(S)-3-benzyloxycarbonylamino-4-phenylbutyric acid | 26250-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-3-benzyloxycarbonylamino-4-phenylbutyric acid
• 英文别名: (S)-3-(benzyloxycarbonylamino)-4-phenylbutanoic acid；Z-L-β-homophenylalanine；(S)-3-(((Benzyloxy)carbonyl)amino)-4-phenylbutanoic acid；(3S)-4-phenyl-3-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 26250-86-2
• 化学式: C₁₈H₁₉NO₄
• 分子量: 313.353
• InChiKey: WUIQVOMIYLNNEC-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  (S)-3-benzyloxycarbonylamino-4-phenylbutyric acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 苯 为溶剂， 反应 6.5h， 生成 (E)-3-((S)-1-tert-Butoxycarbonylmethyl-2-phenyl-ethylcarbamoyl)-4-phenyl-but-3-enoic acid ethyl ester
  参考文献：
  名称：

  New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties

  摘要：

  In order to improve the in vivo protection of enkephalins from enzymatic degradation, a new series of inhibitors derived from kelatorphan [HONHCOCH2CH(CH2Ph)CONHCH(CH3)COOH], the first-described complete inhibitor of enkephalin metabolism, were designed by modification of the C-terminal amino acid. The progressive lengthening of the chain of this residue shows that a beta-alanine seems to be the best basic model for the conception of such types of compounds. On the other hand, the methylation of the amide bond, which is well accepted by aminopeptidase N (EC 3.4.11.2) and dipeptidylaminopeptidase, induced a significant loss of affinity for neutral endopeptidase -24.11. Starting from these data, compounds containing a variously substituted beta-alanine residue and corresponding to the general formula HONHCOCH2CH(CH2Ph)CONHCH(R1)CH(R2)COOH were synthesized. All these molecules inhibit neutral endopeptidase -24.11 and dipeptidylaminopeptidase in the nanomolar range, and those containing an aromatic chain (compound 7A, R1 = CH2Ph,R2 = H, and compound 8A, R1 = Ph, R2 = H) inhibit the biologically relevant aminopeptidase N, with IC50's around 10(-8) M. Intracerebroventricular injection in mice of these multienzyme inhibitors produced an efficient and naloxone-reversible analgesic response (hot plate test): compounds 7A and 8A were shown to be more potent than kelatorphan in increasing the jump latency time, in agreement with their in vitro properties, and these new compounds were found to increase the forepaw lick latency, a reflex considered as a typical morphine response.

  DOI：

  10.1021/jm00127a017
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨酸 在 silver trifluoroacetate 、 氯甲酸乙酯 作用下， 生成 (S)-3-benzyloxycarbonylamino-4-phenylbutyric acid
  参考文献：
  名称：

  旋光性β-氨基酸N-羧基氢化物的合成。

  摘要：

  已经开发了通过使用三溴化磷将Nβ-Boc或Nβ-Cbzβ-氨基酸环化来一般合成旋光性β-氨基酸N-羧基酸酐（β-NCA）的方法。β-NCA的形成已通过光谱法以及β-高丙氨酸-N-羧基酸酐的X射线结构测定得到了证实。β-NCA分子可以以高收率聚合，以产生在溶液中采用稳定手性构象的旋光性聚（β-肽）。例如，通过L-β-高苯丙氨酸-N-羧基酸酐的聚合来合成螺旋低聚物（L-β-高苯丙氨酸）。

  DOI：

  10.1021/ol000122w

文献信息

• Synthesis of diazoketones derived from α-amino acids; problem of side reactions
  作者：Krystyna Plucińska、Bogdan Liberek

  DOI：10.1016/s0040-4020(01)81643-4

  日期：1987.1

  Optimum conditions of synthesis of eight diazoketones derived from optically active N-(t-butyloxycarbonyl)- and N-benzyloxycarbonylamino acids have been described. The problem of formation of by-products during Arndt-Eistert synthesis of β-homoamino acids at the stage of reaction of mixed anhydride with a weak nucleophile-diazomethane - has been discussed.

  已经描述了合成八种衍生自光学活性的N-（叔丁氧羰基）-和N-苄氧羰基氨基酸的重氮酮的最佳条件。讨论了在混合酸酐与弱亲核试剂-重氮甲烷反应的阶段，在Arndt-Eistert合成β-均氨基酸过程中形成副产物的问题。
• Convenient in situ synthesis of nonracemic N-protected β-amino aldehydes from β-amino acids. Applications in Wittig reactions and heterocycle synthesis
  作者：Simon B. Davies、M.Anthony McKervey

  DOI：10.1016/s0040-4039(98)02573-8

  日期：1999.2

  N-Z-γ-amino alcohols derived from nonracemic β-amino acids are smoothly oxidised by manganese dioxide in acetonitrile to afford aldehydes which can be trapped in situ in Wittig reactions with carbonyl-substituted phosphoranes. The application of this methodology to the synthesis of the alkaloids (S)-(+)-N-BOC-coniie, (S)-(−)-coniceine and a pipecoline precursor is described.

  源自非外消旋β-氨基酸的N - Z -γ-氨基醇在乙腈中被二氧化锰平滑氧化，得到醛，这些醛可在Wittig反应中与羰基取代的磷烷原位捕获。描述了该方法在生物碱（S）-（+）- N -BOC-coniie，（S）-（-）-coniceine和胡椒碱前体的合成中的应用。
• Synthesis of a .BETA.-Tetrapeptide Analog as a Mother Compound for the Development of Matrix Metalloproteinase-2-Imaging Agents
  作者：Takahiro Mukai、Noriko Suganuma、Kenta Soejima、Junichi Sasaki、Fumihiko Yamamoto、Minoru Maeda

  DOI：10.1248/cpb.56.260

  日期：——

  Matrix metalloproteinase-2 (MMP-2) is an attractive target for the diagnosis of cancer and atherosclerosis in nuclear imaging. A cyclic decapeptide, cCTTHWGFTLC (cCTT), has been used as the mother compound for the development of MMP-2-imaging agents with high potency and selectivity. Most of radiolabeled derivatives of cCTT currently developed for in vivo studies of MMP-2, however, suffer from low accumulation in the target tissues, such as tumors. For enhanced in vivo stability and tissue penetration, we designed a linear β-tetrapeptide analog, H-β3-Phe-β-Ala-β3-Trp-β3-His-OH (1), to mimic cCTT. The component β-amino acids were prepared by reduction of N-protected α-amino acid methyl esters to the alcohols, followed by conversion into the cyanides, and subsequent hydrolysis. Compound 1 was obtained from these β-amino acids by the conventional solution method. In MMP-2 inhibition assay, compound 1 displayed desirably significant inhibition, which was comparable to cCTT. These findings suggest that compound 1 may serve as a mother compound in the design and development of in vivo MMP-2-imaging agents.

  基质金属蛋白酶-2(MMP-2)是核成像中诊断癌症和动脉粥样硬化的理想靶点。环状十肽cCTTHWGFTLC(cCTT)已被用作开发高效能和选择性的MMP-2成像剂的母体化合物。然而，目前开发的大多数cCTT放射性标记衍生物在体内研究MMP-2时，在目标组织如肿瘤中的积累较低。为了提高体内稳定性和组织穿透性，我们设计了一种线性β-四肽类似物H-β3-Phe-β-Ala-β3-Trp-β3-His-OH(1)，以模拟cCTT。这些β-氨基酸成分是通过将N-保护的α-氨基酸甲酯还原为醇，然后转化为氰化物，最后进行水解得到的。化合物1是通过传统的溶液方法从这些β-氨基酸制备的。在MMP-2抑制测定中，化合物1显示出显著的抑制效果，与cCTT相当。这些发现表明，化合物1可能在设计和发展体内MMP-2成像剂中作为母体化合物。
• Effective Methods for the Synthesis ofN-Methylβ-Amino Acids from All Twenty Commonα-Amino Acids Using 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones
  作者：Andrew B. Hughes、Brad E. Sleebs

  DOI：10.1002/hlca.200690235

  日期：2006.11

  N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to

  应用N-甲基β-氨基酸通常是潜在合成具有生物活性的修饰的肽和其他寡聚体的应用。先前的工作强调了1，3-恶唑烷-5-酮的还原裂解以合成N-甲基α-氨基酸。从α-氨基酸开始，使用两种方法来制备相应的N-甲基β-氨基酸。首先，α -氨基酸转化为Ñ甲基α -氨基酸由所谓的“-1,3-恶唑-5-酮的策略”，将它们再由同系阿恩特-艾斯特方法，得到Ñ-protected Ñ -甲基β -氨基酸选自20种常见衍生α -氨基酸。这些化合物的制备产率为23–57％（相对于N-甲基α-氨基酸）。在第二种方法中，可以通过Arndt–Eistert方法将12个N保护的α-氨基酸直接同源，然后将所得的β-氨基酸以30–45％的产率转化为1,3-恶二嗪-6-酮。 。最后，还原裂解以41–63％的收率提供了所需的N-甲基β-氨基酸。
• Homologation of α-amino acids to β-amino acids using Boc₂O
  作者：Ganga-Ramu Vasanthakumar、Basanagoud S. Patil、Vommina V. Suresh Babu

  DOI：10.1039/b204652k

  日期：——

  The use of Boc2O as a coupling agent in the homologation of N-urethane protected-α-amino acid to its β-homomers by the Arndt–Eistert method is described. The homologation gives good yields without racemization. The use of Boc2O as a coupling agent not only allows the easy scale up of the process but also it is cost effective.

  在利用Arndt-Eistert方法将N-羟基脲保护的α-氨基酸同系化为其β-同系物的过程中，使用Boc2O作为偶联剂的方法已被描述。该同系化反应能够获得良好的产率，且不会发生消旋化。使用Boc2O作为偶联剂不仅使得过程易于放大，而且在成本方面也是经济有效的。