(3S)-3-{[(苄氧基)羰基]氨基}-3-苯丙酸 | 14441-08-8

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: (3S)-3-{[(苄氧基)羰基]氨基}-3-苯丙酸
• 中文别名: (S)-N-Z-3-氨基3-苯基丙酸
• 英文名称: Z-D-β-homophenylglycine
• 英文别名: N-(benzyloxycarbonyl)-D-3-amino-3-phenylpropionic acid；N-(Benzyloxycarbonyl)-3(S)-phenyl-β-alanine；N-Cbz-(3S)-β-phenylalanine；(3S)-N-(benzyloxycarbonyl)-3-amino-3-phenylpropanoic acid；(S)-β-[[(phenylmethoxy)carbonyl]amino]-benzenepropanoic acid；Benzyloxycarbonyl-L-β-amino-β-phenyl-propionsaeure；D-β-(Benzyloxycarbonylamino)-β-phenylpropionsaeure；(S)-3-(((benzyloxy)carbonyl)amino)-3-phenylpropanoic acid；N-Cbz-(3S)-β-Phe-OH；(3S)-3-phenyl-3-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 14441-08-8
• 化学式: C₁₇H₁₇NO₄
• 分子量: 299.326
• InChiKey: POJLWVWXBAHGGO-HNNXBMFYSA-N

物化性质

• 熔点：
  121.5-122.5 °C
• 沸点：
  507.9±50.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (3S)-3-{[(苄氧基)羰基]氨基}-3-苯丙酸 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 苯 为溶剂， 反应 5.5h， 生成 (3S)-3-氨基-3-苯基丙酸叔丁酯
  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：

  (S)-4-benzyl-3-phenylacetyl-2-oxazolidinone 在 lithium hydroxide 、 二甲基硫 、 二苯基磷酸 、 双氧水 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 、 三氟乙酸 为溶剂， 反应 13.0h， 生成 (3S)-3-{[(苄氧基)羰基]氨基}-3-苯丙酸
  参考文献：
  名称：

  A General Method for the Synthesis of Enantiomerically Pure β-Substituted, β-Amino Acids through α-Substituted Succinic Acid Derivatives

  摘要：

  A general procedure for the synthesis of enantiopure beta-substituted, beta-amino acids is presented. Alkylation of the sodium enolates derived from chiral N-acyloxazolidinone imides 2 (R = Me, i-Pr, t-Bu, Ph, Bn) with tert-butyl bromoacetate afforded the 2-substituted succinate derivatives 3 in good yields (82-89%) and with high selectivity (greater than or equal to 93:7). Following hydrolysis, Curtius rearrangement of the resulting carboxylic acid provided the enantiopure benzyloxycarbonyl (Cbz)-protected beta-amino esters 6 in good yields (74-79%).

  DOI：

  10.1021/jo990756k

文献信息

• Thiadiazole amide MMP inhibitors
  申请人：——

  公开号：US05830869A1

  公开（公告）日：1998-11-03

  The present invention provides novel thiadiazole amide derivatives represented by formula I ##STR1## The compounds of the present invention inhibit various enzymes from the matrix metalloproteinase family, predominantly stromelysins, and hence are useful for the treatment of matrix metallo endoproteinase diseases such as osteoarthritis, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis, periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration, inflammation and other diseases related to connective tissue degradation.

  本发明提供了由式I表示的新型噻二唑酰胺衍生物。本发明的化合物抑制来自基质金属蛋白酶家族的各种酶，主要是胶原酶，因此对于治疗基质金属蛋白酶疾病如骨关节炎、类风湿性关节炎、化脓性关节炎、骨质疏松症如骨质疏松症、肿瘤转移、牙周炎、牙龈炎、角膜溃疡、皮肤溃疡、胃溃疡、炎症和其他与结缔组织降解相关的疾病具有用处。
• Diastereoselective Cationic Tandem Cyclizations to <i>N</i>-Heterocyclic Scaffolds:  Total Synthesis of (−)-Dysibetaine PP
  作者：Denis R. IJzendoorn、Peter N. M. Botman、Richard H. Blaauw

  DOI：10.1021/ol052598r

  日期：2006.1.1

  [reaction: see text] Herein, we report a short and diastereoselective synthesis of the natural product (-)-dysibetaine PP. The key step in the synthetic sequence is a novel highly diastereoselective tandem-cyclization reaction of an enantiomerically pure dipeptide. This cyclization methodology is applied in the synthesis of a broader range of N-heterocyclic scaffolds.

  [反应：见正文]在此，我们报道了天然产物（-）-dysibetaine PP的短而非对映选择性合成。合成序列中的关键步骤是对映体纯的二肽的新型高度非对映选择性串联环化反应。这种环化方法学可用于合成范围更广的N杂环支架。
• Analogs of 2'(3')-O-L-phenylalanyladenosine as substrates and inhibitors of ribosomal peptidyltransferase
  作者：Jiri Zemlicka、Aruna Bhuta、Prakash Bhuta

  DOI：10.1021/jm00356a010

  日期：1983.2

  The chemical syntheses of 2'(3')-O-(L-3-amino-3-phenylpropionyl)adenosine (2e), the corresponding D stereoisomer 2f, 2'(3')-O-(DL-phenylglycyl)adenosine (2g), 2'(3')-O-(N-benzylglycyl)adenosine (2h), and 9(2-O-L-phenylalanyl-beta-D-xylofuranosyl)adenine (3b) are described. Compounds 2e-h were obtained by acylation of 5'-O-(4-methoxytrityl)adenosine with the appropriate N-benzyloxycarbonyl or N-tert-butoxycarbonyl

  2'（3'）-O-（L-3-氨基-3-苯基丙酰基）腺苷（2e），相应的D立体异构体2f，2'（3'）-O-（DL-苯基甘氨酰基）腺苷的化学合成描述了（2g），2'（3'）-O-（N-苄基甘氨酰基）腺苷（2h）和9（2-OL-苯丙氨酰基-β-D-木呋喃糖基）腺嘌呤（3b）。通过将5'-O-（4-甲氧基三苯甲基）腺苷与合适的N-苄氧基羰基或N-叔丁氧基羰基氨基酸与吡啶中的二环己基碳二亚胺酰化，获得化合物2e-h。N-（苄氧羰基）-D-苯基甘氨酸的相应反应导致氨酰基残基（化合物2c和2g）几乎完全消旋。随后的色谱分离和中间体2a-d的脱保护得到所需的目标衍生物2e-h。产物3b是通过类似的9-（3，将5-O-异亚丙基-β-D-呋喃呋喃糖基）腺嘌呤与N-（苄氧基羰基）-L-苯丙氨酸一起，然后脱保护。讨论了立体异构体2a和2b的2'和3'异构体的NMR光谱。化合物2g和3b都是大肠杆菌核糖体肽基转移
• Efficient synthesis of β’-amino-α,β-unsaturated ketones
  作者：Isabelle Abrunhosa-Thomas、Aurélie Plas、Nishanth Kandepedu、Pierre Chalard、Yves Troin

  DOI：10.3762/bjoc.9.52

  日期：——

  A general and simple procedure to access chiral β'-amino-α,β-enones, in seven steps, from an α,β unsaturated ester has been described. The use of a Horner–Wadsworth–Emmons reaction as a key step for generating the β'-amino-α,β-enones, permits access to a range of substrates under mild conditions and in moderate to high yield.

  一种通用且简单的程序，通过七个步骤，从α，β不饱和酯中制备手性β'-氨基-α，β-烯酮已经被描述。使用Horner–Wadsworth–Emmons反应作为生成β'-氨基-α，β-烯酮的关键步骤，可以在温和条件下以中等至高收率获得一系列底物。
• Development of a Bulk Enabling Route to Maraviroc (UK-427,857), a CCR-5 Receptor Antagonist
  作者：Sarah J. Haycock-Lewandowski、Alexander Wilder、Jens Åhman

  DOI：10.1021/op8000614

  日期：2008.11.21

  A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3, 4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation

  提出了能够合成CCR-5受体拮抗剂Maraviroc（UK-427,857）（1）的物质。三个关键片段的合成，β氨基酯3，4,4- difluorohexanecarboxylic酸（2），和1,3,4-三唑基取代的莨菪烷片段4中描述。对这些片段的偶联策略进行了讨论和描述，包括合成挑战，保护策略，杂质生成以及最终发展成1的路线的最终放大。