tert-butyl (1R,9S)-4,7,9-tribromo-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-methyl-3,6-dioxo-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-16-carboxylate | 1219135-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl (1R,9S)-4,7,9-tribromo-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-methyl-3,6-dioxo-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-16-carboxylate
• CAS: 1219135-49-5
• 化学式: C₂₆H₃₆Br₃N₃O₅Si
• 分子量: 738.386
• InChiKey: OSZBJKLTJJGCFI-NJHUVSBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.27
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,9S)-4,7,9-tribromo-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-methyl-3,6-dioxo-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-16-carboxylate 在 cobalt,triphenylphosphane,chloride 、 三氟化硼乙醚 、 硫化氢 、 水 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 6.0h， 生成 (1R,4S,7S,9R)-4-(hydroxymethyl)-9-[(1R,4S,7S,9R)-4-(hydroxymethyl)-5-methyl-3,6-dioxo-4,7-bis(sulfanyl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-trien-9-yl]-5-methyl-4,7-bis(sulfanyl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione
  参考文献：
  名称：

  Total syntheses of chaetocin and ent-chaetocin

  摘要：

  The first total synthesis of chaetocin (1), a potent histone methyltransferase inhibitor, is described in detail. Key reactions were radical bromination for alpha-oxidation of the diketopiperazine ring, and reductive radical coupling for construction of the dimeric core structure. Stereoselective construction of the disulfide bridges was achieved via substitution reaction with H2S. The total synthesis of 1 was accomplished in nine steps starting from known D-amino acid derivatives. Total synthesis of non-natural ent-chaetocin (ent-1) was also achieved via the established synthetic route, starting from.-amino acid derivatives. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.081
• 作为产物：
  描述：

  methyl N-((benzyloxy)carbonyl)-N-methyl-D-seryl-D-tryptophanate 在 咪唑 、 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二甲氧基异庚腈 、 palladium 10% on activated carbon 、 氨 、 氢气 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 84.0h， 生成 tert-butyl (1R,9S)-4,7,9-tribromo-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-methyl-3,6-dioxo-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-16-carboxylate
  参考文献：
  名称：

  Total syntheses of chaetocin and ent-chaetocin

  摘要：

  The first total synthesis of chaetocin (1), a potent histone methyltransferase inhibitor, is described in detail. Key reactions were radical bromination for alpha-oxidation of the diketopiperazine ring, and reductive radical coupling for construction of the dimeric core structure. Stereoselective construction of the disulfide bridges was achieved via substitution reaction with H2S. The total synthesis of 1 was accomplished in nine steps starting from known D-amino acid derivatives. Total synthesis of non-natural ent-chaetocin (ent-1) was also achieved via the established synthetic route, starting from.-amino acid derivatives. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.081

文献信息

• Total Synthesis of (+)-Chaetocin and its Analogues: Their Histone Methyltransferase G9a Inhibitory Activity
  作者：Eriko Iwasa、Yoshitaka Hamashima、Shinya Fujishiro、Eisuke Higuchi、Akihiro Ito、Minoru Yoshida、Mikiko Sodeoka

  DOI：10.1021/ja101280p

  日期：2010.3.31

  The first total synthesis of (+)-chaetocin has been accomplished in nine steps starting from known N-Cbz-N-Me-serine using radical alpha-bromination reaction of diketopiperazine 10 and Co(I)-mediated reductive dimerization reaction of 12 as key reactions. The enantiomers show comparable inhibitory activity toward histone methyltransferase (HMT) G9a, but analogues without the sulfur functionality are inactive.