(3R,5S)-3-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-one | 1240507-80-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3R,5S)-3-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-one
• CAS: 1240507-80-5
• 化学式: C₁₁H₂₂O₄Si
• 分子量: 246.379
• InChiKey: FUTTVBGDYDWSFB-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.68
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,5S)-3-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-one 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以60%的产率得到(2R,4S)-2-hydroxy-4-hydroxymethyl-4-butanolide
  参考文献：
  名称：

  Destruxin E的合成，结构测定和生物学评估

  摘要：

  首次获得了destruxin E（1）的全合成，并且其手性中心在环氧化物上的立体化学被确定为（S）。通过固相肽合成来合成环化前体3a。利用MNBA- DMAPO对3a进行大分子内酯化，然后形成环氧化物，然后得到destruxinE 。其非对映异构体Epi- destruxin E（2）也以相同的方式合成。此外，生物学评估表明，destruxin E的V-ATPase抑制活性比Epi- destruxin E的高10倍。

  DOI：

  10.1021/ol101449x
• 作为产物：
  描述：

  (R)-2-(tert-butyldimethylsilyloxy)pent-4-enoic acid methyl ester 在 2O₆Os^(2-)*2K⁽¹⁺⁾ 、 potassium carbonate 、 氢化奎尼定 1,4-(2,3-二氮杂萘)二醚 、 potassium hexacyanoferrate(III) 作用下， 以 水 、 叔丁醇 为溶剂， 以18%的产率得到
  参考文献：
  名称：

  Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology

  摘要：

  The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)(2)PHAL as the chiral ligand, and it was found that the use of the L-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).

  DOI：

  10.1021/jo402437z

文献信息

• Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology
  作者：Masahito Yoshida、Hiroshi Sato、Yoshitaka Ishida、Hiroshi Nakagawa、Takayuki Doi

  DOI：10.1021/jo402437z

  日期：2014.1.3

  The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)(2)PHAL as the chiral ligand, and it was found that the use of the L-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).
• Synthesis, Structure Determination, and Biological Evaluation of Destruxin E
  作者：Masahito Yoshida、Hisayuki Takeuchi、Yoshitaka Ishida、Yoko Yashiroda、Minoru Yoshida、Motoki Takagi、Kazuo Shin-ya、Takayuki Doi

  DOI：10.1021/ol101449x

  日期：2010.9.3

  The total synthesis of destruxin E (1) has been achieved for the first time, and the stereochemistry of its chiral center at the epoxide has been determined to be (S). The cyclization precursor 3a was synthesized by solid-phase peptide synthesis. Macrolactonization of 3a utilizing MNBA-DMAPO, followed by formation of the epoxide, then furnished destruxin E. Its diastereomer, epi-destruxin E (2), was

  首次获得了destruxin E（1）的全合成，并且其手性中心在环氧化物上的立体化学被确定为（S）。通过固相肽合成来合成环化前体3a。利用MNBA- DMAPO对3a进行大分子内酯化，然后形成环氧化物，然后得到destruxinE 。其非对映异构体Epi- destruxin E（2）也以相同的方式合成。此外，生物学评估表明，destruxin E的V-ATPase抑制活性比Epi- destruxin E的高10倍。