14-deoxomyriocin | 156556-20-6

• 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: 14-deoxomyriocin
• 英文别名: (E,2S,3R,4R)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)icos-6-enoic acid
• CAS: 156556-20-6
• 化学式: C₂₁H₄₁NO₅
• 分子量: 387.56
• InChiKey: IRBUWHNHRNBYPA-QRPXNZHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  124
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  14-deoxomyriocin 在 咪唑 、 盐酸 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 [(3S,4R,5R)-3-(tert-Butyl-dimethyl-silanyloxymethyl)-5-((E)-hexadec-2-enyl)-4-hydroxy-2-oxo-tetrahydro-furan-3-yl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Potent Immunosuppressants, 2-Alkyl-2-aminopropane-1,3-diols

  摘要：

  Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft, survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.

  DOI：

  10.1021/jm960391l
• 作为产物：
  描述：

  正十四烷基三苯基溴化膦 在 sodium hydroxide 、 正丁基锂 、 对甲苯磺酸 作用下， 以 乙醇 、 水 为溶剂， 反应 2.83h， 生成 14-deoxomyriocin
  参考文献：
  名称：

  Syntheses, Immunosuppressive Activity, and Structure-Activity Relationships of Myriocin Analogs, 2-epi-Myriocin, 14-Deoxomyriocin, Z-14-Deoxomyriocin, and Nor-deoxomyriocins.

  摘要：

  通过先前合成沙生腊壳菌素（myriocin）和Z-myriocin过程中使用的共同中间体，合成了9种沙生腊壳菌素类似物：2-表-沙生腊壳菌素、14-去氧沙生腊壳菌素、Z-14-去氧沙生腊壳菌素和去甲去氧沙生腊壳菌素。检测了这些沙生腊壳菌素类似物对小鼠异基因混合淋巴细胞反应的免疫抑制活性，发现Z-14-去氧沙生腊壳菌素在其中表现出最强的活性。并讨论了结构-活性关系。

  DOI：

  10.1248/cpb.43.1647

文献信息

• Syntheses of New Immunosuppressive Myriocin Analogs, 2-epi-Myriocin, 14-Deoxomyriocin, Z-14-Deoxomyriocin, and Nor-deoxomyriocins: Their Structure-Activity Relationships.
  作者：Masayuki YOSHIKAWA、Yoshihiro YOKOKAWA、Yasuhiro OKUNO、Nobuhiro YAGI、Nobutoshi MURAKAMI

  DOI：10.1248/cpb.42.2662

  日期：——

  Eight new myriocin analogs, 2-epi-myriocin, Z-14-deoxomyriocin, and nor-deoxomyriocins, and a known myriocin derivative, 14-deoxomyriocin, were synthesized from 2-deoxy-D-glucose via common intermediates in previous myriocin and Z-myriocin syntheses. The immunosuppressive activities of new myriocin analogs and Z-myriocin on mouse allogeneic mixed lymphocyte reaction were examined, and, by comparing with those of myriocin and 14-deoxomyriocin, some structure-activity relationships have been found.

  合成了八种新的米里辛类似物，包括2-epi-myriocin、Z-14-deoxomyriocin和nor-deoxomyriocins，以及一种已知的米里辛衍生物14-deoxomyriocin，这些化合物是通过以往米里辛和Z-myriocin合成中使用的共同中间体，从2-deoxy-D-glucose合成的。对新的米里辛类似物和Z-myriocin在小鼠异体混合淋巴细胞反应中的免疫抑制活性进行了研究，并通过与米里辛和14-deoxomyriocin的比较，发现了一些结构-活性关系。
• Fungal metabolites. Part 12. Potent immunosuppressant, 14-deoxomyriocin, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyleicos-6-enoic acid and structure-activity relationships of myriocin derivatives.
  作者：TETSURO FUJITA、KENICHIRO INOUE、SATOSHI YAMAMOTO、TAKESHI IKUMOTO、SHIGEO SASAKI、RYOUSUKE TOYAMA、KENJI CHIBA、YUKIO HOSHINO、TAKEKI OKUMOTO

  DOI：10.7164/antibiotics.47.216

  日期：——

  In order to investigate the structure-activity relationships, fourteen derivatives of myriocin ((2S', 3R, 4R)-(E)-2-amino-3, 4-dihydroxy-2-hydroxymethyl-14-oxoeicos-6-enoic acid) were prepared and examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction in vitro. Among them, 14-deoxomyriocin ((2S, 3R, 4R)-(E)-2-amino-3, 4-dihydroxy-2-hydroxymethyl-eicos-6-enoic acid) was the most potent. It also suppressed the generation of allo-reactive cytotoxic T lymphocytes in mice upon intraperitoneal administration, with a potency 10-fold greater than that of myriocin.

  为了研究结构与活性之间的关系，我们制备了14种米利霉素（(2S', 3R, 4R)-(E)-2-amino-3, 4-dihydroxy-2-hydroxymethyl-14-oxoeicos-6-enoic acid）衍生物，并检测其对小鼠异体混合淋巴细胞反应的免疫抑制活性。其中，14-脱氧米利霉素（(2S, 3R, 4R)-(E)-2-amino-3, 4-dihydroxy-2-hydroxymethyl-eicos-6-enoic acid）是最有效的。它还能抑制小鼠腹腔注射后产生的异体反应性细胞毒性T淋巴细胞，效力是米利霉素的10倍。
• COMPOSITIONS AND METHODS OF USING COMPOSITIONS WITH ACCELERATED LYMPHOCYTE HOMING IMMUNOSUPPRESSIVE PROPERTIES
  申请人：——

  公开号：US20020102279A1

  公开（公告）日：2002-08-01

  The methods and compositions of the invention and the compounds used in the invention involve a novel immunosuppression mechanism, accelerated lymphocyte homing immunosuppression (ALH-immunosuppression). For example, the compound FTY720 specifically directs lymphocytes to the peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. By reversibly sequestering lymphocytes in these tissues, the compounds can inhibit an immune response in a mammal. Understanding these mechanisms provides a novel immunosuppression therapy that can synergistically interact with other immunosuppressive compounds. Screening methods for identifying similar ALH-immunosuppression compounds are also described. The invention allows better treatments and therapies wherever an immunosuppression regimen is desired.

  本发明的方法和组合物以及本发明中使用的化合物涉及一种新型免疫抑制机制--加速淋巴细胞归巢免疫抑制（ALH-免疫抑制）。例如，化合物 FTY720 能特异性地将淋巴细胞导向外周淋巴结、肠系膜淋巴结和佩耶氏斑块。通过可逆性地将淋巴细胞封闭在这些组织中，化合物可以抑制哺乳动物的免疫反应。了解这些机制可提供一种新型免疫抑制疗法，这种疗法可与其他免疫抑制化合物协同作用。本发明还描述了识别类似 ALH 免疫抑制化合物的筛选方法。本发明可在需要免疫抑制疗法的地方提供更好的治疗和疗法。
• Compositions and methods of using compositions with accelerated lymphocyte homing immunosuppressive properties
  申请人：Mitsubishi Pharma Corporation

  公开号：US20040092603A1

  公开（公告）日：2004-05-13

  The methods and compositions of the invention and the compounds used in the invention involve a novel immunosuppression mechanism, accelerated lymphocyte homing immunosuppression (ALH-immunosuppression). For example, the compound FTY720 specifically directs lymphocytes to the peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. By reversibly sequestering lymphocytes in these tissues, the compounds can inhibit an immune response in a mammal. Understanding these mechanisms provides a novel immunosuppression therapy that can synergistically interact with other immunosuppressive compounds. Screening methods for identifying similar ALH-immunosuppression compounds are also described. The invention allows better treatments and therapies wherever an immunosuppression regimen is desired.

  本发明的方法和组合物以及本发明中使用的化合物涉及一种新型免疫抑制机制--加速淋巴细胞归巢免疫抑制（ALH-免疫抑制）。例如，化合物 FTY720 能特异性地将淋巴细胞导向外周淋巴结、肠系膜淋巴结和佩耶氏斑块。通过可逆性地将淋巴细胞封闭在这些组织中，化合物可以抑制哺乳动物的免疫反应。了解这些机制可提供一种新型免疫抑制疗法，这种疗法可与其他免疫抑制化合物协同作用。本发明还描述了识别类似 ALH 免疫抑制化合物的筛选方法。本发明可在需要免疫抑制疗法的地方提供更好的治疗和疗法。
• US6004565A
  申请人：——

  公开号：US6004565A

  公开（公告）日：1999-12-21