8-epi-psymberin

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-epi-psymberin
• 英文别名: (2S,3S)-N-[(R)-[(2S,4R,6R)-6-[(2S,3R)-3-[(3R)-6,8-dihydroxy-5-methyl-1-oxo-3,4-dihydroisochromen-3-yl]-2-hydroxybutyl]-4-hydroxy-5,5-dimethyloxan-2-yl]-methoxymethyl]-2-hydroxy-3-methoxy-5-methylhex-5-enamide
• 化学式: C₃₁H₄₇NO₁₁
• 分子量: 609.714
• InChiKey: BNNIEBYABSNREN-RTJGSMDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  184
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,4-二甲氧基甲苯 在 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 氯化亚砜 、 palladium 10% on activated carbon 、 二氯苯酚溴酯 、 四丁基氟化铵 、 氢气 、 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 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 环己烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 、 苯 为溶剂， 反应 125.0h， 生成 8-epi-psymberin
  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

• Total Synthesis and Biological Evaluation of Pederin, Psymberin, and Highly Potent Analogs
  作者：Shuangyi Wan、Fanghui Wu、Jason C. Rech、Michael E. Green、Raghavan Balachandran、W. Seth Horne、Billy W. Day、Paul E. Floreancig

  DOI：10.1021/ja207331m

  日期：2011.10.19

  N-acyl aminal and functional groups in the two major subunits on biological activity. These analogs, including a pederin/psymberin chimera, were analyzed for their growth inhibitory effects, revealing several new potent cytotoxins and leading to postulates regarding the molecular conformational and hydrogen bonding patterns that are required for biological activity. Second generation analogs have been

  有效的细胞毒素 pederin 和 psymberin 是通过简洁的合成路线（最长线性序列中分别为 10 和 14 步）制备的，这些路线通过后期多组分方法构建 N-酰基氨基键。该路线允许轻松制备许多类似物，这些类似物旨在探索 N-酰基氨基中的烷氧基和两个主要亚基中的官能团对生物活性的重要性。这些类似物，包括 pederin/psymberin 嵌合体，分析了它们的生长抑制作用，揭示了几种新的有效细胞毒素，并导致关于生物活性所需的分子构象和氢键模式的假设。第二代类似物已根据初始测定的结果和这些化合物与核糖体结合的基于结构的模型制备。报道了这些化合物的生长抑制特性。这些研究表明，一般的有机化学，特别是后期多组分反应，在开发独特而有效的生物反应效应物方面可以发挥深远的作用。
• 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。
• IRCINIASTATIN ANALOGUES
  申请人：THE TRUSTEE OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US20150344462A1

  公开（公告）日：2015-12-03

  The present invention is directed to irciniastatin analogues. Uses of these analogues also described.
• US9540355B2
  申请人：——

  公开号：US9540355B2

  公开（公告）日：2017-01-10