(R)-3-羟基十四烷酸叔丁酯 | 79816-65-2

• 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: (R)-3-羟基十四烷酸叔丁酯
• 英文名称: tert-butyl (R)-3-hydroxytetradecanoate
• 英文别名: (R)-tert-butyl 3-hydroxytetradecanoate；tert-butyl (3R)-3-hydroxytetradecanoate
• CAS: 79816-65-2
• 化学式: C₁₈H₃₆O₃
• 分子量: 300.482
• InChiKey: YZKBUDROMWIDFT-MRXNPFEDSA-N

物化性质

• 沸点：
  394.7±15.0 °C(Predicted)
• 密度：
  0.918±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  21
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-羟基十四烷酸叔丁酯 在 三氟甲磺酸 、 三氟乙酸 作用下， 以 二氯甲烷 、 环己烷 为溶剂， 反应 22.5h， 生成 R-(3)-苄氧基肉豆蔻酸
  参考文献：
  名称：

  On a practical synthesis of β-hydroxy fatty acid derivatives

  摘要：

  An efficient synthesis of three homochiral beta-hydroxy fatty acid derivatives, which have been utilized in our total synthesis of lipid A, is reported. The synthesis features Sharpless asymmetric dihydroxylation of an unsaturated ester, regioselective conversion of a diol into acyloxy chlorides, and a reductive removal of the chloro group.

  DOI：

  10.1016/0957-4166(95)00106-y
• 作为产物：
  描述：

  1-碘癸烷 在 [(S)-2,2'-双(二苯基磷)-1,1'-联萘]二氯化钌(II) 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 73.17h， 生成 (R)-3-羟基十四烷酸叔丁酯
  参考文献：
  名称：

  Efficient Syntheses of a Series of Trehalose Dimycolate (TDM)/Trehalose Dicorynomycolate (TDCM) Analogues and Their Interleukin-6 Level Enhancement Activity in Mice Sera

  摘要：

  We found an IL-6 level-enhancing compound during our synthetic study of trehalose-6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use. In 1993, Datta and Takayama reported the purification of trehalose-6,6'-dicorynomycolate (2c, TDCM) from Corynebacterium spp. We have previously reported the synthesis of four diastereomeric TDCMs and showed that the synthetic (2R,3R,2'R,3'R)-TDCM (2c, hereafter abbreviated RRRR-TDCM-C-14) is identical to natural TDCM; we also demonstrated that 2c and SSSS-TDCM-C-14 (3c) showed significant antitumor activity as well as inhibitory activity in experimental lung metastasis based on the immunoadjuvant activity. Furthermore, we found that the significant lethal toxicity in mice by TDM (1) was no longer observed with the shorter-chain analogues of TDCMs. Therefore, we have elucidated that the 2,3-antistereochemistry (RR or SS) of the fatty acid residue is promising for biological activities. The chain length of the fatty acid residue should also be important for the biological activity, and thus, we designed a general synthetic procedure for trehalose diesters with 2,3-antistereochemistry and a series of chain lengths by using Noyori's asymmetric reduction of beta,beta-ketoesters followed by antiselective alkylation according to Frater to give beta,beta-hydroxy alcohols as the key steps. Thus, we prepared trehalose diesters (TDCM) 2a-d, 3a-d, and 4a-d as well as monoesters (TMCM) 5a-d and 6a-d. Immunological activities of TDCMs and TMCMs were evaluated by determining IL-6 level enhancement in mouse serum, and we found that RRRR-TDCM-C-14 (2c) and RRSS-TDCM-C-14 (4c) showed significant IL-6 level enhancement activities.

  DOI：

  10.1021/jo062018j

文献信息

• Self-Adjuvanting Cancer Vaccines from Conjugation-Ready Lipid A Analogues and Synthetic Long Peptides
  作者：Niels R. M. Reintjens、Elena Tondini、Ana R. de Jong、Nico J. Meeuwenoord、Fabrizio Chiodo、Evert Peterse、Herman S. Overkleeft、Dmitri V. Filippov、Gijsbert A. van der Marel、Ferry Ossendorp、Jeroen D. C. Codée

  DOI：10.1021/acs.jmedchem.0c00851

  日期：2020.10.22

  conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target

  抗原肽与免疫刺激剂共价结合的自佐剂疫苗已被证明是用于免疫疗法的有前途的工具。合成的Toll样受体（TLR）配体是与肽或蛋白质共价连接的理想佐剂。在此，我们在新型偶联物-疫苗形式的产生中，引入了偶联准备就绪的TLR4配体CRX-527，一种有效的强大脂质A类似物。已经开发了用于结合准备的配体的合成以及其与肽抗原的连接的有效化学。探索了不同的接头系统和模型肽的连接模式，并在体外对缀合物的评估显示它们是强大的免疫激活剂，比单独的成分更有效。将CRX-527配体安装在模型肽抗原的N末端可提供一种疫苗形式，该疫苗形式被证明可有效激活树突状细胞，促进抗原呈递以及启动特异性CD8 + T细胞介导的抗原杀伤体内加载的靶细胞。因此，合成的TLR4配体在增强缀合疫苗平台用于癌症疫苗接种中显示出巨大的希望。
• [EN] BIFUNCTIONAL COMPOUND AND ITS USE IN IMMUNOTHERAPY<br/>[FR] COMPOSÉ BIFONCTIONNEL ET SON UTILISATION EN IMMUNOTHÉRAPIE
  申请人：CONSEJO SUPERIOR INVESTIGACION

  公开号：WO2021023512A1

  公开（公告）日：2021-02-11

  The invention relates to a bifunctional compound that is, on one side, an agonist of the TLR4 and, on the other side, an important inhibitor of the PSMA. Said compound is useful in immunotherapy for the treatment and/or prevention of prostate cancer. Therefore, the invention also relates to the use of the compound and to the pharmaceutical composition comprising it.

  这项发明涉及一种双功能化合物，一方面是TLR4的激动剂，另一方面是PSMA的重要抑制剂。该化合物在免疫疗法中用于治疗和/或预防前列腺癌。因此，该发明还涉及该化合物的使用以及包含该化合物的药物组合物。
• [EN] TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME<br/>[FR] LIPOPEPTIDES AGONISTES DU RÉCEPTEUR 2 DE TYPE TOLL, ET PROCÉDÉ DE FABRICATION DE CEUX-CI
  申请人：UNIV KANSAS

  公开号：WO2014113634A1

  公开（公告）日：2014-07-24

  The present disclosure is directed to a novel class of toll-like receptor 2-agnonistic (TLR2) lipopeptide compounds having specific structures, and synthetic methods of making the compounds. These compounds provide high potency of agonistic activities with human, other than murine, TLR2, and are useful as vaccine adjuvants. Vaccines are perhaps one of the most successful medical interventions against infectious disease.

  本公开涉及一类新型的特定结构的类胜肽化的类Toll样受体2激动剂（TLR2）脂肽化合物，以及制备这些化合物的合成方法。这些化合物在人类TLR2中具有高激动活性，并可用作疫苗佐剂。疫苗可能是针对传染病最成功的医学干预之一。
• TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME
  申请人：UNIVERSITY OF KANSAS

  公开号：US20150337009A1

  公开（公告）日：2015-11-26

  The present disclosure is directed to a novel class of toll-like receptor 2-agonistic (TLR2) lipopeptide compounds having specific structures, and synthetic methods of making the compounds. These compounds provide high potency of agonistic activities with human, other than murine, TLR2, and are useful as vaccine adjuvants. Vaccines are perhaps one of the most successful medical interventions against infectious disease.

  本公开涉及一种新型的具有特定结构的Toll样受体2-激动剂（TLR2）脂肽化合物及其合成方法。这些化合物在人类（而非小鼠）的TLR2上具有高效的激动活性，并可用作疫苗佐剂。疫苗可能是预防传染病最成功的医疗干预措施之一。
• Duthaler, Rudolf O.; Herold, Peter; Lottenbach, Willy, Angewandte Chemie, 1989, vol. 101, # 4, p. 490 - 491
  作者：Duthaler, Rudolf O.、Herold, Peter、Lottenbach, Willy、Oertle, Konrad、Riediker, Martin

  DOI：——

  日期：——