N-(2S,3R,4'S)-(3-hydroxy-2-methylhexadecanoyl)-4'-isopropyl-3-propionyloxazolidin-2'-one | 452956-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: N-(2S,3R,4'S)-(3-hydroxy-2-methylhexadecanoyl)-4'-isopropyl-3-propionyloxazolidin-2'-one
• 英文别名: (4S)-3-[(2S,3R)-3-hydroxy-2-methylhexadecanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 452956-77-3
• 化学式: C₂₃H₄₃NO₄
• 分子量: 397.599
• InChiKey: SHXWQEQLVFKURZ-PWRODBHTSA-N

物化性质

• 沸点：
  523.2±33.0 °C(Predicted)
• 密度：
  1.002±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  28
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2S,3R,4'S)-(3-hydroxy-2-methylhexadecanoyl)-4'-isopropyl-3-propionyloxazolidin-2'-one 在 吡啶 、 咪唑 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 copper(l) iodide 、 锂硼氢 、 草酰氯 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 二异丁基氢化铝 、 二甲基亚砜 、 (-)-diethyl tartrate 、 三乙胺 作用下， 以 四氢呋喃 、 癸烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 151.67h， 生成 (2S,3R)-2-((4S,5S)-2,2,5-Trimethyl-[1,3]dioxan-4-yl)-hexadecan-3-ol
  参考文献：
  名称：

  Stevastelins的合成研究。1. Stevastelins B和B3的全合成

  摘要：

  描述了stevastelin B3（2）和B（5）的合成。在第一种方法中，环氧环二肽8被认为是合成Stevastelins的[15]元环成员的有前途的候选者。然而，完成天然stevastelin合成所需的环氧乙烷开环失败。因此，我们合成了stevastelin B（5），在合成过程中较早地进行了环氧乙烷开环，并遵循了能够递送类似物的合成方案。另一方面，[15]成员环衍生物59的内酯化反应导致合成了stevastelins家族的天然[13]成员环成分stevastelin B3（2）。

  DOI：

  10.1021/jo050625l
• 作为产物：
  描述：

  肉豆蔻醛 、 (S)-4-异丙基-3-丙酰基-2-恶唑烷酮 在 三氟甲磺酸二丁硼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 以85%的产率得到N-(2S,3R,4'S)-(3-hydroxy-2-methylhexadecanoyl)-4'-isopropyl-3-propionyloxazolidin-2'-one
  参考文献：
  名称：

  Stevastelins的合成研究。1. Stevastelins B和B3的全合成

  摘要：

  描述了stevastelin B3（2）和B（5）的合成。在第一种方法中，环氧环二肽8被认为是合成Stevastelins的[15]元环成员的有前途的候选者。然而，完成天然stevastelin合成所需的环氧乙烷开环失败。因此，我们合成了stevastelin B（5），在合成过程中较早地进行了环氧乙烷开环，并遵循了能够递送类似物的合成方案。另一方面，[15]成员环衍生物59的内酯化反应导致合成了stevastelins家族的天然[13]成员环成分stevastelin B3（2）。

  DOI：

  10.1021/jo050625l

文献信息

• Total Synthesis of Stevastelin B, a Novel Immunosuppressant
  作者：Naoki Kohyama、Yukio Yamamoto

  DOI：10.1055/s-2001-13382

  日期：——

  Total synthesis of stevastelin B is described. Evans asymmetric aldol methodology and Roush asymmetric allylation were used to construct four consecutive stereo-centers on the octadecanoic acid moiety of stevastelin B. Subsequent coupling with a dipeptide and macrolactamization gave stevastelin B. The flexibility of this route could allow the synthesis of many analogues for biological tests, which cannot be obtained from natural sources.

  本文介绍了甜叶菊苷 B 的全合成。利用伊文思不对称醛醇法和鲁什不对称烯丙基化法在十八烷酸分子上构建了四个连续的立体中心。
• A macrolactonization approach to the stevastelins
  作者：Francisco Sarabia、Samy Chammaa、F.Jorge López-Herrera

  DOI：10.1016/s0040-4039(02)00416-1

  日期：2002.4

  A synthesis of the stevastelins. a novel class of immunosuppressant agents, is reported based on a macrolactonization approach. This synthesis commenced with the stereoselective preparation of the stearic acid segment from tetradecanal using Evans asymmetric synthesis methodology and an aldol reaction with a thioester. After a high yielding coupling reaction between the fatty acid residue and the corresponding tripeptide. we proceeded with the macrolactonization key step. Thus, macrolactonizations of hydroxy acid 27 and dihydroxy acid 30, according to Yamaguchi conditions, afforded the corresponding 13-membered ring stevastelin derivatives 28 and 31 in 90 and 82% yields, respectively. In this latter case, the corresponding 15-membered lactone was not formed. Finally. depsipeptide derivative 31 was converted into stevastelin C3 (5). (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthetic Studies on Stevastelins. 1. Total Synthesis of Stevastelins B and B3
  作者：Francisco Sarabia、Samy Chammaa

  DOI：10.1021/jo050625l

  日期：2005.9.1

  The synthesis of stevastelin B3 (2) and B (5) are described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a promising candidate for the synthesis of the [15]-membered ring members of the stevastelins; however, the oxirane ring opening, required for the completion of the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B (5), carrying out the oxirane ring opening

  描述了stevastelin B3（2）和B（5）的合成。在第一种方法中，环氧环二肽8被认为是合成Stevastelins的[15]元环成员的有前途的候选者。然而，完成天然stevastelin合成所需的环氧乙烷开环失败。因此，我们合成了stevastelin B（5），在合成过程中较早地进行了环氧乙烷开环，并遵循了能够递送类似物的合成方案。另一方面，[15]成员环衍生物59的内酯化反应导致合成了stevastelins家族的天然[13]成员环成分stevastelin B3（2）。
• Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors
  作者：Andrew J. Carnell、Ian Hale、Simone Denis、Ronald J. A. Wanders、William B. Isaacs、Brice A. Wilson、Sacha Ferdinandusse

  DOI：10.1021/jm0702377

  日期：2007.5.1

  The enzyme alpha-methylacyl-CoA racemase (AMACR) is overexpressed in prostate, colon, and other cancers and has been partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene. Analogs of the natural substrate branched chain alpha-methylacyl coenzyme A esters, possessing one or more beta-fluorine atoms, have been synthesized using Wittig, conjugate addition, and asymmetric aldol reactions and found to be reversible competitive inhibitors. Each diastereomer of the previously reported inhibitor ibuprofenoyl-CoA was also tested. The compounds had K-i values of 0.9-20 mu M and are the most potent inhibitors yet known. The presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the K-i value compared with nonfluorinated analogs, and this is attributed to a lowering of the pK(a) of the alpha-proton, facilitating enolization and binding. Several of the CoA ester inhibitors were formed by incubating the free carboxylic acid precursors with cell free extracts and CoA. alpha-Trifluoromethyltetradecanoic acid, the precursor to the most potent inhibitor, was shown to inhibit growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner and could be related to the expression level of AMACR.