(Z)-methyl 2-((S)-2-((R)-2-amino-3-methylbutanamido)-3-(tritylthio)propanamido)but-2-enoate | 1089192-69-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-methyl 2-((S)-2-((R)-2-amino-3-methylbutanamido)-3-(tritylthio)propanamido)but-2-enoate
• 英文别名: (Z)-2-[(S)-2-((R)-2-amino-3-methyl-butyrylamino)-3-tritylsulfanyl-propionylamino]-but-2-enoic acid methyl ester；H-D-Val-D-Cys(Trt)-Abu(2,3-dehydro)-OMe；methyl (Z)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-tritylsulfanylpropanoyl]amino]but-2-enoate
• CAS: 1089192-69-7
• 化学式: C₃₂H₃₇N₃O₄S
• 分子量: 559.729
• InChiKey: SUCWNUTXRIWIJB-MCPUIODLSA-N

物化性质

• 沸点：
  759.3±60.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (Z)-methyl 2-((S)-2-((R)-2-amino-3-methylbutanamido)-3-(tritylthio)propanamido)but-2-enoate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 生成
  参考文献：
  名称：

  Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor

  摘要：

  The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.

  DOI：

  10.1021/jo801866z
• 作为产物：
  描述：

  Fmoc-D-缬氨酸 在 三乙烯二胺 作用下， 以 二氯甲烷 为溶剂， 反应 11.17h， 生成 (Z)-methyl 2-((S)-2-((R)-2-amino-3-methylbutanamido)-3-(tritylthio)propanamido)but-2-enoate
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ETHYLIDENE-4,21-BIS(1-METHYLETHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TETRAAZABICYCLO[8.7.6]TRICOS-16-ENE-3, 6, 9, 19, 22-PENTONE
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ÉTHYLIDÈNE-4,21-BIS(1-MÉTHYLÉTHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TÉTRAAZABICYCLO[8.7.6]TRICOS-16-ÈNE-3, 6, 9, 19, 22-PENTONE

  摘要：

  本发明涉及一种改进的制备过程，用于制备式I的(1S,4S,7Z,10S,16E,21R)-7-乙烯基-4,21-双(1-甲基乙基)-2-氧-12,13-二硫-5,8,20,23-四氮杂环[8.7.6]三十一烯-16-烯-3,6,9,19,22-五酮。

  公开号：

  WO2017068596A1

文献信息

• Process for the preparation of (1S, 4S, 7Z, 10S, 16E, 21R)-7-ethyldene-4,21-bis(1-methyl-ethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3, 6, 9, 19, 22-pentone
  申请人：Rajan Srinivasan Thirumalai

  公开号：US10562931B2

  公开（公告）日：2020-02-18

  The present invention is relates to an improved process for the preparation (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabi-cyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone of formula I.

  本发明涉及一种制备式 I 的(1S,4S,7Z,10S,16E,21R)-7-亚乙基-4,21-双(1-甲基乙基)-2-氧杂-12,13-二硫杂-5,8,20,23-四氮杂双环[8.7.6]三os-16-烯-3,6,9,19,22-戊酮的改进工艺。
• AN IMPROVED PROCESS FOR THE PREPARATION OF (1S, 4S, 7Z, 10S, 16E, 21R)-7-ETHYLDENE-4,21-BIS(1-METHYL-ETHYL)-2-OXA-12,13-DITHIA-5,8,20,23-TETRAAZABICYCLO [8.7.6]TRICOS-16-ENE-3, 6, 9, 19, 22-PENTONE
  申请人：MSN LABORATORIES PRIVATE LIMITED

  公开号：US20180312538A1

  公开（公告）日：2018-11-01

  The present invention is relates to an improved process for the preparation (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabi-cyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone of formula I.
• Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor
  作者：Shijun Wen、Graham Packham、A. Ganesan

  DOI：10.1021/jo801866z

  日期：2008.12.5

  The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ETHYLIDENE-4,21-BIS(1-METHYLETHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TETRAAZABICYCLO[8.7.6]TRICOS-16-ENE-3, 6, 9, 19, 22-PENTONE<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ÉTHYLIDÈNE-4,21-BIS(1-MÉTHYLÉTHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TÉTRAAZABICYCLO[8.7.6]TRICOS-16-ÈNE-3, 6, 9, 19, 22-PENTONE
  申请人：MSN LABORATORIES PRIVATE LTD

  公开号：WO2017068596A1

  公开（公告）日：2017-04-27

  The present invention is relates to an improved process for the preparation (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabi-cyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone of formula I.

  本发明涉及一种改进的制备过程，用于制备式I的(1S,4S,7Z,10S,16E,21R)-7-乙烯基-4,21-双(1-甲基乙基)-2-氧-12,13-二硫-5,8,20,23-四氮杂环[8.7.6]三十一烯-16-烯-3,6,9,19,22-五酮。