N^α-(tert-butyloxycarbonyl)-γ-methylleucine benzyl ester | 140897-41-2

• 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: N^α-(tert-butyloxycarbonyl)-γ-methylleucine benzyl ester
• 英文别名: L-Leucine, N-[(1,1-dimethylethoxy)carbonyl]-4-methyl-, phenylmethyl ester (9CI)；benzyl (2S)-4,4-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 140897-41-2
• 化学式: C₁₉H₂₉NO₄
• 分子量: 335.444
• InChiKey: FRAJHZJJSTUZMY-HNNXBMFYSA-N

物化性质

• 沸点：
  436.6±28.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N^α-(tert-butyloxycarbonyl)-γ-methylleucine benzyl ester 在 盐酸 、 甲烷 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 2.0h， 生成 isocyanato-γ-methylleucine benzyl ester
  参考文献：
  名称：

  An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788

  摘要：

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.

  DOI：

  10.1021/jo00130a028
• 作为产物：
  描述：

  溴甲苯 、 N-(tert-butoxycarbonyl)-L-tert-leucine 在 CsCO₃ 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以91%的产率得到N^α-(tert-butyloxycarbonyl)-γ-methylleucine benzyl ester
  参考文献：
  名称：

  An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788

  摘要：

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.

  DOI：

  10.1021/jo00130a028

文献信息

• Antiherpes peptide derivatives having a 1,4-dioxo-C, N-terminus
  申请人：Bio-Mega/Boehringer Ingelheim Research Inc.

  公开号：US05484771A1

  公开（公告）日：1996-01-16

  Described herein are peptide derivatives of the formula R.sup.1 NH--CO--Q--C(O)--NR.sup.2 --CH[CH.sub.2 C(O)--Y]--C(O)--NH--CH[CR.sup.3 (R.sup.4)--COOH]--C(W)--NH--CHR.sup.5 --Z wherein R.sup.1 is an optionally substituted alkyl or optionally substituted phenylalkyl, R.sup.2 is hydrogen or alkyl, R.sup.3 and R.sup.4 each independently is hydrogen or alkyl, or R.sup.3 and R.sup.4 are joined to form a cycloalkyl. R.sup.5 is alkyl, cycloalkyl or (cycloalkyl)alkyl, Q is a divalent radical, for example, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH-- or 1,2-cyclohexanediyl, which serves as a two carbon spacer. W is oxo or thioxo, Y is, for example, an alkoxy or a monosubstituted or disubsdtuted ammo, and Z is a terminal unit, for example, hydrogen, COOH or CH.sub.2 OH. The derivatives are useful for treating herpes infections.

  本文描述了公式R.sup.1 NH--CO--Q--C(O)--NR.sup.2 --CH[CH.sub.2 C(O)--Y]--C(O)--NH--CH[CR.sup.3 (R.sup.4)--COOH]--C(W)--NH--CHR.sup.5 --Z的肽衍生物。其中，R.sup.1是可选择取代的烷基或可选择取代的苯基烷基，R.sup.2是氢或烷基，R.sup.3和R.sup.4各自独立地是氢或烷基，或者R.sup.3和R.sup.4结合形成环烷基。R.sup.5是烷基、环烷基或(环烷基)烷基，Q是二价基团，例如，--CH.sub.2 CH.sub.2 --、--CH.dbd.CH--或1,2-环己基二基，用作两个碳的间隔。W是氧或硫氧，Y是例如烷氧基或单取代或双取代的氨基，Z是一个末端基元，例如氢、COOH或CH.sub.2 OH。这些衍生物对治疗疱疹感染有用。
• An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788
  作者：John X. He、Wayne L. Cody、Annette M. Doherty

  DOI：10.1021/jo00130a028

  日期：1995.12

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.