(2S,4R,6R)-6-[(2S,3R)-3-[(3R)-6,8-bis[(4-methoxyphenyl)methoxy]-5-methyl-1-oxo-3,4-dihydroisochromen-3-yl]-2-hydroxybutyl]-4-hydroxy-5,5-dimethyloxane-2-carbonitrile | 864514-29-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (2S,4R,6R)-6-[(2S,3R)-3-[(3R)-6,8-bis[(4-methoxyphenyl)methoxy]-5-methyl-1-oxo-3,4-dihydroisochromen-3-yl]-2-hydroxybutyl]-4-hydroxy-5,5-dimethyloxane-2-carbonitrile
• CAS: 864514-29-4
• 化学式: C₃₈H₄₅NO₉
• 分子量: 659.777
• InChiKey: NKKAZJVVXNDYRG-WITSCBGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S,4R,6R)-6-[(2S,3R)-3-[(3R)-6,8-bis[(4-methoxyphenyl)methoxy]-5-methyl-1-oxo-3,4-dihydroisochromen-3-yl]-2-hydroxybutyl]-4-hydroxy-5,5-dimethyloxane-2-carbonitrile 在 palladium on activated charcoal 2-乙烯基吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 (Me₂PO)2HPt(Me₂POH) 、 水 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 40.0 ℃ 、101.33 kPa 条件下， 反应 56.83h， 生成 irciniastatin A
  参考文献：
  名称：

  Psymberin/Irciniastatin A 的合成和完整立体化学分配

  摘要：

  我们描述了一种简洁灵活的合成途径，用于制备结构与新型海洋衍生差异细胞毒素 psymberin 和 irciniastatin A 相关的化合物。我们的努力导致了它们的完整立体化学分配以及 psymberin 和 irciniastatin A 相同的概念化合物。我们的全合成具有从 C2 对称双烯烃前体获得的二醛的有趣的末端差异化乳醇化、差向异构腈的温和铂催化水解、制备灵敏的亚胺酸甲酯的新方案和一锅法转化这些亚胺酯转化为 N-酰基胺。从片段 5-7 开始（每个片段准备 7-8 个步骤，

  DOI：

  10.1021/ja0537068
• 作为产物：
  描述：

  2,4-二甲氧基甲苯 在 sodium periodate 、 四氧化锇 、 氯化亚砜 、 二氯苯酚溴酯 、 四丁基氟化铵 、 仲丁基锂 、 三溴化硼 、 potassium carbonate 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 儿萘酚硼烷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 环己烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 、 苯 为溶剂， 反应 93.0h， 生成 (2S,4R,6R)-6-[(2S,3R)-3-[(3R)-6,8-bis[(4-methoxyphenyl)methoxy]-5-methyl-1-oxo-3,4-dihydroisochromen-3-yl]-2-hydroxybutyl]-4-hydroxy-5,5-dimethyloxane-2-carbonitrile
  参考文献：
  名称：

  Studies toward the Unique Pederin Family Member Psymberin: Full Structure Elucidation, Two Alternative Total Syntheses, and Analogs

  摘要：

  Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, similar to 14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (similar to 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.

  DOI：

  10.1021/ja3057612

文献信息

• Synthesis and Complete Stereochemical Assignment of Psymberin/Irciniastatin A
  作者：Xin Jiang、Jorge García-Fortanet、Jef K. De Brabander

  DOI：10.1021/ja0537068

  日期：2005.8.1

  We describe a concise and flexible synthetic avenue for the preparation of compounds with structures relevant to those proposed for the novel marine-derived differential cytotoxins psymberin and irciniastatin A. Our efforts led to their complete stereochemical assignment and the notion that psymberin and irciniastatin A are identical compounds. Our total synthesis features an interesting termini-differentiating

  我们描述了一种简洁灵活的合成途径，用于制备结构与新型海洋衍生差异细胞毒素 psymberin 和 irciniastatin A 相关的化合物。我们的努力导致了它们的完整立体化学分配以及 psymberin 和 irciniastatin A 相同的概念化合物。我们的全合成具有从 C2 对称双烯烃前体获得的二醛的有趣的末端差异化乳醇化、差向异构腈的温和铂催化水解、制备灵敏的亚胺酸甲酯的新方案和一锅法转化这些亚胺酯转化为 N-酰基胺。从片段 5-7 开始（每个片段准备 7-8 个步骤，
• Synthesis and complete stereochemical assignment of psymberin/irciniastatin for use as antitumor compounds
  申请人：Brabander De Jef

  公开号：US20070015821A1

  公开（公告）日：2007-01-18

  The invention relates to the synthesis and complete stereochemical assignments of cytotoxic compounds such as compound 28-a and its stereoisomers: The invention further provides processes for making the compounds, their synthetic intermediates, and for methods of using the compounds and their pharmaceutical compositions for the treatment of neoplastic diseases.

  该发明涉及合成和对细胞毒性化合物的完全立体化学赋值，如化合物28-a及其立体异构体。该发明还提供了制备这些化合物、它们的合成中间体的方法，以及使用这些化合物及其药物组合物治疗肿瘤性疾病的方法。
• [EN] SYNTHESIS AND COMPLETE STEREOCHEMICAL ASSIGNMENT OF PSYMBERIN/IRCINIASTATIN FOR ANTI-TUMOR USE<br/>[FR] SYNTHESE ET ATTRIBUTION STEREOCHIMIQUE COMPLETE DE PSYMBERINE/IRCINIASTATINE POUR UNE APPLICATION ANTI-TUMORALE
  申请人：UNIV TEXAS

  公开号：WO2007011629A2

  公开（公告）日：2007-01-25

  [EN] The invention relates to the synthesis and complete stereochemical assignments of cytotoxic compounds such as compound 28-a and its stereoisomers. The invention further provides processes for making the compounds, their synthetic intermediates, and for methods of using the compounds and their pharmaceutical compositions for the treatment of neoplastic diseases.
  [FR] La présente invention concerne la synthèse et les attributions stéréochimiques complètes de composés cytotoxiques, tels que le composé 28-a et ses stéréoisomères. La présente invention concerne également des procédés permettant de fabriquer ces composés; leurs produits intermédiaires de synthèse ainsi que des méthodes permettant d'utiliser ces composés et les compositions pharmaceutiques destinées au traitement de maladies néoplasiques.
• Studies toward the Unique Pederin Family Member Psymberin: Full Structure Elucidation, Two Alternative Total Syntheses, and Analogs
  作者：Yu Feng、Xin Jiang、Jef K. De Brabander

  DOI：10.1021/ja3057612

  日期：2012.10.17

  Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, similar to 14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (similar to 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.