(3S,4R,5E)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-6-phenyl-5-hexenal | 162465-27-2

• 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: (3S,4R,5E)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-6-phenyl-5-hexenal
• 英文别名: (3S,4R)-3-tert-butyldimethylsilanyloxy-4-methyl-6-phenylhex-5(E)-enal；(3S,4R,E)-3-(tert-butyldimethylsilyloxy)-4-methyl-6-phenylhex-5-enal；(E,3S,4R)-3-[tert-butyl(dimethyl)silyl]oxy-4-methyl-6-phenylhex-5-enal
• CAS: 162465-27-2
• 化学式: C₁₉H₃₀O₂Si
• 分子量: 318.531
• InChiKey: QJNDYERJXLAFJC-JXPOREOESA-N

物化性质

• 沸点：
  395.0±42.0 °C(Predicted)
• 密度：
  0.948±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.32
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,4R,5E)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-6-phenyl-5-hexenal 在 4-二甲氨基吡啶 、 二苯基磷酸 、 四丁基氟化铵 、 碳酸氢钠 、 达卡巴嗪 、 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， 生成 desepoxyarenastatin A
  参考文献：
  名称：

  A concise synthesis of the cytotoxic depsipeptide arenastatin A

  摘要：

  Arenastatin A (1, cryptophycin 24) was synthesized by convergence of hydroxy eater 16 with amino acid derivative 27; two independent and highly efficient routes to 16 are disclosed. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)02014-0
• 作为产物：
  描述：

  苯基膦酸二乙酯 在 正丁基锂 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 73.0h， 生成 (3S,4R,5E)-3-[(tert-butyldimethylsilyl)oxy]-4-methyl-6-phenyl-5-hexenal
  参考文献：
  名称：

  Formal syntheses of cryptophycin A and arenastatin A

  摘要：

  Efficient formal syntheses of the tubulin binding antitumor agents cryptophycin A (1) and arenastatin A (2) are detailed. The readily available beta-keto ester 4 was subjected to catalytic asymmetric hydrogenation, Frater alkylation, and selective functional group transformations to provide the silyl ether of octanoic acid methyl ester 3, which is the key intermediate for the formal syntheses of the title compounds. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)00194-9

文献信息

• Cryptophycin compounds
  申请人：Eli Lilly and Company

  公开号：US06680311B1

  公开（公告）日：2004-01-20

  The present invention provides cryptophycin compounds of Formula I that are useful in the treatment of neoplasms.

  本发明提供了一种在肿瘤治疗中有用的Formula I的cryptophycin化合物。
• Total Synthesis of Cryptophycins. Revision of the Structures of Cryptophycins A and C
  作者：Russell A. Barrow、Thomas Hemscheidt、Jian Liang、Seunguk Paik、Richard E. Moore、Marcus A. Tius

  DOI：10.1021/ja00114a011

  日期：1995.3

  The convergent total synthesis of cryptophycins C and D is described. It has been shown that in both natural products the absolute configuration of the a-amino acid corresponds to the D-series. The structural assignment for cryptophycin C has been corrected to reflect this fact. Since the structure of cryptophycin A has been correlated to cryptophycin C, the chloro-0-methyltyrosine unit in cryptophycin

  描述了隐霉素 C 和 D 的收敛全合成。已经表明，在两种天然产物中，α-氨基酸的绝对构型对应于 D 系列。已更正了隐藻素 C 的结构分配以反映这一事实。由于隐藻素A的结构与隐藻素C相关，隐藻素A中的氯-0-甲基酪氨酸单元具有D-构型。隐藻素是与陆生蓝绿藻 Nostoc sp. 相关的强效肿瘤选择性细胞毒素。GSV 224' 和 Nostoc sp。ATCC 53789.2 每种藻类中的主要细胞毒素，cryptophycin A，对植入小鼠的实体瘤（包括耐药性肿瘤）显示出极好的活性。超过 20 种相关的细胞毒素作为次要成分存在于 GSV 224 菌株中，以及这些化合物中的一些，例如，隐藻素 B 和 C，已被分离出足够的量用于体内评估。~为了获得足够数量的选定天然存在的隐藻素和合成类似物，用于构效关系 (SAR) 研究、临床前评估和人类临床试验，我们设计了一个通用的合成。正如原始论文中所述，Cryptophycins
• Flexible Routes to the 5-Hydroxy Acid Fragment of the Cryptophycins
  作者：Prodeep Phukan、Sanjita Sasmal、Martin E. Maier

  DOI：10.1002/ejoc.200210695

  日期：2003.5

  Two solutions to establishing the anti stereochemistry of the vicinal stereocenters in the 5-hydroxy acid subunit of cryptophycin, based on initial Evans syn aldol reactions between an N-(propionyl)oxazolidinone 4 and a C3 aldehyde, were developed. In the first route, the secondary hydroxy group was inverted by use of Mitsunobu reaction conditions, whereas the second route features an inversion of

  基于 N-（丙酰基）恶唑烷酮 4 和 C3 醛之间的初始 Evans Syn aldol 反应，开发了两种解决方案，用于建立 cryptophycin 的 5-羟基酸亚基中的邻位立体中心的反立体化学。在第一条路线中，仲羟基通过使用光信反应条件反转，而第二条路线的特点是带有甲基的立体中心的反转，通过手性助剂的还原去除、消除得到末端烯烃和反-选择性硼氢化。芳基部分可以通过 Wittig-Horner 烯化或修饰的 Julia 偶联连接。两条路线都以非常有效的方式提供羟基酸16。硼氢化的底物烯烃 22 也可以从 (S)-苹果酸获得。(© Wiley-VCH Verlag GmbH & Co.
• Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae
  作者：James D. White、Jian Hong、Lonnie A. Robarge

  DOI：10.1021/jo9907585

  日期：1999.8.1

  A convergent synthesis of cryptophycins has been developed in which (5S,GR)-5-hydroxy-6-methyl-8-phenylocta-2(E),7(E)-dienoic add (A) is coupled with an amino acid. segment (B). Two stereoselective routes to A are described, the first employing allylation of an alpha-homochiral aldehyde and the second using asymmetric crotylation of an achiral aldehyde to establish the two stereogenic centers present in a. The styryl moiety of A was attached either via Stille coupling or through a Wadsworth-Emmons condensation with diethyl benzylphosphonate. The amino acid subunit B was prepared from benzyl (2S)-2-hydroxyisocaproate by connection first to N-Boc-beta-alanine or its (2R)-methyl-substituted derivative and then to (2R)-N-Boc-O-methyltyrosine or its nt-chloro derivative. Fusion of the A and B subunits was accomplished by initial esterification of the former with the latter, followed by macrocyclization using diphenyl phosphorazidate. In this way, cryptophycin-3, -4, and -29 were obtained along with the nonnatural cyclic depsipeptide 52. Epoxidation of cryptophycin-3 with dimethyldioxirane gave cryptophycin-1; analogous epoxidation of 52 afforded arenastatin A (cryptophycin-24).
• Total Synthesis of Cryptophycin-24 (Arenastatin A) Amenable to Structural Modifications in the C16 Side Chain
  作者：MariJean Eggen、Craig J. Mossman、Suzanne B. Buck、Sajiv K. Nair、Laxminarayan Bhat、Syed M. Ali、Emily A. Reiff、Thomas C. Boge、Gunda I. Georg

  DOI：10.1021/jo000767+

  日期：2000.11.1

  Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E,7E)-5-[(tert-butyldimethylsily oxy]-6-methyl-8-phenyl-2,7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl oft-he cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha -pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl(5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6 -methyl-2,7 -octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).