L-3,3-diphenylalanine hydrochloride | 138662-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: L-3,3-diphenylalanine hydrochloride
• 英文别名: (2S)-3,3-Diphenylalanine hydrochloride；(S)-2-Amino-3,3-diphenylpropanoic acid hydrochloride；(2S)-2-amino-3,3-diphenylpropanoic acid;hydrochloride
• CAS: 138662-62-1
• 化学式: C₁₅H₁₅NO₂*ClH
• 分子量: 277.751
• InChiKey: SKIHATSEIBREBX-UQKRIMTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.65
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  63.3
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 L-3,3-diphenylalanine hydrochloride 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 以86%的产率得到N-Boc-3,3-二苯基-L-丙氨酸
  参考文献：
  名称：

  Asymmetric synthesis of L-diphenylalanine and L-9-fluorenylglycine via room temperature alkylations of a sultam-derived glycine imine

  摘要：

  L-diphenylalanine and L-9-fluorenylglycine were prepared from a sultam-derivated glycine imine 3 via room temperature-asymmetric-alkylation/ hydrolysis/mild-sultam-clivage. The L-configuration was ascertained using an X-ray analysis of the alkylation product 4b.

  DOI：

  10.1016/0040-4039(91)80217-t
• 作为产物：
  描述：

  (4S,5R)-3-(3,3-Diphenyl-propionyl)-4-methyl-5-phenyl-oxazolidin-2-one 在 palladium on activated charcoal 盐酸 、 lithium hydroxide 、 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 双氧水 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 水 为溶剂， -78.0 ℃ 、344.73 kPa 条件下， 反应 21.03h， 生成 L-3,3-diphenylalanine hydrochloride
  参考文献：
  名称：

  Chiral cynthesis of D- and L-3,3-diphenylalanine (DIP), unusual α-amino acids for peptides of biological interest

  摘要：

  The asymmetric syntheses of D-(R)-(-)- and L-(S)-(+)-3,3-diphenylalanine (Dip)

  DOI：

  10.1016/s0040-4039(00)92070-7

文献信息

• Cobalt-mediated alkylation of (4R) and (4S)-3-acetoacetyl-4-benzyloxazolidin-2-ones. Preparation of enantiopure diphenylmethyl-, 9-fluorenyl- and (1-adamantyl)glycines
  作者：Nicanor Gálvez、Marcial Moreno-Mañas、Adelina Vallribera、Elies Molins、Araceli Cabrero

  DOI：10.1016/0040-4039(96)01322-6

  日期：1996.8

  The Co(II) complexes of (4R) and (4S)-3-acetoacetyl-4-benzyloxazolidin-2-ones are alkylated diastereoselectively with diphenylmethyl, 9-fluorenyl, and 1-adamantyl bromide. The resulting products are converted into enantiopure α-substituted glycines. Similar results are obtained by alkylation of the free acetoacetyloxazolidinones under Co(II)-catalysis.

  （4 R）和（4 S）-3-乙酰乙酰基-4-苄基恶唑烷丁-2-酮的Co（II）配合物被二苯甲基，9-芴基和1-金刚烷基溴化物非对映选择性地烷基化。将所得产物转化为对映体纯的α-取代的甘氨酸。在Co（II）催化下，通过将游离的乙酰乙酰基恶唑烷酮进行烷基化，可获得相似的结果。
• Process for the preparation of D(-) and L(+)-3,3-diphenylalanine and
  申请人：Warner-Lambert Company

  公开号：US05198548A1

  公开（公告）日：1993-03-30

  A process for the preparation of D(-) and L(+)-3,3-diphenylalanine and D(-) and L(+)-substituted 3,3-diphenylalanines is described where N-protected DL-3,3-diphenylalanine or N-protected-DL-substituted 3,3-diphenylalanine are treated with (-)cinchonidine and the resulting salt resolved into the desired enantiomers, as well as derivatives thereof and valuable intermediates used in the process.

  本发明提供一种制备D(-)和L(+)-3,3-二苯基丙氨酸以及D(-)和L(+)-取代的3,3-二苯基丙氨酸的方法，其中将N-保护的DL-3,3-二苯基丙氨酸或N-保护的DL-取代的3,3-二苯基丙氨酸与(-)奎宁啶处理，并将得到的盐分离成所需的对映体，以及在该过程中使用的其衍生物和有价值的中间体。
• Aromatic compounds, pharmaceutical compositions containing them and
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05629347A1

  公开（公告）日：1997-05-13

  Compounds of formula (I), and salts and prodrugs thereof, wherein Q is R.sup.9 CR.sup.10 R.sup.11 or CH.sub.2 R.sup.9 CR.sup.10 R.sup.11 where R.sup.9 is H or OH and R.sup.10 and R.sup.11 are optionally substituted phenyl, optionally substituted benzyl, C.sub.5-7 cycoalkyl or (C.sub.5-7 cycloalkyl)methyl; R.sup.1 and R.sup.2 are H, optionally substituted C.sub.1-6 alkyl, optionally substituted phenyl(C.sub.1-4 alkyl), C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, COR.sup.a, COOR.sup.a, COC.sub.1-6 alkylhalo, COC.sub.1-6 alkylNR.sup.a R.sup.b, CONR.sup.12 C.sub.1-6 alkylCONR.sup.a R.sup.b, CONR.sup.a R.sup.b, or SO.sub.2 R.sup.a, or R.sup.1 and R.sup.2 together form a chain (CH.sub.2).sub.q optionally substituted by oxo where one methylene group may optionally be replaced by O or NR.sup.x ; R.sup.3 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; R.sup.4 is optionally substituted phenyl(C.sub.1-3 alkyl); X and Y are H, or X and Y together are .dbd.O; and Z is O, S, or NR.sup.7 ; are tachykinin antagonists. They and compositions thereof are useful in therapy.

  化合物的公式(I)及其盐和前药，其中Q是R.sup.9 CR.sup.10 R.sup.11或CH.sub.2 R.sup.9 CR.sup.10 R.sup.11，其中R.sup.9是H或OH，R.sup.10和R.sup.11是可选取代的苯基，可选取代的苄基，C.sub.5-7 环烷基或（C.sub.5-7 环烷基）甲基; R.sup.1和R.sup.2是H，可选取代的C.sub.1-6烷基，可选取代的苯基（C.sub.1-4烷基），C.sub.2-6烯基，C.sub.2-6炔基，COR.sup.a，COOR.sup.a，COC.sub.1-6烷基卤素，COC.sub.1-6烷基NR.sup.aR.sup.b，CONR.sup.12 C.sub.1-6 烷基CONR.sup.aR.sup.b，CONR.sup.aR.sup.b或SO.sub.2R.sup.a，或R.sup.1和R.sup.2一起形成链（CH.sub.2）.sub.q，其中可以用氧代替一个亚甲基，其中R.sup.x是H或C.sub.1-6烷基；R.sup.3是H，C.sub.1-6烷基或C.sub.2-6烯基；R.sup.4是可选取代的苯基（C.sub.1-3烷基）；X和Y是H，或X和Y一起是.dbd.O；Z是O，S或NR.sup.7；都是缓激肽拮抗剂。它们及其组合物在治疗中有用。
• 2/3-(heterocyclic alkyl
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05494926A1

  公开（公告）日：1996-02-27

  Compounds of formula (I), and salts and prodrugs thereof, wherein Q represents phenyl or benzhydryl; X and Y each represent H or X and Y together form a group =0; Z is O, S or NR.sup.8 (R.sup.8 is H or C.sub.1-6 alkyl); R.sup.1 is H, optionally substituted C.sub.1-6 alkyl, phenyl(C.sub.1-4 alkyl), C.sub.2-6 alkylene, COR.sup.a, COOR.sup.a, CONHR.sup.a, COC.sub.1-4 alkylNR.sup.a R.sup.b, or CONR.sup.a C.sub.1-4 alkylCONR.sup.a R.sup.b ; R.sup.2 is C.sub.1-4 alkyl substituted by an optionally substituted aromatic heterocycle; R.sup.3 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; R.sup.4 is H, C.sub.1-6 alkyl or optionally substituted phenyl; R.sup.5 represents optionally substituted phenyl; and q is 0, 1, 2 or 3; are tachykinin antagonists useful in therapy. ##STR1##

  式(I)的化合物、盐和前药，其中Q代表苯或苯甲基；X和Y分别代表H或X和Y组合形成=0基团；Z为O、S或NR.sup.8（R.sup.8为H或C.sub.1-6烷基）；R.sup.1为H、可选择性取代的C.sub.1-6烷基、苯基（C.sub.1-4烷基）、C.sub.2-6烷基、COR.sup.a、COOR.sup.a、CONHR.sup.a、COC.sub.1-4烷基NR.sup.a R.sup.b或CONR.sup.a C.sub.1-4烷基CONR.sup.a R.sup.b；R.sup.2为C.sub.1-4烷基，其上取代有可选择性取代的芳香杂环；R.sup.3为H、C.sub.1-6烷基或C.sub.2-6烯基；R.sup.4为H、C.sub.1-6烷基或可选择性取代的苯基；R.sup.5代表可选择性取代的苯基；q为0、1、2或3；这些化合物是治疗中有用的缓激肽拮抗剂。
• Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
  作者：Hubert Josien、Solange Lavielle、Alie Brunissen、Monique Saffroy、Yvette Torrens、Jean-Claude Beaujouan、Jacques Glowinski、Gerard Chassaing

  DOI：10.1021/jm00037a009

  日期：1994.5

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.