(3S,4R,5R)-3-氨基-4-羟基-3-(羟基甲基)-5-[(E)-10-氧代十六碳-2-烯基]四氢呋喃-2-酮 | 35891-69-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (3S,4R,5R)-3-氨基-4-羟基-3-(羟基甲基)-5-[(E)-10-氧代十六碳-2-烯基]四氢呋喃-2-酮
• 英文名称: Anhydromyriocin
• 英文别名: (3S,4R,5R)-3-amino-4-hydroxy-3-(hydroxymethyl)-5-[(E)-10-oxohexadec-2-enyl]oxolan-2-one
• CAS: 35891-69-1
• 化学式: C₂₁H₃₇NO₅
• 分子量: 383.528
• InChiKey: SWRBTIXRGZAKBN-GNTQXERDSA-N

物化性质

• 沸点：
  510.42°C (rough estimate)
• 密度：
  1.1295 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开存放。

制备方法与用途

类别：有毒物品
毒性分级：高毒
急性毒性：

• 腹腔（大鼠）LD50: 37 毫克/公斤
• 口服（小鼠）LD50: 100 毫克/公斤

可燃性危险特性：可燃；燃烧时产生有毒氮氧化物烟雾

储运特性：应存放在库房内，保持通风、低温和干燥，并与食品原料分开存放

灭火剂：干粉、泡沫、沙土、二氧化碳、雾状水

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R)-3-氨基-4-羟基-3-(羟基甲基)-5-[(E)-10-氧代十六碳-2-烯基]四氢呋喃-2-酮 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 (E)-(3R,4R)-2-Amino-2-hydroxymethyl-icos-6-ene-1,3,4,14-tetraol
  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：

  嗜热菌杀酵母素 在 盐酸 作用下， 以 甲醇 为溶剂， 以78.5%的产率得到(3S,4R,5R)-3-氨基-4-羟基-3-(羟基甲基)-5-[(E)-10-氧代十六碳-2-烯基]四氢呋喃-2-酮
  参考文献：
  名称：

  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.

  摘要：

  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。

  DOI：

  10.7164/antibiotics.47.216

文献信息

• Potent Immunosuppressants, 2-Alkyl-2-aminopropane-1,3-diols
  作者：Tetsuro Fujita、Ryoji Hirose、Masahiko Yoneta、Shigeo Sasaki、Kenichiro Inoue、Masatoshi Kiuchi、Susumu Hirase、Kenji Chiba、Hiroshi Sakamoto、Masafumi Arita

  DOI：10.1021/jm960391l

  日期：1996.1.1

  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.
• 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。