sanglifehrin A ketal | 870465-58-0

• 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: sanglifehrin A ketal
• 英文别名: SFA ketal；(1R,4R,7S,10S,16S,19S,21E,23E,25S,26S,27R)-19-[(2E,4E,8S,9S)-10-[(2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undecan-2-yl]-9-hydroxy-8-methyldeca-2,4-dien-2-yl]-10-[(3-hydroxyphenyl)methyl]-1,26-dimethyl-7-propan-2-yl-18,28,29-trioxa-6,9,12,30-tetrazatetracyclo[23.3.1.112,16.04,27]triaconta-21,23-diene-5,8,11,17-tetrone
• CAS: 870465-58-0
• 化学式: C₆₀H₈₉N₅O₁₂
• 分子量: 1072.39
• InChiKey: JBILDDJHMPAXRF-JIHRJFJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  77
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  234
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  sanglifehrin A ketal 在 sodium periodate 、 四氧化锇 、 Hydroquinone 1,4-phthalazinediyl diether 、 甲基磺酰胺 、 硼酸 、 potassium carbonate 、 对甲苯磺酸 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 8.0h， 生成 (2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-2-(((2S,3S)-6-hydroxy-3-methyltetrahydro-2H-pyran-2-yl)methyl)-3,5,11-trimethyl-1-oxa-7-azaspiro[5.5]undecan-8-one
  参考文献：
  名称：

  Toward a Total Synthesis of the Immunosuppressant Sanglifehrin A. Preparation of Two Relay Compounds by Degradation and Their Use in the Reassembly of the Natural Product

  摘要：

  A potential relay route for the synthesis of the novel immunosuppressive agent sanglifehrin A (1) has been developed. Degradation of 1 by a sequence involving regioselective dihydroxylation of the C26,C27 double bond, followed by periodate cleavage of the resulting diol 4, afforded lactol 2 and macrocyclic aldehyde 3. Intramolecular ketal formation between the 1,3-diol and ketone functions present in 3 gave ketal-aldehyde 5. Lactol 2 was converted into sulfone 14 in four steps. The fragments 5 and 14 were reassembled, using the Julia-Kocienski olefination procedure, to afford intermediate 15, which was converted back to sanglifehrin A (1) after two deprotection steps.

  DOI：

  10.1021/jo9912395
• 作为产物：
  描述：

  methyl (S)-2-amino-3-(3-hydroxyphenyl)propanoate 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 三苯胂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 sanglifehrin A ketal
  参考文献：
  名称：

  新型免疫抑制剂 Sanglifehrin A 的全合成

  摘要：

  描述了新型免疫抑制剂 sanglifehrin A (SFA, 1) 的全合成。该方法是灵活的、收敛的和立体选择性的。Paterson 的羟醛方法的使用对于制备新型的、高度取代的 SFA 螺内酰胺片段至关重要。分别使用选择性分子内和分子间 Stille 反应成功实现了分子的 22 元大环核心以及该片段与螺内酰胺部分的偶联。基于碳二亚胺的方案被用于合成三肽骨架。

  DOI：

  10.1021/ja994285v

文献信息

• Efficient Synthesis of [³H]-Sanglifehrin A via Selective Oxidation/Reduction of Alcohols at C₃₁ and C₃₅
  作者：Jürgen Wagner、Hendrik Andres、Stefan Rohrbach、Dieter Wagner、Lukas Oberer、Julien France

  DOI：10.1021/jo051112h

  日期：2005.11.1

  activity and remarkably high affinity for cyclophilin A. To assess its pharmacokinetic properties in vivo, an efficient synthetic route was developed to introduce a tritium label in position C35 of sangliferin A via an oxidation/reduction strategy. The synthetic approach is particularly attractive, because the C35-oxo intermediate 7 is available in good yield on large scale and the reducing agent, lithium

  Sanglifehrin A是一种新型的复杂天然产物，显示出强大的免疫抑制活性和对亲环素A的显着高亲和力。为了评估其体内药代动力学特性，开发了一种有效的合成途径，可通过氧化/在Sangliferin A的C 35位引入introduce标记减少策略。合成方法是特别有吸引力的，因为可以大规模获得高收率的C 35-氧代中间体7，并且很容易获得还原剂三仲丁基三硼化锂。尝试对位置C 31的酒精采用类似策略的尝试主要导致C 31 - Epi-羟基sanglifehrin A在各种条件下。
• Total Synthesis of the Novel Immunosuppressant Sanglifehrin A
  作者：K. C. Nicolaou、F. Murphy、S. Barluenga、T. Ohshima、H. Wei、J. Xu、D. L. F. Gray、O. Baudoin

  DOI：10.1021/ja994285v

  日期：2000.4.1

  The total synthesis of the novel immunosuppressant sanglifehrin A (SFA, 1) is described. The approach is flexible, convergent, and stereoselective. The use of Paterson's aldol methodology was pivotal for the preparation of the novel, highly substituted spirolactam fragment of SFA. The 22-membered macrocyclic core of the molecule and the coupling of this fragment to the spirolactam moiety were successfully

  描述了新型免疫抑制剂 sanglifehrin A (SFA, 1) 的全合成。该方法是灵活的、收敛的和立体选择性的。Paterson 的羟醛方法的使用对于制备新型的、高度取代的 SFA 螺内酰胺片段至关重要。分别使用选择性分子内和分子间 Stille 反应成功实现了分子的 22 元大环核心以及该片段与螺内酰胺部分的偶联。基于碳二亚胺的方案被用于合成三肽骨架。
• Toward a Total Synthesis of the Immunosuppressant Sanglifehrin A. Preparation of Two Relay Compounds by Degradation and Their Use in the Reassembly of the Natural Product
  作者：Rainer Metternich、Donatienne Denni、Binh Thai、Richard Sedrani

  DOI：10.1021/jo9912395

  日期：1999.12.1

  A potential relay route for the synthesis of the novel immunosuppressive agent sanglifehrin A (1) has been developed. Degradation of 1 by a sequence involving regioselective dihydroxylation of the C26,C27 double bond, followed by periodate cleavage of the resulting diol 4, afforded lactol 2 and macrocyclic aldehyde 3. Intramolecular ketal formation between the 1,3-diol and ketone functions present in 3 gave ketal-aldehyde 5. Lactol 2 was converted into sulfone 14 in four steps. The fragments 5 and 14 were reassembled, using the Julia-Kocienski olefination procedure, to afford intermediate 15, which was converted back to sanglifehrin A (1) after two deprotection steps.