3-壬十二酸 | 145066-77-9

• 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: 3-壬十二酸
• 英文名称: 3-nonyldodecanoic acid
• CAS: 145066-77-9
• 化学式: C₂₁H₄₂O₂
• 分子量: 326.563
• InChiKey: DTPRFTCVNRCFTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  23
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 储存条件：
  保存方法：密闭、阴凉、干燥处

反应信息

• 作为反应物：
  描述：

  3-壬十二酸 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 乙醚 为溶剂， 生成 3-(Nonyl)dodecan-1-ol
  参考文献：
  名称：

  Synthetic Studies on Sialoglycoconjugates 88: Synthesis of Ganglioside GM₃and GM₄Analogs Containing 2- OR 3-Branched Fatty-Alkyl Residues in Place of Ceramide

  摘要：

  Each of four ganglioside GM(4) and GM(3) analogues containing 2- or 3-branched fatty alkyl residues in place of ceramide have been synthesized. Coupling of O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonate)-(2-->3) -2,4,6-tri-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (13) or O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2- nonulopyranosylonate)-(2-->3)-O-(2,4-di-O-acetyl-6-O-benzoyl-beta-D-galactopyranosyl)-(1-->4)-3 -O-acetyl-2,4-di-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (14) with 2- or 3-branched fatty-alkyl-1-ols (9-12), prepared from the corresponding branched fatty acids by methyl esterification and reduction, using BF3 . OEt(2) gave the corresponding ganglioside analogues (15, 17, 19, 21, 23, 25, 27, 29) in good yields, which were coverted, via O-deacylation and de-esterification, into the tide compounds.

  DOI：

  10.1080/07328309608005679
• 作为产物：
  描述：

  正癸酸 在 platinum(IV) oxide 水 、 氢气 、 sodium hydride 、 magnesium 、 N,N'-羰基二咪唑 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 mineral oil 、 正丁醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 34.5h， 生成 3-壬十二酸
  参考文献：
  名称：

  EP2351764

  摘要：

  公开号：

文献信息

• Fully synthetic Mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development
  作者：Xiang Luo、Qinghai Lian、Wenwei Li、Liqing Chen、Renyu Zhang、Deying Yang、Lingqiang Gao、Xiaoxiao Qi、Zhongqiu Liu、Guochao Liao

  DOI：10.1039/d1sc05736g

  日期：——

  these fully synthetic conjugate vaccines do not cause “epitope suppression.” Mincle ligands thus hold great potential as a platform for the development of new vaccine carriers with self-adjuvanting properties for cancer treatment. Preliminary structure–activity relationship analysis shows that a vaccine containing one STn antigen carried by vizantin exhibits the best efficacy, providing support for further

  建立了一种基于巨噬细胞诱导的 C 型凝集素 (Mincle) 激动剂的新策略来构建合成癌症疫苗。使用唾液酸-Tn (STn) 作为模型抗原，通过简单有效的方法设计并合成了四种以 Mincle 激动剂作为内置佐剂的缀合物。所有缀合物都能诱导 BMDM 以 Mincle 依赖性方式产生炎性细胞因子，并且发现仅在小鼠中即可引发强烈的体液和 T 细胞依赖性免疫反应。相应的抗体可以识别、结合 STn 阳性癌细胞并表现出补体依赖性细胞毒性，导致肿瘤细胞裂解。而且，所有缀合物都能有效抑制肿瘤生长，延长小鼠体内存活时间，治疗效果优于STn-CRM197/Al。值得注意的是，与传统的糖蛋白结合疫苗相比，这些全合成结合疫苗不会引起“表位抑制”。因此，Mincle 配体作为开发具有自我辅助癌症治疗特性的新型疫苗载体的平台具有巨大的潜力。初步构效关系分析表明，含有Vizantin携带的一种STn抗原的疫苗表现出最
• Chemical Hybridization of Vizantin and Lipid A to Generate a Novel LPS Antagonist
  作者：Hirofumi Yamamoto、Masataka Oda、Marina Kanno、Shota Tamashiro、Ikuko Tamura、Toshihiko Yoneda、Naoto Yamasaki、Hisanori Domon、Mayo Nakano、Hironobu Takahashi、Yutaka Terao、Yusuke Kasai、Hiroshi Imagawa

  DOI：10.1248/cpb.c15-00828

  日期：——

  Lipopolysaccharide (LPS) antagonists have attracted considerable interest as promising candidates for the treatment of severe sepsis triggered by Gram-negative bacteria. In this article, we describe the development of a novel LPS antagonist based on chemical hybridization of vizantin and the hydrophobic molecular unit of LPS (lipid A). Vizantin, 6,6′-bis-O-(3-nonyldodecanoyl)-α,α′-trehalose, was designed as an immunostimulator from a structure–activity relationship (SAR) study with trehalose 6,6′-dicorynomycolate (TDCM). Our recent study indicated that vizantin displays adjuvant activity by specifically binding to the Toll-like receptor 4 (TLR4)/MD2 protein complex. Because lipid A unit (or LPS) is also known to trigger an inflammatory response via the same TLR4/MD2 complex as vizantin, we designed a hybrid compound of vizantin and lipid A with the aim of developing a novel biofunctional glycolipid. Focusing on the antagonism to Escherichia coli LPS in an in vitro model with human macrophages (THP-1 cells), we identified a potent LPS antagonist among the synthesized hybrid compounds. The novel LPS antagonist effectively inhibited LPS-induced release of tumor necrosis factor-alpha (TNF-α) in a dose-dependent manner with an IC50 value of 3.8 nM, making it a candidate for the treatment drug of Gram-negative sepsis and/or septic shock.

  脂多糖（LPS）拮抗剂作为治疗由革兰氏阴性细菌引发的严重败血症的候选药物，引起了人们的极大兴趣。在这篇文章中，我们介绍了一种新型 LPS 拮抗剂的开发情况，它基于 vizantin 与 LPS 的疏水分子单元（脂质 A）的化学杂交。Vizantin（6,6′-双-O-(3-壬基十二碳酰基)-α,α′-曲哈洛糖）是通过与 6,6′-二硼酸曲哈洛糖（TDCM）的结构-活性关系（SAR）研究而设计的一种免疫刺激剂。我们最近的研究表明，vizantin 通过与 Toll 样受体 4（TLR4）/MD2 蛋白复合物特异性结合而显示出佐剂活性。众所周知，脂质 A 单位（或 LPS）也能通过与 vizantin 相同的 TLR4/MD2 复合物触发炎症反应，因此我们设计了一种 vizantin 和脂质 A 的混合化合物，旨在开发一种新型生物功能糖脂。在以人巨噬细胞（THP-1 细胞）为对象的体外模型中，我们重点研究了大肠杆菌 LPS 的拮抗作用，并在合成的混合化合物中发现了一种强效的 LPS 拮抗剂。这种新型 LPS 拮抗剂能以剂量依赖的方式有效抑制 LPS 诱导的肿瘤坏死因子-α（TNF-α）的释放，其 IC50 值为 3.8 nM，因此可作为革兰氏阴性败血症和/或脓毒性休克的候选治疗药物。
• Lipid structure influences the ability of glucose monocorynomycolate to signal through Mincle
  作者：Phillip L. van der Peet、Masahiro Nagata、Sayali Shah、Jonathan M. White、Sho Yamasaki、Spencer J. Williams

  DOI：10.1039/c6ob01781a

  日期：——

  acid) can substitute for mycolic acid on trehalose and glycerol and maintain robust signalling through Mincle, glucose monobehenate has been reported to be much less active than glucose monocorynomycolate (GMCM). We report the preparation of a range of analogues of GMCM to explore structural requirements in the lipid chain for signalling through Mincle. GMCM analogues bearing simple straight chain or branched

  Mincle（巨噬细胞诱导型C型凝集素）是一种C型凝集素受体，可对多种病原体和常见的糖脂进行免疫感应。Mincle可以从分枝杆菌和棒状杆菌中识别出海藻糖，甘油和葡萄糖的分枝链霉酸和/或corynomycolic酸酯。而简单的直链长脂肪酸（例如山hen酸）可以代替海藻糖和甘油上的麦考酸，并通过Mincle维持强健的信号传导，据报道，山mono酸葡萄糖的活性比葡萄糖基山co糖（GMCM）低得多。我们报道了一系列GMCM类似物的制备，以探索脂质链中通过Mincle进行信号传导的结构要求。带有简单直链或支链脂肪酸酯的GMCM类似物仅通过人和小鼠Mincle提供弱信号。具有截短的（戊基）α链的GMCM变体提供减弱的信号传导，而具有延伸的（三糖基； C23）α链的类似物则具有与GMCM一样强的信号传导。这项工作表明Mincle有能力从放线菌中检测出来源于霉菌的糖脂，从而区分出非致病性（例如红球菌）。s
• Concise Synthesis of a Probe Molecule Enabling Analysis and Imaging of Vizantin
  作者：Hirofumi Yamamoto、Masataka Oda、Mayo Nakano、Kenta Yabiku、Masahiro Shibutani、Toshiyuki Nakanishi、Midori Suenaga、Masahisa Inoue、Hiroshi Imagawa、Masahiro Nagahama、Yoichi Matsunaga、Seiichiro Himeno、Kojun Setsu、Jun Sakurai、Mugio Nishizawa

  DOI：10.1248/cpb.c13-00006

  日期：——

  Trehalose 6,6′-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties. Furthermore, the toxicity of TDCM in mice is much weaker than the related trehalose diester of mycolic acid; trehalose 6,6′-dimycolate (TDM, formerly known as cord factor). We have investigated the chemical modification of this class of compound to generate novel agents that display increased immunoadjuvant activity with minimal associated toxicity. During the course of this work we recently developed 6,6′-bis-O-(3-nonyldodecanoyl)-α,α′-trehalose (designated as vizantin). Our results show that vizantin exhibited a potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells without a loss of body weight and death in mice. Furthermore, vizantin effectively stimulated human macrophages in an in vitro model, making it a promising candidate for a safe adjuvant in clinical applications. In order to elucidate the pharmacokinetics of vizantin, a probe molecule with similar activity was developed on the basis of a structure–activity relationship (SAR) study with vizantin. The distribution of the probe molecule after intravenous administration into a mouse was assessed by macro confocal microscopy, where it was found to accumulate in the lungs and liver.

  Trehalose 6,6′-dicorynomycolate（TDCM）是由 Ioneda 及其合作者于 1963 年首次鉴定出的一种球孢子菌属细胞表面糖脂。由于其免疫佐剂特性，TDCM 具有很强的抗肿瘤活性。此外，TDCM 对小鼠的毒性比相关的霉菌酸曲卤糖二酯（6,6′-dimycolate 曲卤糖，以前称为脐带因子）要弱得多。我们一直在研究对这一类化合物进行化学修饰，以生产出能提高免疫佐剂活性且相关毒性最小的新型制剂。在这一研究过程中，我们最近开发出了 6,6′-双-O-（3-壬基十二碳酰基）-α,α′-曲哈洛糖（命名为 vizantin）。我们的研究结果表明，vizantin 对实验性 B16-F0 黑色素瘤细胞的肺转移具有有效的预防作用，且不会导致小鼠体重下降和死亡。此外，vizantin 还能在体外模型中有效刺激人体巨噬细胞，因此有望成为临床应用中的安全辅助剂。为了阐明 vizantin 的药代动力学，在对 vizantin 进行结构-活性关系（SAR）研究的基础上，开发了一种具有类似活性的探针分子。通过宏观共聚焦显微镜对小鼠静脉注射探针分子后的分布情况进行了评估，发现探针分子在肺部和肝脏中蓄积。
• TREHALOSE COMPOUND, METHOD FOR PRODUCING SAME, AND PHARMACEUTICAL PRODUCT CONTAINING THE COMPOUND
  申请人：Nishizawa Mugio

  公开号：US20110218171A1

  公开（公告）日：2011-09-08

  A trehalose compound having high immunopotentiating activity and low toxicity is represented by formula (1). (In the formula, X and X′ each represents a phenyl, a naphthyl, R 1 —CHR 1 — (wherein R 1 and R 2 each represents a C 7 -C 21 alkyl group or the like) or the like; and n and n′ each independently represents an integer of 0-3). The compound exhibits a high activating effect on macrophages and neutrophils.

  具有高免疫增强活性和低毒性的海藻糖化合物由公式（1）表示。（在公式中，X和X'分别表示苯基，萘基，R1-CHR1-（其中R1和R2各代表C7-C21烷基或类似物），n和n'各自独立地表示0-3的整数）。该化合物对巨噬细胞和中性粒细胞具有高激活作用。