N-Methyl-L-phenylalanine phenylmethyl ester | 47091-20-3

• 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-Methyl-L-phenylalanine phenylmethyl ester
• 英文别名: N-methylphenylalanine benzyl ester；N-methyl phenylalanine；N-Methyl-L-phenylalanin-benzylester；benzyl (2S)-2-(methylamino)-3-phenylpropanoate
• CAS: 47091-20-3
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: YRLRVIREPVEFJA-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Methyl-L-phenylalanine phenylmethyl ester 在 palladium on activated charcoal N-甲基吗啉 、 二苯基磷酸 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 碳酸氢钠 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 leualacin
  参考文献：
  名称：

  Total Synthesis of the Cyclic Depsipeptide Leualacin

  摘要：

  The fungal metabolite leualacin (1), a potent calcium channel antagonist, was synthesized in 15 steps from commercially available amino acids in 25% overall yield using standard solution methods. The synthesis is general and thus would accommodate the incorporation of amino acid replacements as well as the inclusion of peptide mimics and isosteres.

  DOI：

  10.1021/jo00124a019
• 作为产物：
  描述：

  Boc-N-甲基-L-苯丙氨酸 在 4-二甲氨基吡啶 、 4-(dimethylamino)pyridine hydrochloride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-Methyl-L-phenylalanine phenylmethyl ester
  参考文献：
  名称：

  Total Synthesis of the Cyclic Depsipeptide Leualacin

  摘要：

  The fungal metabolite leualacin (1), a potent calcium channel antagonist, was synthesized in 15 steps from commercially available amino acids in 25% overall yield using standard solution methods. The synthesis is general and thus would accommodate the incorporation of amino acid replacements as well as the inclusion of peptide mimics and isosteres.

  DOI：

  10.1021/jo00124a019

文献信息

• Synthesis and Biological Activity of Peptides Related to Eledoisin. II. Hexapeptide Amides Containing<i>N</i>-Methylamino Acids
  作者：Hiroshi Sugano、Ko Higaki、Muneji Miyoshi

  DOI：10.1246/bcsj.46.231

  日期：1973.1

  Eledoisin-like hexapeptides were synthesized in order to obtain longer-lasting hypotensive analogs. A part of the amino acid of the standard pep tide, H–Lys–Phe–Ile–Gly–Leu–Met–NH2 (1), was replaced by N-methylamino acid. It was found, in these syntheses, that when the C-terminal amino acid of a carboxy component was an N-methylamino acid, a system of dicyclohexylcarbodiimide plus 1-hydroxybenzotriazole was a useful coupling agent. With regard to the hypotensive effect in rabbits, H–Lys–Phe–Melle–Gly–Leu–Met–NH2 (2) and H–Lys–Phe–Ile–Gly–Melle–Met–NH2 (6) show much less activity; H–Lys–MePhe–Ile–Gly–Leu–Met–NH2 (3) and H–Lys–MePhe–Ile–Gly–MeLeu–Met–NH2 (7) show a substantial activity, though weaker than the standard one. On the other hand, H–Lys–Phe–Ile–Gly–MeLeu–Met–NH2 (5) and H–Lys–Phe–Ile–Sar–Leu–Met–NH2(4) show a higher activity than 1. These results indicate that, in some cases, the replacement of an amide bond by an N-methylamide bond without any change in the side chain of amino acid would have an important influence on the activity. The duration of the action of N-methypeptildes synthesized was unexpectedly of the same order of magnitude as that of 1.

  为获得更持久降压效果的模拟物，合成了促咽激素样六肽。将标准肽H-Lys-Phe-Ile-Gly-Leu-Met-NH2（1）中的部分氨基酸替换为N-甲基氨基酸。在这些合成中，发现当羧基部分C末端氨基酸为N-甲基氨基酸时，二环己基碳二亚胺加1-羟基苯并三唑是一种有用的偶联剂。关于对兔子的降压效果，H-Lys-Phe-Melle-Gly-Leu-Met-NH2（2）和H-Lys-Phe-Ile-Gly-Melle-Met-NH2（6）的活性大大降低；H-Lys-MePhe-Ile-Gly-Leu-Met-NH2（3）和H-Lys-MePhe-Ile-Gly-MeLeu-Met-NH2（7）显示出相当的活性，尽管弱于标准肽。另一方面，H-Lys-Phe-Ile-Gly-MeLeu-Met-NH2（5）和H-Lys-Phe-Ile-Sar-Leu-Met-NH2（4）的活性高于1。这些结果表明，在某些情况下，将酰胺键替换为N-甲基酰胺键而不改变氨基酸侧链会对活性产生重要影响。合成的N-甲基肽的作用持续时间与1相当。
• <i>C</i>-Alkylation of Peptides through Polylithiated and LiCl-Solvated Derivatives Containing Sarcosine Li-Enolate Units
  作者：Dieter Seebach、Hans Bossler、Hansjörg Gründler、Shin-Ichiro Shoda、Roland Wenger

  DOI：10.1002/hlca.19910740121

  日期：1991.1.30

  respectively), and thus C-alkylated on sarcosine (Sar) moieties with MeI and allyl or PhCH2Br. The polylithiated species are solubilized in THF, and their reactivity modified by excess base (lithium diisopropylamide (LDA)), by added LiCl, and/or the cosolvent N,N′-dimethylpropyleneurea (DMPU). Optimization of the reaction conditions for methylation in the cases of 7b (Table 3) and 12b (Scheme 8) gave products

  三肽和六肽衍生物Boc-Gly-Sar-MeLeu-OH（5b），Boc-Ala-Sar-Sar-OH（6b），Boc-Ala-Sar-MeLeu-OH（7b）和Boc-Abu-Sar -OH -MeLeu-Val-MeLeu-Ala-OH（12b）可以被多去质子化（分别为三硫代和五硫代衍生物K和P），并因此在肌氨酸（Sar）部分上用MeI和烯丙基或PhCH 2 Br进行C-烷基化。将多晶化的物质溶解在THF中，并通过添加过量的碱（二异丙基氨基锂（LDA）），添加的LiCl和/或助溶剂N，N来改变其反应活性。′-二甲基丙烯脲（DMPU）。优化7b（表3）和12b（方案8）情况下的甲基化反应条件，得到的产物中，离析物的Sar残基已转化为Me-D-Ala单元，产率为80（9c / 8c）和67％（14c / 13c），非对映选择性约为ca。4：1。三肽5b和6b仅包含一个立体生成中心，观察到选
• Influence of stereochemistry on the activity of rapadocin, an isoform-specific inhibitor of the nucleoside transporter ENT1
  作者：Yuefan Wang、Hanjing Peng、Zufeng Guo、Brett R. Ullman、Kana Yamamoto、Sam Y. Hong、Jun O. Liu

  DOI：10.1039/d1sc02295d

  日期：——

  two different synthetic strategies and the assignment of their structures. The inhibitory activity of each of the four synthetic isomers on both hENT1 and hENT2 was determined. It was found that the stereochemistry of phenylglycine played a more dominant role than the configuration of the olefin in the activity of rapadocin. These findings will guide the future design and development of rapadocin analogs

  Rapadocin 是一种新型的受雷帕霉素启发的聚酮化合物-四肽杂化大环化合物，对人类平衡核苷转运蛋白 1 (hENT1) 具有高效和同种型特异性抑制活性。Rapadocin 在苯基甘氨酸中包含一个可差向异构的手性中心和一个烯烃基团，因此可以作为四种立体异构体的混合物存在。在此，我们报告了使用两种不同合成策略的 rapadocin 四种立体异构体的首次全合成及其结构分配。测定了四种合成异构体中的每一种对 hENT1 和 hENT2 的抑制活性。发现苯基甘氨酸的立体化学在rapadocin的活性中比烯烃的构型起主导作用。
• Selective C–N bond oxidation: demethylation of N-methyl group in N-arylmethyl-N-methyl-α-amino esters utilizing N-iodosuccinimide (NIS)
  作者：Takahiro Katoh、Tsunefumi Watanabe、Mitsuyoshi Nishitani、Minoru Ozeki、Tetsuya Kajimoto、Manabu Node

  DOI：10.1016/j.tetlet.2007.11.162

  日期：2008.1

  Demethylation of N-methyl group in N-methyl-N-arylmethyl-α-amino esters was accomplished by the oxidation of the amino group using the N-iodosuccinimide (NIS)/acetonitrile system followed by treatment with O-methylhydroxylamine hydrochloride. This combination of reagents could provide a complementary method to catalytic hydrogenolysis, which certainly cleaves N-arylmethyl groups, in organic synthesis

  脱甲基化Ñ在甲基组Ñ甲基Ñ -arylmethyl-α氨基酯是通过使用氨基的氧化完成Ñ碘代丁二酰亚胺（NIS）/乙腈系统随后用治疗ö -methylhydroxylamine盐酸盐。试剂的这种结合可以为有机合成中的催化氢解提供补充方法，该催化氢解肯定会裂解N-芳基甲基。
• Pyroglutamic acid derivatives and related compounds which inhibit leukocyte adhesion mediated by VLA-4
  申请人：ELAN PHARMACEUTICALS, INC.

  公开号：EP1612215A1

  公开（公告）日：2006-01-04

  Disclosed are pyroglutamic acid derivatives and related compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g. human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

  本文披露了与VLA-4结合的吡咯烷酸衍生物和相关化合物。其中某些化合物还抑制白细胞粘附，特别是通过VLA-4介导的白细胞粘附。这些化合物在治疗哺乳动物患者（例如人类）的炎症性疾病中非常有用，如哮喘、阿尔茨海默病、动脉粥样硬化、艾滋病痴呆、糖尿病、炎症性肠病、类风湿性关节炎、组织移植、肿瘤转移和心肌缺血。这些化合物还可用于治疗多发性硬化等炎症性脑部疾病。