6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one | 135425-66-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one
• 英文别名: 6-ethyl-2,2,5-trimethyl-1,3-dioxin-4-one
• CAS: 135425-66-0
• 化学式: C₉H₁₄O₃
• 分子量: 170.208
• InChiKey: BLPJBNPHCHJXJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one 在 草酰氯 、 二甲基亚砜 、 三乙胺 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 6-(1-methyl-2-oxopropyl)-2,2,5-trimethyl-4H-1,3-dioxin-4-one
  参考文献：
  名称：

  Mechanism and Stereospecificity of a Fully Saturating Polyketide Synthase Module: Nanchangmycin Synthase Module 2 and Its Dehydratase Domain

  摘要：

  Recombinant nanchangmycin synthase module 2 (NANS module 2), with the thioesterase domain from the 6-deoxyerythronolide B synthase (DEBS TE) appended to the C-terminus, was cloned and expressed in Escherichia coli. Incubation of NANS module 2+TE with (+/-)-2-methyl-3-keto-butyryl-N-acetylcysteamine thioester (1), the SNAC analog of the natural ACP-bound substrate, with methylmalonyl-CoA (MM-CoA) in the absence of NADPH gave 3,5,6-trimethy1-4-hydroxypyrone (2), identified by direct comparison with synthetic 2 by radio-TLC-phosphorimaging and LC-ESI(+)-MS-MS. The reaction showed K(cat) 0.5 +/- 0.1 min(-1) and K(m)(1) 19 +/- 5 mM at 0.5 mM MM-CoA and k(cat)(app) 0.26 +/- 0.02 min(-1) and K(m)(MM-CoA) 0.11 +/- 0.02 mM at 8 mM 1. Incubation in the presence of NADPH generated the fully saturated triketide chain elongation product as a 5:3 mixture of (2S,4R)-2,4-dimethy1-5-ketohexanoic acid (3a) and the diastereomeric (2S, 4S)-3b. The structure and stereochemistry of each product was established by comparison with synthetic 3a and 3b by a combination of radio-TLC-phosphorimaging and LC-ESI(-)-MS-MS, as well as chiral capillary GC-MS analysis of the corresponding methyl esters 3a-Me and 3b-Me. The recombinant dehydratase domain from NANS module 2, NANS DH2, was shown to catalyze the formation of an (E)-double bond by syndehydration of the ACP-bound substrate anti-(2R,3R,4S,5R)-2,4-dimethyl-3,5-dihydroxyheptanoyl-ACP6 (4), generated in situ by incubation of (2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][AT6] didomain and ACP6 from DEBS module 6 along with the ketoreductase from the tylactone synthase module 1 (TYLS KR1). These results also indirectly establish the stereochemistry of the reactions catalyzed by the KR and enoylreductase (ER) domains of NANS module 2.

  DOI：

  10.1021/ja1073432
• 作为产物：
  描述：

  丙酸叔丁酯 在 正丁基锂 、 硫酸 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 为溶剂， 反应 5.0h， 生成 6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one
  参考文献：
  名称：

  Large-scale preparation of key building blocks for the manufacture of fully synthetic macrolide antibiotics

  摘要：

  全合成大环内酯的生产关键组分首次在 pilot plant 和小规模试验中进行了扩大生产。这些关键组分不仅支持了新型大环内酯抗生素的发现，也为正在进行的前临床研究提供了支持。

  DOI：

  10.1038/ja.2017.116

文献信息

• An Efficient Directed Claisen Reaction Allows for Rapid Construction of 5,6-Disubstituted 1,3-Dioxin-4-ones
  作者：Andrew Myers、Ziyang Zhang、Yoshiaki Kitamura

  DOI：10.1055/s-0034-1378822

  日期：——

  chromatography and is amenable to large-scale synthesis. An efficient directed Claisen reaction between tert-butyl propionate and phenyl propionate is described. This enables a practical synthesis of 6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one and thereby (Z)-[(4-ethylidene-2,2,5-trimethyl-4H-1,3-dioxin-6-yl)oxy]trimethylsilane, a key building block in our synthesis of macrolide antibiotics. The three-step

  摘要 描述了丙酸叔丁酯和丙酸苯酯之间的有效的定向克莱森反应。这使得能够实际合成6-乙基-2,2,5-三甲基-4H -1,3-二恶英-4-酮，从而合成（Z）-[（4-亚乙基-2,2,5-三甲基-4 H -1,3-二恶英-6-基）氧基]三甲基硅烷，是我们合成大环内酯类抗生素的重要组成部分。用于制备后一种物质的精心设计的三步路线无需色谱，可进行大规模合成。 描述了丙酸叔丁酯和丙酸苯酯之间的有效的定向克莱森反应。这使得能够实际合成6-乙基-2,2,5-三甲基-4H -1,3-二恶英-4-酮，从而合成（Z）-[（4-亚乙基-2,2,5-三甲基-4 H -1,3-二恶英-6-基）氧基]三甲基硅烷，是我们合成大环内酯类抗生素的重要组成部分。用于制备后一种物质的精心设计的三步路线无需色谱，可进行大规模合成。
• Novel, male-produced aggregation pheromone of the cerambycid beetle Rosalia alpina, a priority species of European conservation concern
  作者：Alenka Žunič Kosi、Yunfan Zou、Michal Hoskovec、Al Vrezec、Nataša Stritih、Jocelyn G. Millar

  DOI：10.1371/journal.pone.0183279

  日期：——

  pyrone captured both sexes of R. alpina, indicating that the pyrone functions as an aggregation pheromone. Our results represent the first example of a new structural class of pheromones within the Cerambycidae, and demonstrate that pheromone-baited traps can provide a useful tool for sampling R. alpina. This tool could be particularly useful in the ongoing development of conservation strategies for

  最近的一些研究表明，在生态学和保护学研究中利用符号化学的巨大潜力。cerambycid甲虫Rosalia alpina代表欧洲腐胺类昆虫生物多样性的旗舰物种之一。近年来，由于森林管理和城市化，其人口似乎大大减少了，其范围也大大缩小了。在这里，我们收集了R的雄性和雌性释放的挥发性化学物质。阿尔皮娜（Alpina）。所得提取物的分析表明存在单一的雄性特异性化合物，该化合物被鉴定为新颖的烷基化吡喃酮结构。在斯洛文尼亚的现场生物测定中，用合成吡喃酮诱饵的诱捕器捕获了R的两个性别。alpina，表明吡喃酮起聚集信息素的作用。我们的结果代表了天牛科内信息素新结构类别的第一个例子，并证明了信息素诱集的诱捕器可以为采样R提供有用的工具。阿尔皮纳。该工具在标志性但濒临灭绝的高山长颈鹿保护战略的不断发展中可能特别有用。
• [EN] 14-MEMBERED KETOLIDES AND METHODS OF THEIR PREPARATION AND USE<br/>[FR] KÉTOLIDES À 14 CHAÎNONS ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：HARVARD COLLEGE

  公开号：WO2016057798A1

  公开（公告）日：2016-04-14

  Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macrocyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.

  本文提供了一种制备新的14元环酮类化合物的方法，通过将东半部分和西半部分偶联，然后进行大环化，以及可选的官能化。还提供了合成这些酮类化合物的中间体，包括东部和西部部分。还提供了使用这些酮类化合物治疗传染病和炎症性疾病的药物组合物和方法。
• Total Synthesis of Aetheramide A
  作者：Lisa Gerstmann、Markus Kalesse

  DOI：10.1002/chem.201602682

  日期：2016.8.1

  The first total synthesis of the highly potent anti‐HIV natural product aetheramide A was accomplished in 18 steps from four equally complex building blocks. The synthesis established the unknown configuration at C26 and used a configurationally labile β‐ketoester moiety for the self‐adjustment of the configuration at a methyl branch. The pivotal macrolactamization was achieved by trapping a thermally

  高效的抗HIV天然产物aetheramide A的第一个全合成是通过四个同样复杂的结构单元以18个步骤完成的。合成在C26处建立了未知构型，并使用构型不稳定的β-酮酸酯部分进行甲基分支构型的自我调节。关键的大内酰胺化是通过捕获由其相应的二恶英酮衍生的热生成的酰基乙烯酮来实现的。
• C-phosphorylation of enolates: an alternate route to complex carbonyl-activated phosphonates
  作者：Robert K. Boeckman、Theodore M. Kamenecka、Scott G. Nelson、James R. Pruitt、Thomas E. Barta

  DOI：10.1016/s0040-4039(00)78790-9

  日期：1991.6

  A one-pot two-step phosphorylation procedure is described which is suitable for the preparation of thermally lacible or highly substituted dialkyl phosphonates for use in Horner-Emmons olefinations. Such systems are not readily available using the traditional methods such as the Arbuzov reaction or acylation of dialkyl phosphonate carbanions. Reaction of dioxinone lithium enolates with diethyl chlorophosphite

  描述了一种一锅两步磷酸化方法，该方法适合于制备用于霍纳-埃蒙斯（Horner-Emmons）烯烃化反应的可热交联或高度取代的二烷基膦酸酯。使用传统方法，例如Arbuzov反应或膦酸二烷基碳负离子的酰化反应，这种系统不易获得。二恶英烯醇酸锂与氯代亚磷酸二乙酯反应，然后氧化，以良好或优异的收率和转化率提供所需的膦酸酯。