<2S,3S>-3-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-2-methyl-4-(phenylmethoxy)butanal | 162255-09-6

• 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: <2S,3S>-3-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-2-methyl-4-(phenylmethoxy)butanal
• 英文别名: (2S,3S)-4-(Benzyloxy)-3-((tert-butyldimethylsilyl)oxy)-2-methylbutanal；(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methyl-4-phenylmethoxybutanal
• CAS: 162255-09-6
• 化学式: C₁₈H₃₀O₃Si
• 分子量: 322.52
• InChiKey: HTKGQFWRPXGGGP-NVXWUHKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.43
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  <2S,3S>-3-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-2-methyl-4-(phenylmethoxy)butanal 在 吡啶 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 copper(l) iodide 、 4 A molecular sieve 、 potassium tert-butylate 、 二异丁基氢化铝 、 (+)-Weinsaeure-diethylester 作用下， 以 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 9.0h， 生成 Toluene-4-sulfonic acid (2R,3R,4R,5S)-6-benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-2,4-dimethyl-hexyl ester
  参考文献：
  名称：

  Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships

  摘要：

  The enantioselective total synthesis of aplyronine A (1), a potent antitumor substance of marine origin, was achieved by a convergent-approach Three segments 4, 5, and 6, corresponding to the C5-C11, C21-C27, and C28-C34 portions of aplyronine A (1), were prepared using:the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by julia olefination with sulfone 8 gave the C5-C20 segment 9, while the julia coupling reaction between segments 5 and 6 provided the C21-C34 segment 10. Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B (2) acid C (3), was also carried out using the intermediates for the synthesis of 1, which determined the absolute stereostructures of 2 and 3 unambiguously. To study the structure-cytotoxicity relationships of aplyronines, artificial analogues of 1 were synthesized and their cytotoxicities were evaluated: the trimethylserine moiety, two hydroxyl groups, and the side-chain portion in 1 turned out to be important in the potent cytotoxicity shown by 1. Biological studies with aplyronine A (1) showed that 1 inhibited polymerization of G-actin to F-actin and depolymerized F-actin to G-actin.

  DOI：

  10.1021/jo9606113
• 作为产物：
  描述：

  (4S,5R)-3-[(2S,3S)-3-hydroxy-2-methyl-4-phenylmethoxybutanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one 在 咪唑 、 三甲基铝 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 9.0h， 生成 <2S,3S>-3-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-2-methyl-4-(phenylmethoxy)butanal
  参考文献：
  名称：

  Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships

  摘要：

  The enantioselective total synthesis of aplyronine A (1), a potent antitumor substance of marine origin, was achieved by a convergent-approach Three segments 4, 5, and 6, corresponding to the C5-C11, C21-C27, and C28-C34 portions of aplyronine A (1), were prepared using:the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by julia olefination with sulfone 8 gave the C5-C20 segment 9, while the julia coupling reaction between segments 5 and 6 provided the C21-C34 segment 10. Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B (2) acid C (3), was also carried out using the intermediates for the synthesis of 1, which determined the absolute stereostructures of 2 and 3 unambiguously. To study the structure-cytotoxicity relationships of aplyronines, artificial analogues of 1 were synthesized and their cytotoxicities were evaluated: the trimethylserine moiety, two hydroxyl groups, and the side-chain portion in 1 turned out to be important in the potent cytotoxicity shown by 1. Biological studies with aplyronine A (1) showed that 1 inhibited polymerization of G-actin to F-actin and depolymerized F-actin to G-actin.

  DOI：

  10.1021/jo9606113

文献信息

• Total Synthesis of the Polyether Antibiotic Lonomycin A (Emericid)
  作者：David A. Evans、Andrew M. Ratz、Bret E. Huff、George S. Sheppard

  DOI：10.1021/ja00117a014

  日期：1995.3

  The first asymmetric synthesis of the polyether antibiotic lonomycin has been achieved. The skeleton is assembled through the synthesis and union of two subunits comprising the CI-CII and C12-C3o portions of the structure. These fragments were constructed utilizing auxiliary-based asymmetric aldol and acylation reactions to control the absolute stereochemical relationships in the structure. The majority

  首次不对称合成聚醚类抗生素朗霉素已经实现。骨架是通过两个亚基的合成和结合来组装的，这些亚基包括结构的 CI-CII 和 C12-C30 部分。这些片段是利用基于辅助的不对称醛醇和酰化反应构建的，以控制结构中的绝对立体化学关系。分子聚醚部分中的大部分 1 , Z 氧关系是通过一系列环氧化反应建立的，这些环氧化反应通过分子内杂环化转化为环 D、E 和 F。主要亚基通过高度非对映选择性羟醛反应偶联构建 C11 -C12 键。
• Enantioselective synthesis of δ-/γ-alkoxy-β-hydroxy-α-alkyl-substituted Weinreb amides via DKR–ATH: application to the synthesis of advanced intermediate of (−)-brevisamide
  作者：Gullapalli Kumaraswamy、Akula Narayana Murthy、Vykunthapu Narayanarao、Sahithya Phani Babu Vemulapalli、Jagadeesh Bharatam

  DOI：10.1039/c3ob41088a

  日期：——

  A method of preparing stereodefined δ-/γ-alkoxy-β-hydroxy-α-alkyl-substituted Weinreb amides containing two successive hydroxyl-alkyl stereocenters has been developed. Further, this strategy coupled with organo-catalyzed asymmetric epoxidation culminates in the synthesis of a critical intermediate of (−)-brevisamide and its diastereomers.

  一种制备立体定义的δ-/γ-烷氧基-β-羟基-α-烷基取代的温雷布酰胺的方法已经开发出来。此外，该策略结合了有机催化的不对称环氧化反应，最终合成了(−)-布雷维酰胺及其二叠体的关键中间体。
• Synthesis of a 35-Member Stereoisomer Library of Bistramide A: Evaluation of Effects on actin State, Cell Cycle and Tumor Cell Growth
  作者：Iwona E. Wrona、Jason T. Lowe、Thomas J. Turbyville、Tanya R. Johnson、Julien Beignet、John A. Beutler、James S. Panek

  DOI：10.1021/jo802269q

  日期：2009.3.6

  Synthesis and preliminary biological evaluation of a 35-member library of bistramide A stereoisomers are reported. All eight stereoisomers of the C1−C13 tetrahydropyran fragment of the molecule were prepared utilizing crotylsilane reagents 9 and 10 in our [4+2]-annulation methodology. In addition, the four isomers of the C14−C18 γ-amino acid unit were accessed via a Lewis acid mediated crotylation

  报道了双酰胺 A 立体异构体的 35 成员文库的合成和初步生物学评估。在我们的 [4+2] 环化方法中，使用巴豆基硅烷试剂9和10制备了该分子的 C1-C13 四氢吡喃片段的所有八种立体异构体。此外，C14-C18 γ-氨基酸单元的四种异构体通过路易斯酸介导的巴豆化反应使用有机硅烷11的两种对映异构体获得. Bistramide A 的螺旋缩酮亚基在 C39 醇处进行了修饰，以提供立体化学多样化的另一个点。通过使用标准肽偶联方案将片段偶联以提供天然产物的 35 种立体异构体。筛选这些立体化学类似物对细胞肌动蛋白的影响和对癌细胞系（UO-31 肾和 SF-295 CNS）的细胞毒性。这些测定的结果鉴定了一种类似物1.21，其相对于天然产物 bistramide A 具有增强的效力。
• Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium
  作者：Reiko Ueoka、Philipp Sondermann、Stefan Leopold-Messer、Yizhou Liu、Rei Suo、Agneya Bhushan、Lida Vadakumchery、Ute Greczmiel、Yoko Yashiroda、Hiromi Kimura、Shinichi Nishimura、Yojiro Hoshikawa、Minoru Yoshida、Annette Oxenius、Shigeki Matsunaga、R. Thomas Williamson、Erick M. Carreira、Jörn Piel

  DOI：10.1038/s41557-022-01020-0

  日期：2022.10

  with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of 13C chemical shifts and semiquantitative interpretation of transverse rotating-frame Overhauser effect spectroscopy data were conducted to determine the relative configuration, which enabled the total synthesis of both enantiomers and assignment

  宿主相关细菌越来越被认为是具有前所未有的化学支架的生物活性天然产物的尚未开发的来源。最近发现的一个例子是与植物根相关的海洋细菌Gynuella sunshinyii ，属于海洋螺菌目 (Oceanospirillales)，其化学研究尚未充分。它的基因组包含至少 22 个生物合成基因簇，表明其具有丰富且大多未表征的专门代谢。在这里，对非经典聚酮合酶簇的计算机化学预测导致了贾努他汀的发现，这是一种结构上前所未有的聚酮生物碱，具有强大的细胞毒性，且产量极微。结合MS和二维NMR实验、 13 C化学位移的密度泛函理论计算和横向旋转框架欧豪瑟效应光谱数据的半定量解释，确定了相对构型，从而实现了两种对映体的全合成和归属的绝对配置。 Janusstatins 具有以前未知的吡啶二氢吡喃酮杂环和不寻常的生物活性，包括在亚纳摩尔浓度下延迟、同步的细胞死亡。
• Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships
  作者：Hideo Kigoshi、Kiyotake Suenaga、Tsuyoshi Mutou、Takeshi Ishigaki、Toshiyuki Atsumi、Hiroyuki Ishiwata、Akira Sakakura、Takeshi Ogawa、Makoto Ojika、Kiyoyuki Yamada

  DOI：10.1021/jo9606113

  日期：1996.1.1

  The enantioselective total synthesis of aplyronine A (1), a potent antitumor substance of marine origin, was achieved by a convergent-approach Three segments 4, 5, and 6, corresponding to the C5-C11, C21-C27, and C28-C34 portions of aplyronine A (1), were prepared using:the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by julia olefination with sulfone 8 gave the C5-C20 segment 9, while the julia coupling reaction between segments 5 and 6 provided the C21-C34 segment 10. Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A (1) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B (2) acid C (3), was also carried out using the intermediates for the synthesis of 1, which determined the absolute stereostructures of 2 and 3 unambiguously. To study the structure-cytotoxicity relationships of aplyronines, artificial analogues of 1 were synthesized and their cytotoxicities were evaluated: the trimethylserine moiety, two hydroxyl groups, and the side-chain portion in 1 turned out to be important in the potent cytotoxicity shown by 1. Biological studies with aplyronine A (1) showed that 1 inhibited polymerization of G-actin to F-actin and depolymerized F-actin to G-actin.