2(R,S)-hydroxy-3(S)-<(phenylmethoxycarbonyl)amino>-6-<<<(tert-butyloxycarbonyl)imino><(tert-butyloxycarbonyl)amino>methyl>amino>hexanoic acid | 190203-17-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2(R,S)-hydroxy-3(S)-<(phenylmethoxycarbonyl)amino>-6-<<<(tert-butyloxycarbonyl)imino><(tert-butyloxycarbonyl)amino>methyl>amino>hexanoic acid
• 英文别名: 2(R,S)-hydroxy-3(S)-[(phenylmethoxycarbonyl)amino]-6-({[(tert-butyloxycarbonyl)imino][(tert-butyloxycarbonyl)amino]methyl}amino)hexanoic acid
• CAS: 190203-17-9
• 化学式: C₂₅H₃₈N₄O₉
• 分子量: 538.598
• InChiKey: XMOGIWCLVDGJOY-ZENAZSQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  184.88
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2(R,S)-hydroxy-3(S)-<(phenylmethoxycarbonyl)amino>-6-<<<(tert-butyloxycarbonyl)imino><(tert-butyloxycarbonyl)amino>methyl>amino>hexanoic acid 在 palladium on activated charcoal 吗啉 、 4-二甲氨基吡啶 、 lithium hydroxide 、 四(三苯基膦)钯 、 茴香硫醚 、 氢气 、 silica gel 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 80.45h， 生成 cyclotheonamide B
  参考文献：
  名称：

  Flexible and Convergent Total Synthesis of Cyclotheonamide B

  摘要：

  A convergent approach using two key intermediates, segment A [a L-proline-L-alpha-hydroxy-beta-homoarginine-D-phenylalanine (Pro-hArg-D-Phe) tripeptide] and segment B [a vinylogous L-tyrosine-L-2,3-diaminopropanoic acid (vTyr-Dpr) dipeptide], was developed for the synthesis of cyclotheonamide B (Scheme 1). The starting compound for the preparation of the hArg moiety 7, the predominant part of segment A, was N-alpha-(benzyloxycarbonyl)-N-omega , N(omega)'bis(tert-butyloxycarbonyl)-l-arginine methyl ester (15, Scheme 2), which was converted into the aldehyde 16 and subsequently homologated using [tris(methylthio)methyl]lithium as a carboxylic acid anion equivalent. Coupling with properly protected Pro and D-Phe derivatives gave smoothly the desired Pro-hArg-D-Phe tripeptide derivative 24. The key feature of segment B, i.e., the L-tyrosine-derived alpha,beta-unsaturated gamma-amino acid 4, was prepared by a Wadsworth-Emmons olefination of the aldehyde 29 (Scheme 3) derived from N-(tert-butyloxycarbonyl), O-tert-butyl-L-tyrosine methyl ester (28). Selective N-(tert-butyloxycarbonyl) removal in the presence of the aryl tert-butyl ether present in the fully protected segment B, i.e., 32, was achieved by treatment with trimethylsilyl triflate/2,6-lutidine to give vTyr-Dpr dipeptide derivative 34 in quantitative yield. Coupling of the key intermediates 24 and 34 using 2-(1H-benzotriazol-l-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) afforded the protected linear pentapeptide 35 in high yield (Scheme 4). Treatment of 35 with Pd(PPh3)(4)/morpholine resulted in simultaneous removal of the C-terminal allyl group and the N-terminal allyloxycarbonyl group to yield 36. Ring closure was effected under dilution conditions by treatment with TBTU/1-hydroxybenzotriazole/4-(dimethylamino and gave the protected cyclopentapeptide 37 in 61% yield. Oxidation of the hydroxyl group with Dess-Rlartin periodinane (24 h, 40 degrees C) in the presence of tert-butyl alcohol gave 38, which was then subjected to O,N-deprotection with trifluoroacetic acid/thioanisole. Subsequent HPLC purification afforded cyclotheonamide B in an overall yield of 1.8% in 17 steps.

  DOI：

  10.1021/jo961447m
• 作为产物：
  描述：

  N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine 在 copper(II) carbonate 、 lithium hydroxide 、 正丁基锂 、 乙二胺四乙酸 、 二异丁基氢化铝 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 mercury dichloride 、 mercury(II) oxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 120.78h， 生成 2(R,S)-hydroxy-3(S)-<(phenylmethoxycarbonyl)amino>-6-<<<(tert-butyloxycarbonyl)imino><(tert-butyloxycarbonyl)amino>methyl>amino>hexanoic acid
  参考文献：
  名称：

  Flexible and Convergent Total Synthesis of Cyclotheonamide B

  摘要：

  A convergent approach using two key intermediates, segment A [a L-proline-L-alpha-hydroxy-beta-homoarginine-D-phenylalanine (Pro-hArg-D-Phe) tripeptide] and segment B [a vinylogous L-tyrosine-L-2,3-diaminopropanoic acid (vTyr-Dpr) dipeptide], was developed for the synthesis of cyclotheonamide B (Scheme 1). The starting compound for the preparation of the hArg moiety 7, the predominant part of segment A, was N-alpha-(benzyloxycarbonyl)-N-omega , N(omega)'bis(tert-butyloxycarbonyl)-l-arginine methyl ester (15, Scheme 2), which was converted into the aldehyde 16 and subsequently homologated using [tris(methylthio)methyl]lithium as a carboxylic acid anion equivalent. Coupling with properly protected Pro and D-Phe derivatives gave smoothly the desired Pro-hArg-D-Phe tripeptide derivative 24. The key feature of segment B, i.e., the L-tyrosine-derived alpha,beta-unsaturated gamma-amino acid 4, was prepared by a Wadsworth-Emmons olefination of the aldehyde 29 (Scheme 3) derived from N-(tert-butyloxycarbonyl), O-tert-butyl-L-tyrosine methyl ester (28). Selective N-(tert-butyloxycarbonyl) removal in the presence of the aryl tert-butyl ether present in the fully protected segment B, i.e., 32, was achieved by treatment with trimethylsilyl triflate/2,6-lutidine to give vTyr-Dpr dipeptide derivative 34 in quantitative yield. Coupling of the key intermediates 24 and 34 using 2-(1H-benzotriazol-l-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) afforded the protected linear pentapeptide 35 in high yield (Scheme 4). Treatment of 35 with Pd(PPh3)(4)/morpholine resulted in simultaneous removal of the C-terminal allyl group and the N-terminal allyloxycarbonyl group to yield 36. Ring closure was effected under dilution conditions by treatment with TBTU/1-hydroxybenzotriazole/4-(dimethylamino and gave the protected cyclopentapeptide 37 in 61% yield. Oxidation of the hydroxyl group with Dess-Rlartin periodinane (24 h, 40 degrees C) in the presence of tert-butyl alcohol gave 38, which was then subjected to O,N-deprotection with trifluoroacetic acid/thioanisole. Subsequent HPLC purification afforded cyclotheonamide B in an overall yield of 1.8% in 17 steps.

  DOI：

  10.1021/jo961447m

文献信息

• Total Synthesis of Cyclotheonamide B, a Facile Route towards Analogues
  作者：H Bastiaans

  DOI：10.1016/00404-0399(50)11539-

  日期：1995.8.14

  A flexible, convergent synthesis of Cyclotheonamide B (1b) was developed, starting from the constituent amino acids, using conventional benzyl-, t-butyl- and allyl-based protecting groups. By modification of the key intermediates, this approach allows the preparation of cyclotheonamide analogues.