methyl (-)-(3R)-3-amino-3-(4-methoxyphenyl)propanoate | 131791-82-7

• 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: methyl (-)-(3R)-3-amino-3-(4-methoxyphenyl)propanoate
• 英文别名: (R)-β-tyrosine-O-methyl ether methyl ester；methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate；methyl L-2-amino-3-(4-methoxyphenyl)propanoate；(R)-Methyl 3-amino-3-(4-methoxyphenyl)-propanoate
• CAS: 131791-82-7
• 化学式: C₁₁H₁₅NO₃
• 分子量: 209.245
• InChiKey: JLQUEGAVLHIIBF-SNVBAGLBSA-N

物化性质

• 沸点：
  324.5±37.0 °C(Predicted)
• 密度：
  1.117±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (-)-(3R)-3-amino-3-(4-methoxyphenyl)propanoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 cyclo[Leu-Leu-Val-Leu-Tyr(Me)]
  参考文献：
  名称：

  Effect of the 4′-substituted phenylalanine moiety of sansalvamide A peptide on antitumor activity

  摘要：

  合成了8种具有4'²-氟、4'²-氯、4'²-溴、4'²-碘和4'²-甲氧基苯丙氨酸分子的山沙酰胺A肽类似物。研究人员使用 HCT-116、MDA-MB-231、HT-29、HCT-15、K562、HeLa 和 A549 细胞系评估了山沙酰胺 A 肽的这些对位取代对其细胞毒性的影响。结果发现，4²-甲氧基苯丙氨酸类似物丹沙酰胺 A肽是一种很有前景的抗肿瘤药物。

  DOI：

  10.1039/c3md00294b
• 作为产物：
  描述：

  3-氨基-3-(4-甲氧基苯基)丙酸 在 盐酸 作用下， 反应 1.0h， 生成 methyl (-)-(3R)-3-amino-3-(4-methoxyphenyl)propanoate
  参考文献：
  名称：

  Asymmetric Syntheses of the Macrocyclic Spermine Alkaloids (−)-(S)-Protoverbine, (−)-(S)-Buchnerine, and Their Naturally Occurring Congenial Alkaloids

  摘要：

  Asymmetric syntheses of the following 17-membered macrocyclic spermine alkaloids are presented: (-)-(S)-protoverbine (= (8S)-8-phenyl-1,5,9,13-tetraazacycloheptadecane-6-one; 1), (+)-(S)-protomethine (=(2S)-2-phenyl-1,5,9,14-tetraazabicyclo[12.3.1]octadecan-4-one; 2), (-)-(S)-buchnerine (=(8S)-8-(4-methoxyphenyl)-1,5,9,13-tetraazacycloheptadecane-6-one; 8), (+)-(S)-VeTbamethine (=(-')-(2S)-9-[(E)-phenylprop- 2-enoyl]-2-phenyl-1,5,9,14-tetraazabicyclo[12.3.1]octadecan-4-one; 4), (-)-(S)-verbacine [(E)-phenylprop-2-enoyl]-8-phenyl-1,5,9,13-tetraazacycloheptadecan-6-one; 3), (-)-(S)-verbasikrine (8S)-1-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-8-phenyl-1,5,9,13-tetraazacycloheptadecan-6-one; 26), (S)-isoverbasikrine (=(-)-(8S)-1-[(Z)-3-(4-methoxyphenyl)prop-2-enoyl]-8-phenyl-1,5,9,13-tetraazacycloheptadecan-6-one; 25), (+)-(S)-verbamekrine (= (+)-(2S)-9-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-2-phenyl- 1,5,9.14-tetraazabicyclo[12.3.1]octadecan-4- one; 23), and(+)-(S)-isoverbamekrine (=(+)-(2S)-9-[(Z)-3-(4-methoxyphenyl)prop-2-enoyl]-2-phenyl-1,5,9,14-tetraazabicyclo[12.3.1]octadecan-4-one; 24). Effective methods for H-1-NMR determination of the enantiomeric purity in which (S)-2-hydroxy-2-phenylacetic acid and (S)-2-acetoxy-2-phenylacetic acid are used as shift reagents for 1, 8, and related macrocyclic alkaloids are described.

  DOI：

  10.1002/1522-2675(200204)85:4<979::aid-hlca979>3.0.co;2-f

文献信息

• Triclorosilane-mediated stereoselective synthesis of β-amino esters and their conversion to highly enantiomerically enriched β-lactams
  作者：Stefania Guizzetti、Maurizio Benaglia、Martina Bonsignore、Laura Raimondi

  DOI：10.1039/c0ob00570c

  日期：——

  A highly stereoselective trichlorosilane-mediated reduction of N-benzyl enamines was developed; the combination of a low cost, easy to make metal-free catalyst and an inexpensive chiral auxiliary allowed to perform the reaction on substrates with different structural features often with total control of the stereoselectivity. By easy deprotection through hydrogenolysis followed by conversion of β-aminoester

  已经开发出高度立体选择性的三氯硅烷介导的N-苄基烯胺的还原；低成本，易于制造的不含金属的催化剂与廉价的手性助剂的结合，通常可以完全控制立体选择性，从而在具有不同结构特征的底物上进行反应。通过容易的氢解脱保护，然后将β-氨基酯转化为2-氮杂环丁酮，对映体纯的β-内酰胺（> 98％ee）成功地完成了合成。
• Catalytic Asymmetric Mannich Reactions of Sulfonylacetates
  作者：Carlo Cassani、Luca Bernardi、Francesco Fini、Alfredo Ricci

  DOI：10.1002/anie.200900701

  日期：2009.7.20

  synthetic equivalents of a variety of α‐carboxylate anions. Phase‐transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from α‐amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of β‐amino acid derivatives.

  砜与砜：芳基磺酰乙酸盐可以看成是各种α-羧酸根阴离子的合成等价物。相转移催化（PTC）使它们能够轻度去质子化，并催化不对称添加到α-酰胺基砜现场生成的高反应性亚胺上（见方案； Pg =保护基）。通过将其直接转化为一系列β-氨基酸衍生物，证明了该产品的合成效用。
• Stereoselective Chemoenzymatic Preparation of β-Amino Esters: Molecular Modelling Considerations in Lipase-Mediated Processes and Application to the Synthesis of (<i>S</i>)-Dapoxetine
  作者：María Rodríguez-Mata、Eduardo García-Urdiales、Vicente Gotor-Fernández、Vicente Gotor

  DOI：10.1002/adsc.200900676

  日期：2010.2.15

  the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these

  已经通过立体选择性化学酶法制备了多种旋光的3-氨基-3-芳基丙酸衍生物。关键步骤是相应的β-氨基酯的动力学拆分。尽管氨基用甲氧基乙酸乙酯的酶促酰化显示了合成上有用的对映选择性，但是已经鉴定出由洋葱假单胞菌的脂肪酶催化的酯基的水解是关于活性和对映选择性的最佳方法。在分子水平上，已通过使用基于片段的方法解释了这些脂​​肪酶在这些反应中的对映体优先性，其中最有利的苯环结合位点和最稳定的3-氨基丙酸酯核心构象与（小号）-主要产品的配置。为了理解苯环中存在的不同取代模式的影响，已经比较了酶促反应的转化率和对映选择性值。该化学酶途径已成功地用于制备（S）-达泊西汀合成中的有价值的中间体，该中间体已经以优异的光学纯度化学合成。
• Highly Efficient Synthesis of β-Amino Acid Derivatives via Asymmetric Hydrogenation of Unprotected Enamines
  作者：Yi Hsiao、Nelo R. Rivera、Thorsten Rosner、Shane W. Krska、Eugenia Njolito、Fang Wang、Yongkui Sun、Joseph D. Armstrong、Edward J. J. Grabowski、Richard D. Tillyer、Felix Spindler、Christophe Malan

  DOI：10.1021/ja047901i

  日期：2004.8.1

  A direct asymmetric hydrogenation of unprotected enamino esters and amides is described. Catalyzed by Rh complexes with Josiphos-type chiral ligands, this method gives beta-amino esters and amides in high yield and high ee (93-97% ee). No acyl protection/deprotection is required.

  描述了未保护的烯氨基酯和酰胺的直接不对称氢化。该方法由具有 Josiphos 型手性配体的 Rh 络合物催化，以高产率和高 ee (93-97% ee) 得到 β-氨基酯和酰胺。不需要酰基保护/脱保护。
• Self-reproduction of chirality. Asymmetric synthesis of .beta.-aryl-.beta.-amino acids from enantiomerically pure dihydropyrimidinones
  作者：Joseph P. Konopelski、Kent S. Chu、George R. Negrete

  DOI：10.1021/jo00004a005

  日期：1991.2

  Enantiomerically pure dihydropyrimidinone 1 reacts with aryl iodides in the presence of catalytic amounts of Pd(OAc)2 and added phosphine to afford dihydropyrimidinone 4, in which a formal conjugate addition of the aryl group to the alpha,beta-unsaturated system has occurred. Application of this methodology to the synthesis of a protected version of the tripeptide portion of the natural product jasplakinolide is presented.