N-芴甲氧羰基-D-正缬氨酸 | 144701-24-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 缬氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-芴甲氧羰基-D-正缬氨酸
• 中文别名: 芴甲氧羰基-D-正缬氨酸；FMOC-D-正缬氨酸；Fmoc-D-正缬氨酸
• 英文名称: Fmoc-D-norvaline
• 英文别名: N-Fmoc-D-norvaline；Fmoc-D-Nva-OH；(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoic acid
• CAS: 144701-24-6
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: JBIJSEUVWWLFGV-GOSISDBHSA-N

物化性质

• 熔点：
  152-154°C
• 沸点：
  557.9±33.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-d-nva-oh
Synonyms:

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

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Section 3. Composition/information on ingredients.
Ingredient name: Fmoc-d-nva-oh
CAS number: 144701-24-6

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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.

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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.

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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.

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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, refrigerated.
Storage:

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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.

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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: C20H21NO4
Molecular weight: 339.4

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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.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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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.

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

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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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  N-芴甲氧羰基-D-正缬氨酸 在 哌啶 、 lithium aluminium tetrahydride 、 N-羟基-7-氮杂苯并三氮唑 、 PS-carbodiimide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.0h， 生成 (2R)-2-丙基哌嗪
  参考文献：
  名称：

  Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1H-benzimidazoles

  摘要：

  The vanilloid receptor-1 ( VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo-[ d] imidazoles as novel TRPV1 antagonists. Compound 46ad was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant ( CFA).

  DOI：

  10.1021/jm060065y
• 作为产物：
  描述：

  2-戊酮酸 在 甲酸 、 sodium carbonate 、 C₂₆H₃₄ClIrN₂O₂S 、 高碘酸 、 1,3-丙二胺 、 三乙胺 作用下， 以 甲醇 、 水 、 甲胺 为溶剂， 反应 18.0h， 生成 N-芴甲氧羰基-D-正缬氨酸
  参考文献：
  名称：

  使用铱基氢转移催化剂进行 α-酮酸的不对称还原胺化：获得未受保护的非天然 α-氨基酸

  摘要：

  描述了由带有手性N- (2-吡啶甲基)磺酰胺基配体的 Cp*Ir 配合物催化的 α-酮酸的直接不对称还原胺化。组合使用光学活性2-苯甘氨醇作为胺化剂对于使用甲酸的化学选择性和立体选择性转移氢化是有效的。随后用原高碘酸消除羟乙基部分可以以令人满意的分离产率（20个实例）提供各种未保护的α-氨基酸，并具有优异的光学纯度（高达> 99% ee）。

  DOI：

  10.1021/acs.orglett.3c04378

文献信息

• Determination of Chemical and Enantiomeric Purity of α‐Amino Acids and their Methyl Esters as N‐Fluorenylmethoxycarbonyl Derivatives Using Amylose‐derived Chiral Stationary Phases
  作者：Md. Fokhrul Islam、Suraj Adhikari、Man‐Jeong Paik、Wonjae Lee

  DOI：10.1002/bkcs.11694

  日期：2019.4

  were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L‐amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α‐amino acids and/or esters

  在衍生自直链淀粉衍生物的三个共价键合型手性固定相（CSP）上进行液相色谱对映体分离，同时测定α-氨基酸及其甲酯作为N-芴基甲氧基羰基（FMOC）衍生物的化学和对映体纯度。作为N-FMOC衍生物的α-氨基酸酯的对映体分离要好于相应的酸，尤其是对于CSP 1和2。对于一些市售消旋氨基酸甲酯中存在的化学杂质，如相应的消旋酸，观察到是0.49–17.50％。发现几种可商购的L-氨基酸甲酯的对映体杂质为0.03-0.58％，而相同分析物中存在的相应消旋酸的化学杂质为0.13-13.62％。
• Design, synthesis, and biological activity of new endomorphin analogs with multi-site modifications
  作者：Long Zhao、Keyao Luo、Zhaojuan Wang、Yuan Wang、Xianghui Zhang、Dongxu Yang、Mengtao Ma、Jingjing Zhou、Jiaming Cui、Jing Wang、Chao-zhen-yi Han、Xin Liu、Rui Wang

  DOI：10.1016/j.bmc.2020.115438

  日期：2020.5

  aimed to establish new EM analogs via introducing different bifunctional D-amino acids at position 2 of [(2-furyl)Map4]EMs. The combination of [(2-furyl)Map4]EMs with D-Arg2 or D-Cit2 yielded analogs with enhanced binding affinity to the μ-opioid receptor (MOR) and increased stability against enzymatic degradation (t1/2 >300 min). However, the agonistic activities of these analogs toward MOR were slightly

  内吗啡肽（EM）-1和EM-2是最有效的内源性镇痛药，可以有效地将镇痛与不良反应的风险区分开。外围给药后代谢稳定性差和止痛效果不佳，不利于将EMs用作新型临床止痛剂。因此，在这里，我们旨在通过在[（2-furyl）Map4] EMs的位置2引入不同的双功能D-氨基酸来建立新的EM类似物。[（2-furyl）Map4] EMs与D-Arg 2或D-Cit 2的组合产生类似物，与μ阿片受体（MOR）的结合亲和力增强，并且对酶促降解的稳定性提高（t 1/2> 300分钟）。但是，这些类似物对MOR的激动活性略有降低。与吗啡类似，类似物[D-Cit 2，（2-furyl）Map4] EM-1（10）的外周给药显着抑制小鼠在多种疼痛模型中的疼痛行为。此外，这种EM-1类似物具有降低的耐受性，对胃肠道活动性的影响较小，并且没有明显的运动障碍。与天然EM相比，本文合成的EM类似物具有增强的代谢稳定性，生物利用度和镇痛特性。
• Structure-guided engineering of<i>meso</i>-diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
  作者：Xinkuan Cheng、Xi Chen、Jinhui Feng、Qiaqing Wu、Dunming Zhu

  DOI：10.1039/c8cy01426d

  日期：——

  (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding D-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a

  内消旋-二氨基庚二酸酯脱氢酶（DAPDH）和突变酶是将2-酮酸转化为相应的D-氨基酸的生物催化剂的绝佳选择。然而，它们在庞大的2-酮酸如苯乙醛酸，2-氧代-4-苯基丁酸和吲哚-3-丙酮酸的对映选择性还原胺化中的应用仍然具有挑战性。在这项研究中，嗜热共生菌DAPDH（StDAPDH）的结构指导的位点饱和诱变产生了一个双位点突变体W121L / H227I，该突变体显示出对包括这些空间庞大底物在内的各种2-酮酸的酶活性有了显着提高。几D-氨基酸以光学纯的形式制备。底物分子对接至野生型和突变型W121L / H227I酶的活性位点中显示，突变型酶的底物结合腔已重塑以适应这些庞大的底物，从而导致更高的酶活性。这些结果为进一步整形底物结合袋和操纵底物与结合位点之间的相互作用以接近高活性的D-氨基酸脱氢酶以制备具有合成挑战性的D-氨基酸奠定了基础。
• Design and synthesis of 3,3′-biscoumarin-based c-Met inhibitors
  作者：Jimin Xu、Jing Ai、Sheng Liu、Xia Peng、Linqian Yu、Meiyu Geng、Fajun Nan

  DOI：10.1039/c4ob00364k

  日期：——

  A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3′-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met

  基于3,3'-biscoumarin hit 3的优化，合成了基于双香豆素的c-Met抑制剂库，该库从多种香豆素衍生物库中被鉴定为c-Met的非ATP竞争性抑制剂。在这些化合物中，38和40不仅显示出强大的酶活性，IC 50值分别为107 nM和30 nM，而且还抑制了BaF3 / TPR-Met和EBC-1细胞中的c-Met磷酸化。
• Parallel solid phase synthesis of tetrasubstituted diethylenetriamines via selective amide alkylation and exhaustive reduction of N-acylated dipeptides
  作者：Adel Nefzi、John M. Ostresh、Richard A. Houghten

  DOI：10.1016/s0040-4020(98)01043-6

  日期：1999.1

  Polyamines are a rapidly developing area of vital importance to biomedical science. Selective N-alkylation followed by N-terminal acylation and the complete reduction of carbonyl amide bonds enables the preparation by parallel solid phase synthesis of a wide range of N1,N5,1,4-tetrasubstituted-1,5-diamino-3-azapentane derivatives.

  多胺是对生物医学至关重要的快速发展领域。选择性的N-烷基化，接着通过N-末端酰化和的羰酰胺键的完全降低使得能够通过宽范围的N个并行固相合成制备1，N 5，1,4-四取代-1,5-二氨基-3- -氮杂戊烷衍生物。