allyl 2(S)-(acetylamino)-3-[[4(S)-[(2(R)-{[2(R,S)-hydroxy-3(S)-({[1-(allyloxycarbonyl)pyrrolidin-2(S)-yl]carbonyl}amino)-6-({[(tert-butyloxycarbonyl)imino][(tert-butyloxycarbonyl)amino]methyl}amino)hexanoyl]amino}-3-phenylpropanoyl)amino]-5-[4-(tert-... | 190203-27-1

• 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: allyl 2(S)-(acetylamino)-3-[[4(S)-[(2(R)-{[2(R,S)-hydroxy-3(S)-({[1-(allyloxycarbonyl)pyrrolidin-2(S)-yl]carbonyl}amino)-6-({[(tert-butyloxycarbonyl)imino][(tert-butyloxycarbonyl)amino]methyl}amino)hexanoyl]amino}-3-phenylpropanoyl)amino]-5-[4-(tert-...
• 英文别名: prop-2-enyl (2S)-2-[[(3S)-1-[[(2R)-1-[[(E,2S)-5-[[(2S)-2-acetamido-3-oxo-3-prop-2-enoxypropyl]amino]-1-[4-[(2-methylpropan-2-yl)oxy]phenyl]-5-oxopent-3-en-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-6-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-hydroxy-1-oxohexan-3-yl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 190203-27-1
• 化学式: C₅₈H₈₃N₉O₁₅
• 分子量: 1146.35
• InChiKey: UAOLJGIVUHJZGP-WLHZUJEXSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  82
• 可旋转键数：
  35
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  320
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  allyl 2(S)-(acetylamino)-3-[[4(S)-[(2(R)-{[2(R,S)-hydroxy-3(S)-({[1-(allyloxycarbonyl)pyrrolidin-2(S)-yl]carbonyl}amino)-6-({[(tert-butyloxycarbonyl)imino][(tert-butyloxycarbonyl)amino]methyl}amino)hexanoyl]amino}-3-phenylpropanoyl)amino]-5-[4-(tert-... 在 吗啉 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 茴香硫醚 、 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 、 三氟乙酸 、 叔丁醇 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 49.5h， 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：

  methyl ((3S)-3-amino-6-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-hydroxyhexanoyl)-D-phenylalaninate 在 lithium hydroxide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.7h， 生成 allyl 2(S)-(acetylamino)-3-[[4(S)-[(2(R)-{[2(R,S)-hydroxy-3(S)-({[1-(allyloxycarbonyl)pyrrolidin-2(S)-yl]carbonyl}amino)-6-({[(tert-butyloxycarbonyl)imino][(tert-butyloxycarbonyl)amino]methyl}amino)hexanoyl]amino}-3-phenylpropanoyl)amino]-5-[4-(tert-...
  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