(+)-(R)-12,14-dimethoxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclododecin-1-one | 125590-95-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (+)-(R)-12,14-dimethoxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclododecin-1-one
• 英文别名: (R)-(+)-2,4-dimethoxy-7-methyl-7,8,9,10,11,12,13,14-octahydro-6-oxa-benzocyclododecane-5-one；(R)-12,14-dimethoxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclododecin-1-one；methyl-(R)-(+)-lasiodiplodin；(+)(R) methyl lasiodiplodin；(R)-4-Methyllasiodiplodin；(R)-(+)-lasiodiplodin methyl ether；(4R)-14,16-dimethoxy-4-methyl-3-oxabicyclo[10.4.0]hexadeca-1(12),13,15-trien-2-one
• CAS: 125590-95-6
• 化学式: C₁₈H₂₆O₄
• 分子量: 306.402
• InChiKey: TUQSBFVIDALSBD-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 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：

  (+)-(R)-12,14-dimethoxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclododecin-1-one 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 4.33h， 生成
  参考文献：
  名称：

  Synthesis, modification, and evaluation of (R)-de-O-methyllasiodiplodin and analogs as nonsteroidal antagonists of mineralocorticoid receptor

  摘要：

  Macrolide (R)-de-O-methyllasiodiplodin (1), discovered to be a potent nonsteroidal antagonist of the mineralocorticoid receptor (MR), was synthesized via an efficient method and evaluated for MR antagonistic activity together with its analogs. Among all the tested compounds, compounds 18a, 18b and 18c, exhibited more potent antagonistic activity against MR with IC50 values ranging from 0.58 to 1.11 mu M. Generally, it was obviously demonstrated that acetylation at phenolic hydroxyl groups and the ring size in analogs of 1 were very important for MR antagonist activity. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.101
• 作为产物：
  描述：

  methyl 2,4-dimethoxy-6-<(phenylthio) methyl>-benzoate 在 氢氧化钾 、 2,2'-二硫二吡啶 、 四丁基氟化铵 、 水 、 silver perchlorate 、 镍 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 乙二醇 为溶剂， 反应 48.5h， 生成 (+)-(R)-12,14-dimethoxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclododecin-1-one
  参考文献：
  名称：

  Catalytic enantioselective synthesis of macrolides via asymmetric alkylation

  摘要：

  Catalytic enantioselective syntheses of the macrolides (R)-(-) phoracantholide and (R)-(+) lasiodiplodin have been achieved. Stereochemistry was introduced in using an arene chromium tricarbonyl derived catalyst, which mediated the enantioselective addition of dimethyl zinc to a functionalized aldehyde. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(97)00186-9

文献信息

• Macrocycles by ring-closing-metathesis, XI: Syntheses of (R)-(+)-lasiodiplodin, zeranol and truncated salicylihalamides
  作者：Alois Fürstner、Günter Seidel、Nicole Kindler

  DOI：10.1016/s0040-4020(99)00302-6

  日期：1999.7

  Concise, flexible and high yielding approaches to the orsellinic acid type macrolides lasiodiplodin 1 and zeranol 3 are described which involve only metal-assisted or metal-catalyzed CC-bond formations. Key steps are the efficient allylation of aryl triflates 14 and 25 either by Stille or by modified Suzuki coupling reactions, and the high yielding ring closure of the macrocyclic rings by RCM using

  描述了一种简单，灵活且高产的方法，以奥数酸为基础的大环内酯类拉索二倍体1和麦角醇3仅涉及金属辅助或金属催化的CC键形成。关键步骤是通过Stille或通过改进的Suzuki偶联反应有效地芳基三氟甲磺酸酯14和25烯丙基化，以及使用钌卡宾18作为催化剂通过RCM高效合成大环的环。合成中间体之一，即环烯烃16，也可以视为有效的抗肿瘤剂水杨酰卤酰胺A 7的截短类似物。从16的体外细胞毒性数据，可以推断出水杨酰卤酰胺的结构/活性关系的初步见解。
• Formal Synthesis of (R)-(+)-Lasiodiplodin
  作者：Adriaan Minnaard、Ben Feringa、Yange Huang

  DOI：10.1055/s-0030-1258453

  日期：2011.4

  A catalytic approach is reported for the enantioselective synthesis of (R)-(+)-lasiodiplodin methyl ether using asymmetric hetero allylic alkylation as the key step. formal synthesis - lasiodiplodin - asymmetric allylic alkylation - Suzuki coupling - ring-closing metathesis

  据报道，使用不对称杂烯丙基烷基化作为关键步骤，对映体选择性合成（R）-（+）-Lasiodiplodin甲醚的催化方法。 形式合成-拉西地普定-不对称烯丙基烷基化-铃木偶联-闭环复分解
• Asymmetric synthesis of orsellinic acid type macrolides: The example of lasiodiplodin
  作者：Guy Solladié、Almudena Rubio、M.Carmen Carreño、JoséL. García Ruano

  DOI：10.1016/0957-4166(90)90013-z

  日期：1990.1

  The asymmetric synthesis of both enantiomers of methyl lasiodiplodin is described. The chiral centers were created in the very last steps of the synthesis by asymmetric induction of a chiral sulfoxide group.

  描述了甲基拉西地夫定的两种对映异构体的不对称合成。手性中心是在合成的最后步骤中通过不对称诱导手性亚砜基而产生的。
• Chemoenzymatic Asymmetric Total Synthesis of (<i>R</i>)-Lasiodiplodin Methyl Ether through a Sulfatase-Based Deracemization Process
  作者：Michael Fuchs、Michael Toesch、Markus Schober、Christiane Wuensch、Kurt Faber

  DOI：10.1002/ejoc.201201296

  日期：2013.1

  lasiodiplodin, was synthesized through a seven-step linear sequence. Chirality was introduced through a sulfatase-based deracemization process, in which a functionalized (rac)-sec-sulfate ester was enzymatically hydrolyzed with inversion of the stereocenter using an alkyl sulfatase. The remaining sulfate ester enantiomer was hydrolyzed with retention of configuration under acidic conditions, yielding the chiral

  (R)-Lasiodiplodin 甲基醚是抗白血病药物 lasiodiplodin 的前体，通过七步线性序列合成。手性是通过基于硫酸酯酶的去外消旋过程引入的，其中使用烷基硫酸酯酶对功能化的 (外消旋)-仲硫酸酯进行酶水解，立体中心反转。剩余的硫酸酯对映体在酸性条件下水解并保留构型，以 93% ee 得到手性关键构件作为唯一产物。全合成通过 Negishi 交叉偶联和闭环复分解完成。
• Macrocycle formation by ring-closing-metathesis. 2. An efficient synthesis of enantiomerically pure (R)-(+)-lasiodiplodin
  作者：Alois Fürstner、Nicole Kindler

  DOI：10.1016/0040-4039(96)01590-0

  日期：1996.9

  A highly efficient and flexible route to the macrolide (R)-(+)-lasiodiplodin 1 and its de-O-methyl congener 2 is outlined, which is based on the formation of the 12-membered ring by ring-closing metathesis (RCM) as the key step.

  概述了通向大环内酯（R）-（+）-lasiodiplodin 1及其脱-O-甲基同类物2的高效且灵活的路线，该路线基于通过闭环易位反应（RCM）形成的12元环）作为关键步骤。