Z-D-叔丁基谷氨酸 | 51644-83-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 谷氨酸类衍生物
• 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
• 中文名称: Z-D-叔丁基谷氨酸
• 英文名称: N-(benzyloxycarbonyl)-D-glutamic acid γ-tert-butyl ester
• 英文别名: N-(benzyloxy)carbonyl-D-glutamic acid 5-tert-butyl ester；z-d-Glu(otbu)-oh；(2R)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 51644-83-8
• 化学式: C₁₇H₂₃NO₆
• 分子量: 337.373
• InChiKey: GLMODRZPPBZPPB-CYBMUJFWSA-N

物化性质

• 沸点：
  522.6±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• 稳定性/保质期：
  如果按照规定使用和储存，则不会分解，且没有已知的危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Z-D-Glu(otbu)-oh
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: Z-D-Glu(otbu)-oh
CAS number: 51644-83-8

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C17H23NO6
Molecular weight: 337.4

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-(benzyloxycarbonyl)-D-glutamic acid 5-tert-butyl ester 1-methyl ester	56877-41-9	C18H25NO6	351.4
  ——	tert-butyl (4R)-4-{[(benzyloxy)carbonyl]amino}-5-hydroxypentanoate	106930-52-3	C17H25NO5	323.389
  ——	N-benzyloxycarbonyl-D-glutamic acid	63648-73-7	C13H15NO6	281.265
  N-[苄氧羰基]-D-谷氨酸 1-甲基酯	N-(benzyloxycarbonyl)-D-glutamic acid 1-methyl ester	26566-11-0	C14H17NO6	295.292
  ——	Z-L-GluOMe	5672-83-3	C14H17NO6	295.292
  ——	(R)-2-(((benzyloxy)carbonyl)(methyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid	140837-98-5	C18H25NO6	351.4
  ——	tert-butyl (4S)-4-{[(benzyloxy)carbonyl]amino}pentanoate	475266-28-5	C17H25NO4	307.39
  ——	tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-carbamoylbutyrate	77340-94-4	C17H24N2O5	336.388
  ——	tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-cyanobutyrate	174488-19-8	C17H22N2O4	318.373
  ——	1-dimethylethyl 5-[[4-(4-cyanophenyl)butyl]amino]-5-oxo-4(R)-[[(phenylmethoxy)carbonyl]amino]pentanoate	151301-90-5	C28H35N3O5	493.603

反应信息

• 作为反应物：
  描述：

  Z-D-叔丁基谷氨酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-[苄氧羰基]-D-谷氨酸 1-甲基酯
  参考文献：
  名称：

  碳硅烷树枝状楔的合成及其在构建树枝状受体中的用途。

  摘要：

  已经开发了用于合成包含溴或胺作为焦点的碳硅烷楔的不同途径。这些新的构建基块可以构建各种核心功能化的碳硅烷树枝状聚合物。作为典型的例子，已经合成了直至第三代的含N，N′，N′-1，3，5-苯三甲酰胺核心（G1-G3）的碳硅烷树状大分子。已经研究了这类新型分子作为宿主分子，并且发现它们通过氢键相互作用与受保护的氨基酸结合为客体分子。对于较高年龄的树突状宿主，观察到缔合常数降低，这归因于结合位点所在的核周围的空间位阻增加。可以通过修饰碳硅烷树状大分子核心处的结合基序来调节树状主体分子的结合特性。当第三代N，N'，N''-1,3,5-三（L-丙氨酸）苯三甲酰胺核心功能化后，N-CBZ保护的谷氨酸1-甲酯（5）的缔合常数更高。与G3相比，碳硅烷树状聚合物（G3'）被用作主体分子。非对映异构体G3'.L-5（K = 295 M（-1））和G3'。（D-5）（2）（K = 236 M（-1））主宾的形成

  DOI：

  10.1039/b514583j
• 作为产物：
  描述：

  氯甲酸苄酯 、 D-谷氨酸-5-叔丁酯 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以47%的产率得到Z-D-叔丁基谷氨酸
  参考文献：
  名称：

  [EN] IMMUNOSTIMULATING AGENT
  [FR] AGENT IMMUNOSTIMULANT

  摘要：

  本发明旨在提供一种免疫刺激剂，其在免疫刺激效果方面优越，特别是作为疫苗佐剂有用的化合物，含有该化合物的药物组合物，含有该化合物和抗原的疫苗。本发明涉及一种免疫刺激剂，其至少包含下式(I)所表示的一种化合物：其中每个符号如描述中所定义，或其盐，或至少包含下式(II)所表示的一种化合物：其中每个符号如描述中所定义，或其盐。

  公开号：

  WO2017073797A1

文献信息

• Anthranilic acid-containing cyclic tetrapeptides: at the crossroads of conformational rigidity and synthetic accessibility
  作者：Dongyue Xin、Kevin Burgess

  DOI：10.1039/c6ob00693k

  日期：——

  contributes three atom units to main-chains, hence natural cyclic peptides can be 9, 12, 15, …. i.e. 3n membered-rings, where n is the number of amino acids. Cyclic peptides that are 9 or 12-membered ring compounds tend to be hard to prepare because of strain, while their one amino acid homologs (15-membered cyclic pentapeptides) are not conformationally homogeneous unless constrained by strategically placed

  肽中的每个氨基酸在主链上贡献三个原子单元，因此天然环肽可以是9、12、15等。即3个n元环，其中n是氨基酸数。9或12元环化合物的环肽由于应变而往往难以制备，而它们的一个氨基酸同源物（15元环五肽）在构象上不是均质的，除非受到策略性地放置的脯氨酸或D的约束-氨基酸残基。我们假设用刚性β-氨基酸取代环状四肽中的一种遗传编码氨基酸将使拟肽设计处于合成可及性和构象刚性之间的有用十字路口。因此，本研究探索了非脯氨酸含有13位环肽1的特征，该肽具有一个邻氨基苯甲酸（Anth）残基。制备了十二种这种类型的环状肽，并以此证明了固相和固相方法的可行性。产生的文库包含一套完整的四个非对映异构体，序列为1aaf（即，环-AlaAlaPhe Anth）。无一例外，这四种非对映异构体各自在溶液中采用一种主要的构象。基本上这些构象的特征是酰胺N – H向量在赤道平面的上方和下方起皱，并且使它们的N –原子近似指向极
• Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions
  申请人：Bristol-Myers Squibb Company

  公开号：US09308236B2

  公开（公告）日：2016-04-12

  The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

  本公开提供了一种新型的大环肽，可以抑制PD-1/PD-L1和PD-L1/CD80蛋白质相互作用，因此对改善包括癌症和传染病在内的各种疾病有用。
• TETRAHYDRONAPHTHALENE AND TETRAHYDROISOQUINOLINE DERIVATIVES AS ESTROGEN RECEPTOR DEGRADERS
  申请人：Arvinas, Inc.

  公开号：US20180155322A1

  公开（公告）日：2018-06-07

  The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，这些化合物可用作雌激素受体（目标蛋白）的调节剂。特别是，本公开涉及包含在一段至少有一种Von Hippel-Lindau配体、一种cereblon配体、凋亡抑制蛋白配体、小鼠双分钟同源2配体或其组合的双功能化合物，这些配体与相应的E3泛素连接酶结合，在另一端有一个与目标蛋白结合的部分，使得目标蛋白被置于泛素连接酶附近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白降解/抑制相关的广泛药理活性。可以通过本公开的化合物和组合物治疗或预防由目标蛋白聚集或积累引起的疾病或障碍。
• An Efficient Approach to Chiral C8/C9-Piperazino-Substituted 1,4-Benzodiazepin-2-ones as Peptidomimetic Scaffolds
  作者：Stefania Butini、Emanuele Gabellieri、Paul Brady Huleatt、Giuseppe Campiani、Silvia Franceschini、Margherita Brindisi、Sindu Ros、Salvatore Sanna Coccone、Isabella Fiorini、Ettore Novellino、Gianluca Giorgi、Sandra Gemma

  DOI：10.1021/jo8015456

  日期：2008.11.7

  a versatile approach to introduce cyclic, protonatable functionality at C8/C9. Introduction of the piperazine system at C8 and C9 gave access to a unique functionalization of the versatile benzodiazepine skeleton, broadening tailoring options on the benzofused side of the molecule, and the possibility of discovering novel peptidomimetics potentially able to modulate protein-protein interactions. Coupling

  干扰生物过程的一种有前途的方法是通过充当拟肽的小分子调节蛋白质-蛋白质相互作用。1,4-苯并二氮杂pine骨架已被广泛报道为模仿肽的致药系统。尽管已经公开了几种通往C6-8取代的苯并二氮杂卓的合成途径，但几乎没有报道在C9处被取代的1，4-苯并二氮杂卓。在这里，我们描述了一种通用的方法，可以在C8 / C9处引入循环的，可质子化的功能。在C8和C9引入哌嗪系统后，即可获得通用的苯并二氮杂skeleton骨架的独特功能化，拓宽了分子在苯并稠合侧的剪裁选择，并发现了可能调节蛋白质-蛋白质相互作用的新型肽模拟物。在温和条件下，将活化的氨基酸与反应性较弱的苯胺偶联，同时避免了外消旋作用，可轻松获得这些化合物。通过使用三苯基膦和六氯丙酮，在低温和无酸/碱的条件下利用酰氯的快速形成，可以实现有效的氨基酸活化。该方法成功地导致了高反应产率，没有产生外消旋作用（ee> 98％，如通过使用手性溶剂化剂所证明
• Structure-Activity Relationships of 13- and 14-Membered Cyclic Partial Retro-Inverso Pentapeptides Related to Enkephalin
  作者：Nam-Joo Hong

  DOI：10.5012/bkcs.2010.31.04.874

  日期：2010.4.20

  A series of 13- and 14-membered cyclic enkephalin analogs based on the moderately $\mu$ selective prototype compound Tyr-C[D-$A_2bu$-Gly-Phe-Leu] 8a were synthesized to investigate the structure-activity relationship. The modifications of sequence were mainly focused on two positions 3 and 5, critical for the selective recognition for $\mu$ and $\delta$ opioid receptors. The substitution of hydrophobic $Leu^5$ with hydrophilic $Asp^5$ derivatives led to Tyr-C[D-$A_2bu$-Gly-Phe-Asp(N-Me)] 7 and Tyr-C[D-Glu-Phe-gPhe-rAsp(O-Me)] 5, the peptides with a large affinity losses at both $\mu$ and $\delta$ receptors. The substitution of $Phe^3$ with $Gly^3$ led to Tyr-C[D-Glu-Gly-gPhe-rLeu] 3 and Tyr-C[D-Glu-Gly-gPhe-D-rLeu] 4, the peptides with large affinity losses at $\mu$ receptors, indicating the critical role of phenyl ring of $Phe^3$ for $\mu$ receptor affinities. One atom reduction of the ring size from 14-membered analogs Tyr-C[D-Glu-Phe-gPhe-(L and D)-rLeu] 6a, 6b to 13-membered analogs Tyr-C[D-Asp-Phe-gPhe-(L and D)-rLeu] 1, 2 reduced the affinity at both $\mu$ and $\delta$ receptors, but increased the potency in the nociceptive assay, indicating the ring constrain is attributed to high nociceptive potency of the analogs. For the influence of D- or L-chirality of $Leu^5$ on the receptor selectivity, regardless of chirality and ring size, all cyclic diastereomers displayed marked $\mu$ selectivity with low potencies at the $\delta$ receptor. The retro-inverso analogs display similar or more active at $\mu$ receptor, but less active at $\delta$ receptor than the parent analogs.

  一系列基于中等选择性的μ受体原型化合物Tyr-C[D--Gly-Phe-Leu] 8a的13和14成员环状类脑啡肽类似物被合成，以研究结构-活性关系。序列的修改主要集中在3和5位，这两位对于选择性识别μ和δ阿片受体至关重要。将疏水性Leu^5替换为亲水性Asp^5衍生物，导致Tyr-C[D--Gly-Phe-Asp(N-Me)] 7和Tyr-C[D-Glu-Phe-gPhe-rAsp(O-Me)] 5的合成，这些肽在μ和δ受体上的亲和力均大幅下降。将Phe^3替换为Gly^3，得到Tyr-C[D-Glu-Gly-gPhe-rLeu] 3和Tyr-C[D-Glu-Gly-gPhe-D-rLeu] 4，这些肽在μ受体上的亲和力显著下降，表明Phe^3的苯环在μ受体亲和力中起着关键作用。将环的大小从14成员类比物Tyr-C[D-Glu-Phe-gPhe-(L和D)-rLeu] 6a、6b减少一个原子到13成员类比物Tyr-C[D-Asp-Phe-gPhe-(L和D)-rLeu] 1、2，在μ和δ受体上的亲和力均下降，但在痛觉测定中效力提高，表明环的约束是类比物高疼痛效能的原因。至于Leu^5的D或L手性对受体选择性的影响，无论手性和环的大小，所有环状二叠体均表现出明显的μ选择性，并在δ受体上显示低效能。逆转对映异构体在μ受体上的活性与父类类似物相似或更强，但在δ受体上的活性低于父类类似物。