L-alpha-甲基多巴甲基酯盐酸盐 | 115054-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: L-alpha-甲基多巴甲基酯盐酸盐
• 中文别名: L-α-甲基DOPA盐酸甲酯
• 英文名称: α-methyl-β-3,4-dihydroxyphenyl-(L)-alanine methyl ester hydrochloride
• 英文别名: 2-methyl-L-dopa methyl ester hydrochloride；H-L-Mdp-OMe*HCl；α-methyl-L-DOPA methyl ester hydrochloride；L-alpha-Methyl DOPA Methyl Ester Hydrochloride；methyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoate;hydrochloride
• CAS: 115054-62-1
• 化学式: C₁₁H₁₅NO₄*ClH
• 分子量: 261.705
• InChiKey: OGIAQNHFLNCESH-MERQFXBCSA-N

物化性质

• 熔点：
  196-198°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.95
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  L-alpha-甲基多巴甲基酯盐酸盐 在 TEA 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 136.25h， 生成 N^α-tert-butyloxycarbonyl-α-methyl-β-3,4-(benzo-24-crown-8)-phenyl-(L)-alanine methyl ester
  参考文献：
  名称：

  New crown-carrier Cα,α-disubstituted glycines derived from α-methyl-(l)-DOPA

  摘要：

  The side-chain catechol function of alpha-methyl-(L)-DOPA was utilized for the synthesis of a new series of crown-carrier C-alpha,C-alpha-disubstituted glycines. During N-protection of alpha-methyl-(L)-DOPA methyl ester (H-Mdp-OMe) with Boc anhydride, the formation of N,O-di-Boc derivatives was observed. Selective aminolysis of the catechol tert-butyl carbonate group was achieved using pyrrolidine as nucleophile. Treatment of the resulting Boc-Mdp-OMe by Cs2CO3 in MeOH, followed by bis-O-alkylation with cyclization using various polyethyleneglycol ditosylates or catechol-derived bis-polyethyleneglycol ditosylates in DMF at 60degreesC, led to the derivatives Boc-[15-C-5]-Mdp-OMe, Boc-[18-C-6]-Mdp-OMe, Boc-[benzo-18-C-6]-Mdp-OMe, Boc-[benzo-24-C-8]-Mdp-OMe and then after saponification, to the corresponding N-alpha-protected amino acids. The tripeptides Fmoc-Ala-[18-C-6]-Mdp-Ala-OMe and Boc-Aib-[18-C-6]-Mdp-Ala-OMe were prepared in solution by using Ala and Aib UNCAs for coupling at the N terminus of the [18-C-6]-Mdp residue and the EDC/HOAt method for coupling Ala at its C terminus. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)00566-5
• 作为产物：
  描述：

  methyl (S,E)-3-(benzo[d][1,3]dioxol-5-yl)-2-((4-chlorobenzylidene)amino)-2-methyl propanoate 在 盐酸 、 溶剂黄146 、 苯酚 作用下， 以 水 为溶剂， 反应 15.0h， 以91%的产率得到L-alpha-甲基多巴甲基酯盐酸盐
  参考文献：
  名称：

  协同路易斯酸/钯催化偶氮甲碱叶立德的催化不对称苄基化

  摘要：

  协同手性路易斯酸/非手性钯催化剂体系成功应用于各种亚胺酯的对映选择性苄基化反应，得到一系列α-苄基取代的α-氨基酸衍生物，收率令人满意，对映选择性优异。值得注意的是，该策略对双环和单环苄基亲电试剂具有良好的耐受性。此外，通过方便制备对映体富集的抗高血压药物 α-甲基-l-多巴，证明了该合成方案的实用性。

  DOI：

  10.1021/acs.orglett.2c00865

文献信息

• Sulphydryl compounds in melanogenesis
  作者：Marco d'Ischia、Alessandra Napolitano、Giuseppe Prota

  DOI：10.1016/s0040-4020(01)87714-0

  日期：1987.1

  glutathione to give a colourless adduct identified as 4-S-glutathionyl-5,6-dihydroxyindole (3). In the case of cysteine, the reaction leads to a non aminoacidic condensation product (λ max 422 nm) which was too unstable to be characterized. The analogous adduct derived by reaction of dopachrome methyl ester (9a) with cysteine ethyl ester (10a) could be isolated and formulated as 11a, containing the new

  在仿生条件下，多巴色素（1）是黑色素生物合成的关键中间体，已显示与谷胱甘肽反应生成无色加合物，被鉴定为4-S-谷胱甘肽-5,6-二羟基吲哚（3）。在半胱氨酸的情况下，该反应导致非氨基酸缩合产物（λmax 422nm），其太不稳定以至于无法表征。可以分离出由多巴色素甲酯（9a）与半胱氨酸乙酯（10a）反应得到的类似加合物，并将其配制成11a，其中包含新的1,2-二氢-3H，8H-吡咯[2,3-h] [ 1,4]苯并噻嗪环系统。同样地，2-甲基不饱和铬甲酯（9b）与10a和青霉胺甲酯（10b）反应，分别得到相应的加合物11b或11c。
• Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20030220521A1

  公开（公告）日：2003-11-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了一种肾选择性的前药，其在肾脏中优先转化为能够抑制参与肾交感神经活动的儿茶酚型神经递质合成的化合物。本文所描述的前药来源于能够抑制儿茶酚合成中的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，多巴脱羧酶抑制剂或多巴胺-&bgr;-羟化酶抑制剂。这些抑制剂化合物通过可被肾脏中大量存在的酶选择性识别的可裂解键与化学基团（如谷氨酸衍生物）连接。释放的抑制剂化合物然后可在肾脏中用于抑制儿茶酚合成中的一个或多个酶。抑制肾脏儿茶酚合成可抑制与钠潴留相关的疾病（如高血压）相关的增强肾脏神经活动。特别感兴趣的共轭物是多巴胺-&bgr;-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-&ggr;-谷氨酰富萨酸肼（如下图所示）是首选。1
• Synthesis, Ion Complexation Study, and 3D-Structural Analysis of Peptides Based on Crown-Carrier,Cα-Methyl-L-DOPA Amino Acids
  作者：Karen Wright、Rachid Anddad、Jean-François Lohier、Vincent Steinmetz、Michel Wakselman、Jean-Paul Mazaleyrat、Fernando Formaggio、Cristina Peggion、Marta De Zotti、Timothy A. Keiderling、Rong Huang、Claudio Toniolo

  DOI：10.1002/ejoc.200700917

  日期：2008.3

  terminally protected model peptides to the hexamer level, based on four novel, crown-ether containing Cα-methyl-L-DOPA (L-Mdp) amino acid residues, namely L-Mdp[15-C-5], L-Mdp[18-C-6], L-Mdp[benzo-24-C-8] and L-Mdp[(S)-Binol-20-C-6], combined with either L-Ala or L-Ala/Aib or Gly/Aib, were synthesized by solution methods. An ESI-MS analysis of their alkali metal cation complexation ability was carried out

  选定系列的六聚体水平的末端保护模型肽，基于四个新的、含 Cα-甲基-L-多巴 (L-Mdp) 氨基酸残基的冠醚，即 L-Mdp[15-C-5]、L -Mdp[18-C-6]、L-Mdp[benzo-24-C-8] 和 L-Mdp[(S)-Binol-20-C-6]，与 L-Ala 或 L-Ala 结合/Aib 或 Gly/Aib，通过溶液法合成。对其碱金属阳离子络合能力进行了 ESI-MS 分析。它们的 FTIR 吸收、1H NMR、ECD 和 VCD 光谱特性表明所有这些冠状氨基酸都是（左旋）β-转角和 310-螺旋结构的强诱导剂。（© Wiley-VCH Verlag GmbH & Co. KGaA , 69451 德国魏因海姆, 2008)
• New crown-carrier Cα,α-disubstituted glycines derived from α-methyl-(l)-DOPA
  作者：Karen Wright、Francesca Melandri、Caroline Cannizzo、Michel Wakselman、Jean-Paul Mazaleyrat

  DOI：10.1016/s0040-4020(02)00566-5

  日期：2002.7

  The side-chain catechol function of alpha-methyl-(L)-DOPA was utilized for the synthesis of a new series of crown-carrier C-alpha,C-alpha-disubstituted glycines. During N-protection of alpha-methyl-(L)-DOPA methyl ester (H-Mdp-OMe) with Boc anhydride, the formation of N,O-di-Boc derivatives was observed. Selective aminolysis of the catechol tert-butyl carbonate group was achieved using pyrrolidine as nucleophile. Treatment of the resulting Boc-Mdp-OMe by Cs2CO3 in MeOH, followed by bis-O-alkylation with cyclization using various polyethyleneglycol ditosylates or catechol-derived bis-polyethyleneglycol ditosylates in DMF at 60degreesC, led to the derivatives Boc-[15-C-5]-Mdp-OMe, Boc-[18-C-6]-Mdp-OMe, Boc-[benzo-18-C-6]-Mdp-OMe, Boc-[benzo-24-C-8]-Mdp-OMe and then after saponification, to the corresponding N-alpha-protected amino acids. The tripeptides Fmoc-Ala-[18-C-6]-Mdp-Ala-OMe and Boc-Aib-[18-C-6]-Mdp-Ala-OMe were prepared in solution by using Ala and Aib UNCAs for coupling at the N terminus of the [18-C-6]-Mdp residue and the EDC/HOAt method for coupling Ala at its C terminus. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Catalytic Asymmetric Benzylation of Azomethine Ylides Enabled by Synergistic Lewis Acid/Palladium Catalysis
  作者：Xin Chang、Jing-Di Ran、Xue-Tao Liu、Chun-Jiang Wang

  DOI：10.1021/acs.orglett.2c00865

  日期：2022.4.8

  synergistic chiral Lewis acid/achiral Pd catalyst system was successfully applied in the enantioselective benzylation of various imine esters, giving a range of α-benzyl-substituted α-amino acid derivatives in satisfactory yield with excellent enantioselectivity. It is worth noting that this strategy exhibits good tolerance for bicyclic and monocyclic benzylic electrophiles. Furthermore, the utility of this

  协同手性路易斯酸/非手性钯催化剂体系成功应用于各种亚胺酯的对映选择性苄基化反应，得到一系列α-苄基取代的α-氨基酸衍生物，收率令人满意，对映选择性优异。值得注意的是，该策略对双环和单环苄基亲电试剂具有良好的耐受性。此外，通过方便制备对映体富集的抗高血压药物 α-甲基-l-多巴，证明了该合成方案的实用性。