N^α-tert-butyloxycarbonyl-O-methyl-(S)-tyrosine methylamide | 122900-19-0

• 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-O-methyl-(S)-tyrosine methylamide
• 英文别名: N-(tert-butyloxycarbonyl)-O-(methyl)-L-tyrosine methylamide；tert-butyl N-[(2S)-3-(4-methoxyphenyl)-1-(methylamino)-1-oxopropan-2-yl]carbamate
• CAS: 122900-19-0
• 化学式: C₁₆H₂₄N₂O₄
• 分子量: 308.378
• InChiKey: XLHOSUAOQBCFIS-ZDUSSCGKSA-N

物化性质

• 熔点：
  76-77 °C
• 沸点：
  516.4±50.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.66
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N^α-tert-butyloxycarbonyl-O-methyl-(S)-tyrosine methylamide 在 盐酸 、 sodium tetrahydroborate 、 3 A molecular sieve 、 三甲基铝 作用下， 以 1,4-二氧六环 、 甲醇 、 溶剂黄146 为溶剂， 反应 37.0h， 生成 N-<(1R-(1α,2α,3α))-2-(hydroxymethyl)-3-(2-propyl)-cyclopropanoyl>-N'-(p-methoxybenzyl)-O-methyl-L-tyrosine-N-methylamide
  参考文献：
  名称：

  Cyclopropanes as conformationally restricted peptide isosteres. Design and synthesis of novel collagenase inhibitors

  摘要：

  The 1,2,3-trisubstituted cyclopropane derivatives 9 and 10 were prepared as conformationally constrained analogues of the known collagenase inhibitor 8. The syntheses of 9 and 10 featured the highly enantioselective Rh2[S-MEPY]4 catalyzed cyclization of the, allylic diazo ester 11 to give the lactone 13. Opening of the lactone ring of 13 with N,O-di-(p-methoxybenzyl)hydroxylamine under Weinreb conditions followed by refunctionalization, coupling of the intermediate acid 16 with 17 and deprotection led to the dipeptide analogue 9. Alternatively, the lactone ring of 13 could be opened with the protected tyrosine 21 by a novel variant of the Weinreb protocol to give directly the dipeptide analogue 22 which was then converted into 10.

  DOI：

  10.1016/s0040-4020(01)90212-1
• 作为产物：
  描述：

  Boc-L-酪氨酸 在 N-甲基吗啉 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 生成 N^α-tert-butyloxycarbonyl-O-methyl-(S)-tyrosine methylamide
  参考文献：
  名称：

  Cyclopropanes as conformationally restricted peptide isosteres. Design and synthesis of novel collagenase inhibitors

  摘要：

  The 1,2,3-trisubstituted cyclopropane derivatives 9 and 10 were prepared as conformationally constrained analogues of the known collagenase inhibitor 8. The syntheses of 9 and 10 featured the highly enantioselective Rh2[S-MEPY]4 catalyzed cyclization of the, allylic diazo ester 11 to give the lactone 13. Opening of the lactone ring of 13 with N,O-di-(p-methoxybenzyl)hydroxylamine under Weinreb conditions followed by refunctionalization, coupling of the intermediate acid 16 with 17 and deprotection led to the dipeptide analogue 9. Alternatively, the lactone ring of 13 could be opened with the protected tyrosine 21 by a novel variant of the Weinreb protocol to give directly the dipeptide analogue 22 which was then converted into 10.

  DOI：

  10.1016/s0040-4020(01)90212-1

文献信息

• Secondary structure binding motifs of the jet cooled tetrapeptide model Ac–Leu–Val–Tyr(Me)–NHMe
  作者：H. Fricke、G. Schäfer、T. Schrader、M. Gerhards

  DOI：10.1039/b706519a

  日期：——

  In this paper the structure of the isolated tetrapeptide model Ac–Leu–Val–Tyr(Me)–NHMe (Leu = leucine, Val = valine, Tyr = tyrosine) is investigated by mass- and isomer-selective IR/UV double resonance spectroscopy. Two isomers of this peptide are observed and in combination with force field, ab initio, and DFT calculations these structures are assigned to folded arrangements presenting two different secondary structure binding motifs: (a) a combined γ-turn/β-turn structure and (b) a triple γ-turn structure, which is described for the first time for an isolated model system in the gas phase.

  本文通过质量和同分异构体选择性红外/紫外双共振光谱法研究了分离的四肽模型 AcâLeuâValâTyr(Me)âNHMe （Leu = 亮氨酸，Val = 缬氨酸，Tyr = 酪氨酸）的结构。结合力场、ab initio 和 DFT 计算，观察到了这种肽的两种异构体，并将这些结构归结为折叠排列，呈现出两种不同的二级结构结合图案：(a) δ-匝/δ-²-匝组合结构和 (b) 三重δ-匝结构。
• Structure of the tripeptide model Ac–Val–Tyr(Me)–NHMe and its cluster with water investigated by IR/UV double resonance spectroscopy
  作者：H. Fricke、A. Gerlach、C. Unterberg、P. Rzepecki、T. Schrader、M. Gerhards

  DOI：10.1039/b407174c

  日期：——

  In this paper the structures of the isolated tripeptide model Ac–Val–Tyr(Me)–NHMe (Val = valine, Tyr = tyrosine) and its cluster with water are investigated by mass-, isomer- and state-selective IR/UV double resonance spectroscopy. From the IR spectra both in the region of the NH and CO stretching vibrations and in combination with force field and ab initio calculations it can unambiguously be derived

  本文通过质量选择性、异构体选择性和状态选择性红外/紫外双键研究了分离的三肽模型 Ac–Val–Tyr(Me)–NHMe（Val = 缬氨酸，Tyr = 酪氨酸）及其与水的簇的结构。共振光谱。从 NH 和 CO 伸缩振动区域中的 IR 光谱以及结合力场和从头算计算，可以明确得出肽包含拉伸的 β-折叠相关结构。因此，该肽可作为 β-折叠模型系统的理想候选者。通过向肽添加一个水分子，β-折叠相关结构似乎被保留，水分子连接到 NHMe 基团。
• Phosphoramidate peptide inhibitors of human skin fibroblast collagenase
  作者：Zbigniew P. Kortylewicz、Richard E. Galardy

  DOI：10.1021/jm00163a044

  日期：1990.1

  An extensive series of N-(monoethylphosphoryl)peptides was synthesized and their inhibition of purified human skin fibroblast collagenase examined. At the cleavage site S1 all reported compounds have the (EtO)(OK)P(O) group and the peptide side chain extended toward the C-terminal end (up to P5') of the substrate sequence. These phosphoramidates with a tetrahedrally hybridized phosphorus atom are thought to be transition state analogue inhibitors. They exhibited fair inhibitory potency against this vertebrate collagenase having Ki values in the micromolar range. The most potent of these, (EtO)(OK)P(O)-Ile-TrpNHCH3 (68), inhibits with a Ki value of 1.5 microM and is nearly 100 times stronger than (EtO)(OK)P(O)-Ile-Ala-GlyOK (51) (Ki of 140 microM), which has the sequence matching that of the alpha 1 (I) chain of collagen in P1', P2', P3' after the cleavage site. Several compounds were prepared in an attempt to identify the nature of the S2', S3', and S4' binding sites. Alanine at the P2' position was replaced by leucine, phenylalanine, tryptophan, or tyrosine derivatives, resulting in Ki values in a significantly lower range, 1.0-40 microM, compared to 51. No upper size limitation or specificity has been found at this position, yet similar replacements at the P3' position, which is occupied naturally by a glycine residue, gave weaker inhibitors: (EtO)(OK)P(O)-Ile-Tyr(OBzl)-PheOK (57) had a Ki of 120 microM. Hexapeptide derivatives had weaker activities in the 270 microM-2 mM range. All inhibitors were evaluated by using the synthetic thio peptolide spectrophotometric assay.
• Pozdnev, Russian Journal of Bioorganic Chemistry, 1997, vol. 23, # 4, p. 241 - 244
  作者：Pozdnev

  DOI：——

  日期：——
• KORTYLEWICZ, ZBIGNIEW P.;GALARDY, RICHARD E., J. MED. CHEM., 33,(1990) N, C. 263-273
  作者：KORTYLEWICZ, ZBIGNIEW P.、GALARDY, RICHARD E.

  DOI：——

  日期：——