硼化将氨基甲酸酯与硼酸酯结合，可以创建新的碳-碳键，不会留下用于创建该键的官能团的任何痕迹。现在，已经开发出了频哪醇硼酸酯的脱硼化方法，并在14步立体控制合成羟基紫胶虫酸中使用了迭代锂化-硼化-脱硼化策略。
• A Convergent and Stereoselective Synthesis of the Glycolipid Components Phthioceranic Acid and Hydroxyphthioceranic Acid
  作者：Matthias C. Pischl、Christian F. Weise、Marc-André Müller、Andreas Pfaltz、Christoph Schneider

  DOI：10.1002/anie.201303776

  日期：2013.8.19

  Simply convergent: The polydeoxypropionates 1 and 2 are important constituents of the cell wall of Mycobacterium tuberculosis. Key steps in their total synthesis include two Suzuki–Miyaura cross‐coupling reactions and two highly diastereoselective iridium‐catalyzed hydrogenations. The trideoxypropionates employed as central building blocks were prepared by sequential oxy‐Cope rearrangement, hydrogenation

  简单收敛：聚脱氧丙酸酯1和2是结核分枝杆菌细胞壁的重要组成部分。它们全合成的关键步骤包括两个Suzuki-Miyaura交叉偶联反应和两个高度非对映选择性的铱催化的氢化反应。用作中心结构单元的三脱氧丙酸酯是通过顺序的oxy-Cope重排，氢化和烯醇式甲基化制备的。
• Toward Ideality: The Synthesis of (+)-Kalkitoxin and (+)-Hydroxyphthioceranic Acid by Assembly-Line Synthesis
  作者：Sebastien Balieu、Gayle E. Hallett、Matthew Burns、Teerawut Bootwicha、John Studley、Varinder K. Aggarwal

  DOI：10.1021/ja512875g

  日期：2015.4.8

  The iterative homologation of boronic esters using chiral lithiated benzoate esters and chloromethyllithium has been applied to the highly efficient syntheses of two natural products, (+)-kalkitoxin and (+)-hydroxyphthioceranic acid. The chiral lithiated benzoate esters (>99% ee) were generated from the corresponding stannanes, which themselves were prepared by HoppeBeak deprotonation of ethyl 2,4,6-triisopropyl-benzoate with s-BuLi in the presence of (+)- or (-)-sparteine and trapping with Me3SnCl followed by recrystallization. In addition, it was found that purification between several homologations could be avoided, substantially increasing both chemical and manpower efficiency. In the case of (+)-kalkitoxin, six iterative homologations were conducted on commercially available p-MeOC(6)H(4)CH(2)Bpin to build up the core of the molecule before the C-B bond was converted into the desired CN bond, without purification of intermediates. In the case of (+)-hydroxyphthioceranic acid, 16 iterative homologations were conducted on p-MeOC(6)H(4)Bpin with only four intermediate purifications before oxidation of the C-B bond to the desired alcohol. The stereocontrolled and efficient syntheses of these complex molecules highlight the power of iterative chemical synthesis using boronic esters.
• A Highly Stereoselective and Flexible Strategy for the Convergent Synthesis of Long-Chain Polydeoxypropionates: Application towards the Synthesis of the Glycolipid Membrane Components Hydroxyphthioceranic and Phthioceranic Acid
  作者：Matthias C. Pischl、Christian F. Weise、Stefan Haseloff、Marc-André Müller、Andreas Pfaltz、Christoph Schneider

  DOI：10.1002/chem.201404034

  日期：2014.12.22

  polydeoxypropionates in optically pure form has been developed. Taking advantage of our previously established strategy for the asymmetric and stereodivergent synthesis of trideoxypropionate building blocks, we have now been able to assemble large polydeoxypropionate chains with defined configuration in a highly convergent manner. Central steps of this approach include two Suzuki–Miyaura cross‐coupling reactions with

  已经开发了高度立体可控的和灵活的光学纯形式的生物相关聚脱氧丙酸酯的途径。利用我们先前建立的不对称和立体发散的三脱氧丙酸酯结构单元合成策略，我们现在能够以高度收敛的方式组装具有确定构型的大型聚脱氧丙酸酯链。该方法的主要步骤包括两个Suzuki-Miyaura交叉偶联反应，以及随后的非对映选择性加氢反应，以优异的收率和完全的立体化学控制作用，将三个高级合成中间体连接在一起。我们已成功地将此策略应用于糖脂膜成分phthioceranic acid和hydroxyphthioceranic acid的不对称合成，
• CD1b Tetramers Identify T Cells that Recognize Natural and Synthetic Diacylated Sulfoglycolipids from Mycobacterium tuberculosis
  作者：Charlotte A. James、Krystle K.Q. Yu、Martine Gilleron、Jacques Prandi、Vijayendar R. Yedulla、Zuzanna Z. Moleda、Eleonora Diamanti、Momin Khan、Varinder K. Aggarwal、Josephine F. Reijneveld、Peter Reinink、Stefanie Lenz、Ryan O. Emerson、Thomas J. Scriba、Michael N.T. Souter、Dale I. Godfrey、Daniel G. Pellicci、D. Branch Moody、Adriaan J. Minnaard、Chetan Seshadri、Ildiko Van Rhijn

  DOI：10.1016/j.chembiol.2018.01.006

  日期：2018.4

  Mycobacterial cell wall lipids bind the conserved CD1 family of antigen-presenting molecules and activate T cells via their T cell receptors (TCRs). Sulfoglycolipids (SGLs) are uniquely synthesized by Mycobacterium tuberculosis, but tools to study SGL-specific T cells in humans are lacking. We designed a novel hybrid synthesis of a naturally occurring SGL, generated CD1b tetramers loaded with natural or synthetic SGL analogs, and studied the molecular requirements for TCR binding and T cell activation. Two T cell lines derived using natural SGLs are activated by synthetic analogs independently of lipid chain length and hydroxylation, but differentially by saturation status. By contrast, two T cell lines derived using an unsaturated SGL synthetic analog were not activated by the natural antigen. Our data provide a bioequivalence hierarchy of synthetic SGL analogs and SGL-loaded CD1b tetramers. These reagents can now be applied to large-scale translational studies investigating the diagnostic potential of SGL-specific T cell responses or SGL-based vaccines.