(2S,3S)-methylphenylalanine | 25488-25-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2S,3S)-methylphenylalanine
• 英文别名: (2S,3S)-β-methylphenylalanine；L-erythro-β-methyl-phenylalanine；erythro-(2S,3S)-(-)-3-methylphenylalanine；(2S,3S)-2-amino-3-phenyl-butyric acid；(2S,3S)-2-azaniumyl-3-phenylbutanoate
• CAS: 25488-25-9
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: IRZQDMYEJPNDEN-CBAPKCEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S)-methylphenylalanine 在 硫酸 、 硝酸 作用下， 反应 0.5h， 以70%的产率得到(S,S)-erythro-β-methyl-p-nitro-L-phenylalanine
  参考文献：
  名称：

  Topographically designed analogs of [cyclic] [D-Pen2,D-Pen5]enkephalin

  摘要：

  The conformationally restricted, cyclic disulfide-containing delta-opioid receptor selective enkephalin analogue [D-Pen2, D-Pen5]enkephalin (1, DPDPE) was systematically modified topographically by addition of a methyl group at either the pro-S or pro-R position of the beta-carbon of an L-Phe4 or D-Phe4 residue to give [(2S,3S)-beta-MePhe4]DPDPE (2), [(2R,3R)-beta-MePhe4]DPDPE (3), [(2S,3R)-beta-MePhe4]DPDPE (4), and [(2R,3S)-beta-MePhe4]DPDPE (5). The four corresponding isomers were prepared in which the beta-methylphenylalanine residue was p-nitro substituted, that is with a beta-methyl-p-nitrophenylalanine (beta-Me-p-NO2Phe) residue, to give [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (6), [(2R,3R)-beta-Me-p-NO2Phe4]DPDPE (7),[(2S,3R)-beta-Me-p-NO2Phe4]DPDPE (8), and [(2R,3S)-beta-Me-p-NO2Phe4]DPDPE (9), respectively. The potency and selectivity (delta vs mu-opioid receptor) were evaluated by radioreceptor binding assays in the rat brain using [H-3]CTOP (mu-ligand) and [H-3]DPDPE (delta-ligand) and by bioassay with mouse vas deferens (MVD, delta-receptor assay) and guinea pig ileum (GPI, mu-receptor assay). The eight analogues of DPDPE showed highly variable binding and bioassay activities particularly at the delta-opioid receptor (4 orders of magnitude), but also at the mu-opioid receptor, which led to large differences (3 orders of magnitude) in receptor selectivity. For example, [(2S,3S)-beta-MePhe4]DPDPE (2) is 1800-fold selective in binding to the delta vs mu-receptor, making it one of the most selective delta-opioid receptor ligands in the enkephalin series as assessed by the rat brain binding assay, whereas the corresponding (2R,3R)-beta-Me-p-NO2phe-containing analogue 9 is only 4.5-fold selective (nonselective) in this same assay. On the other hand, in the bioassay systems, [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (5) is more potent than DPDPE and 8800-fold selective for the MVD (delta-receptor) vs the GPI (mu-receptor), making it the most highly selective ligand in this series for the delta-opioid receptor on the basis of these bioassays. In these assay systems, the (2R,3S)-beta-MePhe4-containing analogue 5 had very weak potency and virtually no receptor selectivity (4.4-fold). These results demonstrate that topographical modification alone in a conformationally restricted peptide ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity and suggest that this approach may have general application to peptide ligand design.

  DOI：

  10.1021/jm00110a010
• 作为产物：
  描述：

  马尿酸 在 palladium on activated charcoal lead(IV) acetate 、 盐酸 、 3,5-dimethylphenyl carbamate 、 amylose 10-undecenoate 、 氢溴酸 、 氢气 、 乙酸酐 、 溶剂黄146 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 氯仿 、 乙酸乙酯 、 异丙醇 、 甲苯 为溶剂， 反应 64.5h， 生成 (2S,3S)-methylphenylalanine
  参考文献：
  名称：

  苏式和赤式-β-甲基苯基丙氨酸的高效立体异构合成。半制备型HPLC拆分每个外消旋对

  摘要：

  受限氨基酸（βMe）Phe的苏式和赤式非对映异构体可以通过三步合成法从2-苯基-4（α-苯基亚乙基）-5（4 H）的相应Z和E异构体以多克级分别获得）-恶唑酮。5（4 H）-恶唑酮可容易地从苯乙酮和马尿酸获得。β-甲基苯丙氨酸的四个对映体纯异构体，（2 R，3 R）-（βMe）Phe，（2 S，3 S）-（βMe）Phe，（2 R，3 S）-（βMe）Phe和（ 2 S，3 R）-（βMe）Phe已通过HPLC拆分外消旋母体苏式（或赤式）-2-苯甲酰胺-3-苯基丁酸甲酯制备。

  DOI：

  10.1016/j.tet.2003.11.044

文献信息

• Catalytic Asymmetric Hydrogenation of<b><i>α</i></b>-(Acetamido)acrylates Using TRAP Trans-Chelating Chiral Bisphosphine Ligands: Remarkable Effects of Ligand<b><i>P</i></b>-Substituent and Hydrogen Pressure on Enantioselectivity
  作者：Ryoichi Kuwano、Masaya Sawamura、Yoshihiko Ito

  DOI：10.1246/bcsj.73.2571

  日期：2000.11

  β-substituent and the ligand P-substituent as well as decreasing hydrogen pressure. The selectivity for the (R)-product in the reaction with EtTRAP-rhodium catalyst at 60 °C and 0.5 kg cm-2 of hydrogen pressure was as follows: R = H, 96% ee; R = Me, 92% ee; R = Ph, 77% ee; R = i-Pr, 57% ee. The remarkable steric and pressure effects caused a dramatic reversal of enantioselectivity in the reaction of methyl

  用 [Rh(cod)2]BF4 和反式螯合手性双膦配体 (S,S)-2,2'-双 [( R)-1-(二烷基膦基)乙基]-1,1'-二茂铁[(R,R)-(S,S)-TRAPs]。在β-未取代或β-单取代的α-(乙酰氨基)丙烯酸酯[(E)-RCH=C(NHAc)CO2Me]的反应中，(R)-氢化产物的选择性随着底物β-空间需求的降低而增加取代基和配体 P 取代基以及降低氢压。在 60 °C 和 0.5 kg cm-2 氢气压力下与 EtTRAP-铑催化剂反应的 (R)-产物的选择性如下：R = H，96% ee；R = Me，92% ee；R = Ph，77% ee；R = i-Pr，57% ee。显着的空间和压力效应导致 2-(N-乙酰氨基) 肉桂酸甲酯 (R = Ph) 反应中对映选择性的显着逆转。例如，在 60 °C 和 0.1 kg cm-2 氢气压力下使用 EtTRAP 的选择性为 87%
• Asymmetric synthesis of unusual amino acids: An efficient synthesis of optically pure isomers of β-methylphenylalanine.
  作者：Ramalinga Dharanipragada、Katia VanHulle、Anne Bannister、Soaring Bear、Lisa Kennedy、Victor J Hruby

  DOI：10.1016/s0040-4020(01)81570-2

  日期：1992.6

  These acids were attached to the appropriate - or -auxiliary (a 4-phenylmethyl-2-oxazolidinone) to give a 3′-phenylbutanoyl-4-phenylmethyl-2-oxazolidinone. Asymmetric bromination was accomplished via the ciral imide enolate bromination methodology of Evans and co-workers (J. Am. Chem. Soc.1990112, 4011-40). Evidence for asymmetric induction was obtained from the X-ray structure of one of the intermediate

  许多α-氨基酸的非对映体β-氢的取代为肽结构的三维形貌控制提供了一种方法。需要氨基酸的不对称合成来促进这些研究。β-甲基苯丙氨酸，（2S，3S）-，（2R，3R）-，（2S，3R）-和（2R，3S）-β-甲基苯丙氨酸的所有四个单独的异构体均以高光学纯度合成。通过选择起始材料（+）-或（-）-3-苯基丁酸来设定β中心的立体化学。将这些酸与适当的-或-辅助的（4-苯基甲基-2-恶唑烷酮）连接，得到3'-苯基丁酰基-4-苯基甲基-2-恶唑烷酮。不对称溴化是通过Evans和同事的柠檬酰亚胺烯醇盐溴化方法完成的（J.Am. 化学 Soc。1990年112，4011-40）。从中间体溴化物之一的X射线结构获得了不对称诱导的证据。使用四甲基胍叠氮化物通过S N 2置换将溴化物转化为非对映异构叠氮化物。通过催化水解回收手性助剂后，通过在10％Pd / C上催化氢化获得手性氨基酸。所有四种异构体均以95：5至99：1的对映体纯度获得。
• Asymmetric synthesis of unusual amino acids: Synthesis of optically pure isomers of β-methylphenylalanine
  作者：Ramalinga Dharanipragada、Ernesto Nicolas、Geza Toth、Victor J. Hruby

  DOI：10.1016/s0040-4039(01)93366-0

  日期：1989.1

  All the four individual isomers of β-methylphenylalanine have been synthesized in very high optical purities by utilizing in part the chiral imide enolate bromination methodology of Evans and co-workers.

  β-甲基苯丙氨酸的所有四个单独的异构体都是通过部分地利用Evans和他的同事们的手性酰亚胺烯醇式溴化方法合成的，具有很高的光学纯度。
• Development of a Model for the .delta. Opioid Receptor Pharmacophore. 2. Conformationally Restricted Phe3 Replacements in the Cyclic .delta. Receptor Selective Tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13)
  作者：Henry I. Mosberg、John R. Omnaas、Andrei Lomize、Deborah L. Heyl、Ian Nordan、Carol Mousigian、Peg Davis、Frank Porreca

  DOI：10.1021/jm00051a016

  日期：1994.12

  properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which the alpha carbon of the Phe3 replacement has L-stereochemistry display high affinity for delta receptors with the (2S

  δ阿片受体选择性四肽Tyr-c [D-Cys-Phe-D-Pen] OH（JOM-13）类似物的体外药理特性和构象特征，其中Phe3残基被四种立体异构体中的每一种取代研究了β-甲基苯丙氨酸（β-MePhe）的含量。Phe3替代的α碳具有L-立体化学的两个类似物都显示出对δ受体的高亲和力，（2S，3S）-MePhe3类似物的亲和力比（2S，3R）-MePhe3非对映异构体高约8倍。令人惊讶地，残基3中具有D-立体化学的一种类似物，（2R，3R）-MePhe3类似物也对δ受体显示出高亲和力，并且对该受体具有极高的选择性。在小鼠输精管（MVD）和豚鼠回肠（GPI）平滑肌生物测定中，所有类似物都是激动剂，显示的MVD和GPI效能分别与其delta和mu阿片受体亲和力一致 使用β-MePhe替代Phe3是基于以下愿望：通过以β-甲基取代基的形式施加空间旋转约束来减少Phe3侧链的构象柔性，并由此推导
• Synthesis of the Methyl Ester of Tritium-labeled AK-toxin I, a Host-specific Toxin Produced by<i>Alternaria alternata</i>Japanese Pear Pathotype
  作者：Masakazu OKADA、Hisashi MIYAGAWA、Tamio UENO

  DOI：10.1271/bbb.63.1253

  日期：1999.1

  AK-toxin I, a host-specific toxin to Japanese pear (Pyrus serotina), was synthesized as its methyl ester from three precursor fragments: conjugated diene-carboxylic acid, chiral epoxyalcohol and β-methylphenylalanine. The epoxyalcohol fragment was derived from D-fructose, in which effective homologation of the hemiacetal carbon to alkyne by using dimethyl 1-diazo-2-oxopropylphosphonate was the key

  AK-毒素I是日本梨（Pyrus serotina）的一种宿主特异性毒素，是由其三个前体片段（共轭二烯-羧酸，手性环氧醇和β-甲基苯基丙氨酸）合成的甲酯形式的。环氧醇片段衍生自D-果糖，其中通过使用1-重氮-2-氧代丙基膦酸二甲酯使半缩醛碳有效同化为炔烃是关键反应。通过重复的Wittig反应制备二烯-羧酸片段，并通过Stille反应将其与环氧醇片段结合。用立体化学纯的β-甲基苯基丙氨酸片段酯化合并的产物，得到目标化合物。该方法用于制备tri标记的AK毒素I的甲酯，其比放射性为213 GBq / mmol。