methyl 4-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)butanoate | 1042910-21-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)butanoate
• 英文别名: methyl 4-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolane-4-yl)butanoate；Methyl (4S,5R)-5-ethenyl-2,2-dimethyl-1,3-dioxolane-4-butanoate；methyl 4-[(4S,5R)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]butanoate
• CAS: 1042910-21-3
• 化学式: C₁₂H₂₀O₄
• 分子量: 228.288
• InChiKey: ZEBMHIUXGMBWHT-ZJUUUORDSA-N

物化性质

• 沸点：
  279.6±25.0 °C(Predicted)
• 密度：
  1.034±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)butanoate 在 potassium phosphate 、 甲酸 、 Hoveyda-Grubbs catalyst second generation 、 Noyori's catalyst 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 (1S)-(+)-10-camphorsulfonic acid 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 111.75h， 生成 methyl (5S,6R,E)-5,6-dihydroxy-8-(2-((R)-1-hydroxy-2-phenoxyethyl)benzo[b]thiophen-3-yl)oct-7-enoate
  参考文献：
  名称：

  [EN] HETEROCYCLIC LIPOXIN ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE LIPXON HÉTÉROCYCLIQUES ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2018033642A9
• 作为产物：
  描述：

  methyl 4-((4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate 在 palladium on activated charcoal 、 potassium tert-butylate 、 氢气 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 17.5h， 生成 methyl 4-((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)butanoate
  参考文献：
  名称：

  Synthesis of Bifunctional Lipoxin‐Derived Enzyme‐Triggered CO‐Releasing Molecules (LipET‐CORMs)

  摘要：

  AbstractIn an attempt to develop new anti‐inflammatory agents which act by co‐release of carbon monoxide (CO) and a specialized pro‐resolving mediator, we designed conjugates of a lipoxin A4 analogue and an acyloxycyclohexadiene‐Fe(CO)3 complex as an esterase‐triggered CO‐releasing molecule (ET‐CORM). After adjustment of the protecting group strategy, two of such compounds were successfully prepared by total synthesis (12 steps; 4–5 % overall yield) starting from deoxy‐d‐ribose and exploiting a Wittig olefination and an intermolecular Heck reaction as key C−C bond‐forming steps. A crucial late reduction of an aryl‐ketone moiety in the presence of a highly sensitive dienol ester functionality was achieved with BH3‐SMe2 in the presence of catalytic amounts of NaBH4. Both target compounds were dose‐dependently toxic towards cultured human umbilical vein endothelial cells (HUVEC), with LipET‐CORM 1‐A being slightly more toxic. While induction of heme oxygenase 1 (HO‐1) in HUVEC was observed for both compounds, they did not inhibit TNF‐α‐mediated VCAM‐1 expression in these cells. In M2 polarized macrophages HO‐1 expression was more pronounced as compared to M1 polarized macrophages. In both types of macrophages HO‐1 expression was downregulated by lipopolysaccharide, but only in M2 macrophages HO‐1 expression was rescued by LipET‐CORM. 15‐Lipoxygenase (15‐LO) was only expressed in M2 macrophages and was not influenced by LipET‐CORM. Collectively our data demonstrate that LipET‐CORMs induce HO‐1 expression in endothelial cells and M2 polarized macrophages. The role of the intra‐cellular released lipoxin A4 in resolution of inflammation, however, remains to be assessed.

  DOI：

  10.1002/ejoc.202201424

文献信息

• Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A₄Mimetics (QNX-sLXms)
  作者：Monica de Gaetano、Catherine Tighe、Kevin Gahan、Andrea Zanetti、Jianmin Chen、Justine Newson、Antonino Cacace、Mariam Marai、Andrew Gaffney、Eoin Brennan、Phillip Kantharidis、Mark E. Cooper、Xavier Leroy、Mauro Perretti、Derek Gilroy、Catherine Godson、Patrick J. Guiry

  DOI：10.1021/acs.jmedchem.1c00403

  日期：2021.7.8

  therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure–activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly

  未能解决炎症是许多普遍病理的基础。最近的研究发现，以脂氧素 (LXs) 为代表的脂质介质是炎症消退的驱动因素，表明具有潜在的治疗益处。我们报告了新型含喹喔啉的合成-LXA 4模拟物（QNX-sLXms）的不对称制备。筛选了八种新化合物对炎症反应的影响。构效关系 (SAR) 研究表明，( R )- 6（也称为 AT-02-CT）是所测试的化合物中最有效和最有效的抗炎化合物。(右)- 6显着减弱单核细胞和血管平滑肌细胞中脂多糖 (LPS) 和肿瘤坏死因子-α (TNF-α) 诱导的 NF-κB 活性。研究了( R ) -6的分子靶标。( R )- 6激活内源性 LX 受体甲酰肽受体 2 (ALX/FPR2)。的抗炎特性（[R ） - 6进一步研究在体内鼠模型中的急性炎症。与体外观察结果一致，( R )- 6减弱了炎症反应。这些结果支持先导 QNX-sLXm ( R )-6在新型炎症调节剂的背景下。
• ZrCl₄ as an Efficient Catalyst for a Novel One-Pot Protection/Deprotection Synthetic Methodology
  作者：Surendra Singh、Colm D. Duffy、Syed Tasadaque A. Shah、Patrick J. Guiry

  DOI：10.1021/jo800932t

  日期：2008.8.1

  found to be an efficient catalyst for the one-pot esterification and deprotection of (5S,6R)-5,6-diacetoxyoct-7-enoic acid in good yields (44−62%) with a lactone formed as a minor byproduct. ZrCl4 (10−20 mol %) was also sufficient to deprotect 1,3-dioxalane, bis-TBDMS ethers, and diacetate functional groups in excellent yields of up to 93%. ZrCl4 (1−10 mol %) also promoted diol protection as the acetonide

  发现催化量的ZrCl 4（20 mol％）是一种有效的催化剂，用于以高收率一锅法酯化和（5 S，6 R）-5,6-二乙酰氧基辛-7-烯酸脱保护（44 -62％），形成内酯为次要副产物。ZrCl 4（10-20 mol％）也足以以高达93％的优异收率对1,3-二氧杂戊环，bis-TBDMS醚和二乙酸酯官能团进行脱保护。ZrCl 4（1-10 mol％）还以90％的收率促进了作为丙酮化物的二醇保护作用，并充当了一系列酯的酯交换催化剂。
• Heterocyclic lipoxin analogs and uses thereof
  申请人：University College Dublin, National University of Ireland, Dublin

  公开号：US11161824B2

  公开（公告）日：2021-11-02

  The present invention relates to a compound of formula (I): wherein L is an optionally substituted heterocyclic group excluding unsubstituted monocyclic pyridine groups; wherein a is 0, 1 or 2; wherein R1 is H or with R2 is a bond; wherein R2 is an optionally substituted alkoxy or aryloxy group, or with R1 forms a bond; wherein R3 is an optionally substituted alkyl group; and wherein R4 is CH2, CMe2 or O. Such compounds may be used in the treatment or prophylaxis of a disease or condition in which inhibition of acute inflammation and/or promotion of its resolution and/or suppression of fibrosis.

  本发明涉及式(I)化合物：其中L为任选取代的杂环基团，不包括未取代的单环吡啶基团；其中a为0、1或2；其中R1为H或与R2为键；其中R2为任选取代的烷氧基或芳氧基，或与R1形成键；其中R3为任选取代的烷基；以及其中R4为CH2、CMe2或O。此类化合物可用于抑制急性炎症和/或促进炎症消退和/或抑制纤维化的疾病或病症的治疗或预防。
• HETEROCYCLIC LIPOXIN ANALOGS AND USES THEROF
  申请人：University College Dublin, National University of Ireland, Dublin

  公开号：EP3500559B1

  公开（公告）日：2021-06-16
• Heterocyclic Lipoxin Analogs and Uses Thereof
  申请人：University College Dublin

  公开号：US20210053927A1

  公开（公告）日：2021-02-25

  The present invention relates to a compound of formula (I): wherein L is an optionally substituted heterocyclic group excluding unsubstituted monocyclic pyridine groups; wherein a is 0, 1 or 2; wherein R 1 is H or with R 2 is a bond; wherein R 2 is an optionally substituted alkoxy or aryloxy group, or with R 1 forms a bond; wherein R 3 is an optionally substituted alkyl group; and wherein R 4 is CH 2 , CMe 2 or O. Such compounds may be used in the treatment or prophylaxis of a disease or condition in which inhibition of acute inflammation and/or promotion of its resolution and/or suppression of fibrosis.