methyl 4-((4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate | 76745-14-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 4-((4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate
• CAS: 76745-14-7
• 化学式: C₁₁H₁₈O₅
• 分子量: 230.261
• InChiKey: LUVYDJKRPIDKII-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.62
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  64.99
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 4-((4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate 在 咪唑 、 甲醇 、 sodium tetrahydroborate 、 三正丁胺 、 palladium on activated charcoal 、 potassium tert-butylate 、 氢气 、 palladium diacetate 、 戴斯-马丁氧化剂 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 methyl 4-((4S,5R)-5-((E)-2-(1-((tert-butyldimethylsilyl)oxy)hexyl)styryl)-2,2-dimethyl-1,3-dioxolane-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
• 作为产物：
  描述：

  2-deoxy-D-ribose 在 4-甲基苯磺酸吡啶 、 苯甲酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成 methyl 4-((4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate
  参考文献：
  名称：

  含咪唑和恶唑的合成脂质体A 4模拟物（sLXms）的不对称合成和生物学评估

  摘要：

  脂蛋白（LX）是内源性类花生酸，具有有效的生物作用，与炎症减轻一致。LXs昂贵的合成和代谢不稳定性可能会限制其治疗潜力。在这里，我们报告合成和表征新型咪唑/含恶唑的合成LX模拟物（sLXms）。假定的sLXms不对称合成的关键步骤包括Suzuki反应和不对称酮还原。使用稳定表达核因子Kappa B（NF kB）通过研究下游细胞因子的分泌来报道基因。咪唑的潜在相互作用/与LXS的分子靶恶唑，即G蛋白偶联受体（GPCR）甲酰肽受体2（ALX / FPR2）使用其中ALX / FPR2耦合到Gα一个电池系统研究q亚单位和受体相互作用是通过细胞内钙的动员来确定的。使用小鼠酵母聚糖诱导的腹膜炎模型评估了体内抗炎作用。总体而言，结构-活性关系（SAR）研究表明6C-二甲基咪唑（1R）-11的（R）受体在所测试的十种化合物中，它是最有效，最有效的消炎药。该分子在体内显着减弱了LPS诱导的NFkB活性，减

  DOI：

  10.1016/j.ejmech.2018.10.049

文献信息

• Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution, development, and application of a catalytic dipolar cycloaddition cascade
  作者：Charles S. Shanahan、Chao Fang、Daniel H. Paull、Stephen F. Martin

  DOI：10.1016/j.tet.2013.03.104

  日期：2013.9

  operation from an acyclic precursor. The key step in the synthesis is a novel dipolar cycloaddition cascade sequence that is initiated by cyclization of a rhodium-derived carbene onto the nitrogen atom of a proximal imine group to generate an azomethine ylide that then undergoes spontaneous cyclization via dipolar cycloaddition. The synthesis features several other interesting reactions, including a Boord

  通过从市售的 2-脱氧-d制备这些生物碱的 Overman 合成中的中间体，已经完成了双脱氢 Stemofoline 和 isodidehydrostemofoline 的正式合成。-核糖。本报告中介绍的工作记录了我们探索的演变，以确定在从无环前体的单个操作中生成这些生物碱的三环核心结构所需的最佳空间和电子控制元素。合成中的关键步骤是一种新型偶极环加成级联序列，该序列通过将铑衍生的卡宾环化到近端亚胺基团的氮原子上以生成偶氮甲碱叶立德，然后通过偶极环加成进行自发环化而引发。该合成具有其他几个有趣的反应，包括用于制备手性烯丙醇的 Boord 消除、高度非对映选择性的 Hirama-Itô 环化，以及对 Barton 脱羧方案的有用修改。
• Synthesis of an electrophilic keto-tetraene 15-oxo-Lipoxin A4 methyl ester via a MIDA boronate
  作者：Steven R. Woodcock、Stacy G. Wendell、Francisco J. Schopfer、Bruce A. Freeman

  DOI：10.1016/j.tetlet.2018.08.014

  日期：2018.9

  (15-oxo-LXA4) has been identified as a natural metabolite of the fatty acid signaling mediator Lipoxin A4. Herein, we report a total synthesis of the methyl ester of 15-oxo-LXA4 to be used in investigations of potential electrophilic bioactivity of this metabolite. The methyl ester of 15-oxo-LXA4 was synthesized in a convergent 15 step (9 steps longest linear) sequence starting from 1-octyn-3-ol and 2-deoxy-d-ribose

  15-oxo-Lipoxin A 4 (15-oxo-LXA 4 ) 已被鉴定为脂肪酸信号传导介质 Lipoxin A 4的天然代谢物。在此，我们报告了 15-氧代-LXA 4甲酯的全合成，用于研究该代谢物的潜在亲电生物活性。15-oxo-LXA 4的甲酯是在收敛的 15 步（最长 9 步线性）序列中合成的，从 1-octyn-3-ol 和 2- deoxy- d-核糖开始，Sonogashira 和 Suzuki 交叉偶联MIDA硼酸盐作为关键步骤。
• Synthesis and Biological Evaluation of Bicyclo[1.1.1]pentane-Containing Aromatic Lipoxin A₄ Analogues
  作者：Benjamin Owen、Monica de Gaetano、Andrew Gaffney、Catherine Godson、Patrick J. Guiry

  DOI：10.1021/acs.orglett.2c02345

  日期：2022.8.19

  Bicyclo[1.1.1]pentanes (BCPs) are potential isosteric replacements for arenes and/or alkyl groups within drug candidates. We carried out an asymmetric synthesis of four BCP-containing synthetic lipoxin A4 mimetics (BCP-sLXms) in which the key steps were a Suzuki coupling, an asymmetric ketone reduction, and a triethylborane-initiated radical bicyclopentylation. These mimetics were screened for their impact

  脂氧素是炎症消退的重要驱动因素，表明潜在的治疗益处。双环[1.1.1]戊烷 (BCP) 是候选药物中芳烃和/或烷基的潜在等排替代品。我们对四种含有 BCP 的合成脂氧素 A 4模拟物 (BCP-sLXms)进行了不对称合成，其中关键步骤是 Suzuki 偶联、不对称酮还原和三乙基硼烷引发的自由基双环戊基化。筛选了这些模拟物对炎症反应的影响，发现一种咪唑-BCP-sLXm ( 6a ) 具有高抗炎活性。
• Leukotriene B. Total synthesis and assignment of stereochemistry
  作者：E. J. Corey、Anthony Marfat、Giichi Goto、Francis Brion

  DOI：10.1021/ja00547a051

  日期：1980.12