methyl 2-[(6S,9S,14aS,15S,16S,20S,23S,25aS,2R,11R)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((1R)-1-hydroxyethyl)-20-hydroxymethyl-16-methyl-9-(11-methyltridecylcarboxamido)-5,8,14,19,22,25-hexaoxoperhydrodiazolo[2,1-c:1-l][1,4,7,10,13,16]hexaazacyclohenicosin-12-ylsulfanyl]acetate | 321661-48-7

• 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
• 英文名称: methyl 2-[(6S,9S,14aS,15S,16S,20S,23S,25aS,2R,11R)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((1R)-1-hydroxyethyl)-20-hydroxymethyl-16-methyl-9-(11-methyltridecylcarboxamido)-5,8,14,19,22,25-hexaoxoperhydrodiazolo[2,1-c:1-l][1,4,7,10,13,16]hexaazacyclohenicosin-12-ylsulfanyl]acetate
• CAS: 321661-48-7
• 化学式: C₅₁H₈₁N₇O₁₇S
• 分子量: 1096.31
• InChiKey: KZABDGBMHAAADM-HTCRRTCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.67
• 重原子数：
  76.0
• 可旋转键数：
  21.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  374.26
• 氢给体数：
  13.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  methyl 2-[(6S,9S,14aS,15S,16S,20S,23S,25aS,2R,11R)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((1R)-1-hydroxyethyl)-20-hydroxymethyl-16-methyl-9-(11-methyltridecylcarboxamido)-5,8,14,19,22,25-hexaoxoperhydrodiazolo[2,1-c:1-l][1,4,7,10,13,16]hexaazacyclohenicosin-12-ylsulfanyl]acetate 在 Oxone 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 以84.9%的产率得到methyl 2-[(6S,9S,14aS,15S,16S,20S,23S,25aS,2R,11R)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((1R)-1-hydroxyethyl)-20-hydroxymethyl-16-methyl-9-(11-methyltridecylcarboxamido)-5,8,14,19,22,25-hexaoxoperhydrodiazolo[2,1-c:1-l][1,4,7,10,13,16]hexaazacyclohenicosin-12-ylsulfonyl]acetate
  参考文献：
  名称：

  Cyclohexapeptide compounds, processes for their production and their use as a pharmaceutical

  摘要：

  通用式（I）的环己六肽化合物，其中R1为C1–C20烷基；C9–C20烯基；C9–C20烷氧基苯基；从以下选择的芳基：苯基，联苯基，三苯基和萘基；C1–C12烷基苯基，C2–C12烯基苯基，C1–C12烷氧基苯基；亚油酰基；棕榈酰基；12-甲基肉豆蔻酰基；10,12-二甲基肉豆蔻酰基；或—COC6H4（p）OC8H17，R1和R3独立地为—OH；—CN；—CH2NH2；—N3；芳基；取代芳基；杂环烷基和带有1–3个相同或不同杂原子的取代杂环烷基；氨基烷基氨基；单取代或双取代的线性或环状氨基烷基氨基；—OR，其中，R为C1–C12烷基；类型为—（CH2）n—X的取代烷基，其中n为1–5，X为Cl，Br，I，COOY，CN，NH2或杂环烷基，Y为C1–C6线性或支链烷基；C2–C12-烯基；芳基；融合芳基；取代芳基；含有1–3个杂原子的杂环烷基；单取代或双取代氨基烷基；或羟基保护基；R3还可以是咪唑基；R2和R4独立地为—H或—OH；R5为—H或—CH3，R6为—H，—CH3或—CH2CONH2。R7为—H，—CH3或—OH。R8和R9独立地为—H或—CH2-Sec.胺，其中Sec.胺通过其N连接与—CH2连接；及其药学上可接受的盐。这些化合物可用作抗真菌剂。

  公开号：

  US07166572B1
• 作为产物：
  描述：

  巯基乙酸甲酯 、 mulundocandin 在 对甲苯磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 methyl 2-[(6S,9S,14aS,15S,16S,20S,23S,25aS,2R,11R)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((1R)-1-hydroxyethyl)-20-hydroxymethyl-16-methyl-9-(11-methyltridecylcarboxamido)-5,8,14,19,22,25-hexaoxoperhydrodiazolo[2,1-c:1-l][1,4,7,10,13,16]hexaazacyclohenicosin-12-ylsulfanyl]acetate
  参考文献：
  名称：

  Approaches towards the stabilization of hemiaminal function at ornithine unit of mulundocandin

  摘要：

  Semisynthetic modifications at position-12 (ornithine-5-position, hemiaminal function) of mulundocandin were carried out to improve its chemical stability. New carbon-carbon (C-C) and carbon-hydrogen (C-H) linkage at hemiaminal function -12 has been achieved. Lewis acid catalyzed introduction of electron rich aryl group at position-12 of mulundocandin is developed. Synthesized mulundocandin analogues were evaluated for their chemical stability and antifungal activity against C. albicans and A. fumigatus. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.084

文献信息

• Semisynthetic modifications of hemiaminal function at ornithine unit of mulundocandin, towards chemical stability and antifungal activity
  作者：Bansi Lal、Vitthal Genbhau Gund、Ashok Kumar Gangopadhyay、S.R. Nadkarni、Vidula Dikshit、D.K. Chatterjee、R. Shirvaikar

  DOI：10.1016/j.bmc.2003.08.003

  日期：2003.11

  Mulundocandin (1), is an echinocandin class of lipopeptide. It has wide spectrum of antifungal activity against Candida and Aspergillus species. Semisynthetic modification at Ornithine-5-hydroxyl (hemiaminal function) of 1 was carried out to improve solution stability and hence in vivo activity. Synthesis of ether (C-OR), thioether (C-SR) and C-N linkage at hemiaminal function have been described. All synthetic analogues were evaluated for their stability in aqueous solution and found to be more stable than mulundocandin. Antifungal activity of Orn-5 analogues was evaluated both in vitro against Candida albicans and Aspergillus famigatus by agar well method and in vivo (oral and intraperitoneal) in C. albicans infected Swiss mice. Results of in vivo assays of analogues 2-9 by the oral route suggests that the introduction of either oxygen nucleophiles (-OR) or sulphur nucleophiles (-SR), at either Orn-5 or at both Orn-5 and HTyr-4 positions, results in retaining the activity of the parent compound with improved aqueous stability in most cases. Compound 9 has shown improved antifungal activity in comparison to mulundocandin by oral application in Swiss mice. (C) 2003 Elsevier Ltd. All rights reserved.