3-甲基-2-氧基戊酸 | 1460-34-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 3-甲基-2-氧基戊酸
• 中文别名: dl-3-甲基-2-氧代缬草酸；3-甲基-2-氧代戊酸；α-酮-β-甲基缬草酸；DL-3-甲基-2-氧戊酸
• 英文名称: 2-oxo-3(RS)-methylvaleric acid
• 英文别名: 3-methyl-2-oxopentanoic acid；3-methyl-2-oxovaleric acid
• CAS: 1460-34-0
• 化学式: C₆H₁₀O₃
• mdl: MFCD00002582
• 分子量: 130.144
• InChiKey: JVQYSWDUAOAHFM-UHFFFAOYSA-N

物化性质

• 熔点：
  42°C
• 沸点：
  84 °C / 18mmHg
• 密度：
  1.087±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：130 mg/mL（998.92 mM）
• LogP：
  0.17
• 物理描述：
  Solid
• 碰撞截面：
  127.1 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]
• 稳定性/保质期：
  如果按照规定使用和储存，则不会发生分解，目前没有已知的危险反应。应避免接触氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 毒性总结

3-甲基-2-氧代戊酸是由异亮氨酸通过细胞质支链氨基转移酶1产生的，之后它被支链酮酸脱氢酶E1进一步降解为2-甲基-1-羟基丁基-硫辛酸磷酸。它被用作枫糖尿症（MSUD）的临床标志。枫糖尿症是由支链酮酸脱氢酶复合物的缺乏引起的，导致血液、尿液和脑脊液中支链氨基酸及其相应的酮酸和羟基酸的积累，从而引起神经损伤和精神发育迟滞。

3-Methyl-2-oxovaleric acid is produced from isoleucine by cytosolic branched chain aminotransferase 1, whereupon it is further degraded by branched chain keto acid dehydrogenase E1 to 2-methyl-1-hydroxybutyl-ThPP. It is used as a clinical marker for maple syrup urine disease (MSUD). MSUD is caused by a deficiency of the branched-chain -keto acid dehydrogenase complex resulting in an accumulation of branched-chain amino acids and the corresponding -keto-and -hydroxy acids in blood, urine and cerebrospinal fluid causing neurological damage and mental retardation.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

长期高水平的3-甲基-2-戊酸与枫糖尿症有关。

Chronically high levels of 3-methyl-2-oxovaleric acid are associated with Maple Syrup Urine Disease.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S36/37/39
• 危险类别码：
  R36/37/38
• 储存条件：
  请将贮藏器密封保存，并存放在阴凉、干燥的地方。同时，确保工作环境有良好的通风或排气设施。

SDS

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Section I.Chemical Product and Company Identification
Chemical Name 3-Methyl-2-oxovaleric Acid
Portland OR
Synonym
2-Keto-3-methyl-n-pentanoic Acid
Chemical Formula
CH 3 CH 2 CH(CH 3 )COCOOH
CAS Number
1460-34-0
(International)

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Section II. Composition and Information on Ingredients
Chemical Name CAS Number Percent (%) TLV/PEL Toxicology Data
3-Methyl-2-oxovaleric Acid Min. 90.0 Not available. Not available.
1460-34-0
(Tit.)

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Section III. Hazards Identification
Acute Health Effects
Irritating to eyes and skin on contact. Inhalation causes irritation of the lungs and respiratory system . Inflam m ation of
the eye is characterized by redness, w atering, and itching. Skin inflam m ation is characterized by itching, scaling,
reddening, or, occasionally, blistering.
Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound.
Chronic Health Effects CARCINOGENIC EFFECTS : Not available.
MUTAGENIC EFFECTS : Not available.
TERATOGENIC EFFECTS : Not available.
DEVELOPMENTAL TOXICITY : Not available.
Repeated or prolonged exposure to this compound is not known to aggravate existing medical conditions.

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Section IV. First Aid Measures
Eye Contact
C heck for and rem ove any contact lenses. In case of contact, im m ediately flush eyes w ith plenty of w ater for at least 15
minutes. Get medical attention.
Skin Contact
In case of contact, im m ediately flush skin w ith plenty of w ater. Rem ove contam inated clothing and shoes. W ash
clothing before reuse. Thoroughly clean shoes before reuse. Get medical attention.
Inhalation
If the victim is not breathing, perform m outh-to-m outh resuscitation. Loosen tight clothing such as a collar, tie, belt or
w aistband. If breathing is difficult, oxygen can be adm inistered. Seek m edical attention if respiration problem s do not
improve.
Ingestion
IN D U C E V O M ITIN G by sticking finger in throat. Low er the head so that the vom it w ill not reenter the m outh and throat.
Loosen tight clothing such as a collar, tie, belt or w aistband. If the victim is not breathing, perform m outh-to-m outh
resuscitation. Exam ine the lips and m outh to ascertain w hether the tissues are dam aged, a possible in dication that the
toxic material was ingested; the absence of such signs, however, is not conclusive.

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Section V. Fire and Explosion Data
Auto-Ignition
Flammability Not available.
May be combustible at high temperature.
Flash Points Flammable Limits
Not available.
Not available.
Combustion Products
These products are toxic carbon oxides (CO, CO 2 ).
Fire Hazards
Not available.
Explosion Hazards
Risks of explosion of the product in presence of mechanical impact: Not available.
Risks of explosion of the product in presence of static discharge: Not available.
Fire Fighting Media
SMALL FIRE: Use DRY chemical powder.
and Instructions LARGE FIRE: Use water spray, fog or foam. DO NOT use water jet.
Consult with local fire authorities before attempting large scale fire-fighting operations.
Continued on Next Page
3-Methyl-2-oxovaleric Acid

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Section VI. Accidental Release Measures
Spill Cleanup
Irritating material.
Instructions U se a shovel to put the m aterial into a convenient w aste disposal container. Finish cleaning the spill by rinsing any
contam inated surfaces w ith copious am ounts of w ater. C onsult federal, state, and/or local authorities for assistance on
disposal.

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Section VII. Handling and Storage
Handling and Storage
IRRITA N T. REFRIG ERA TE. K eep aw ay from heat. M ech anical exhaust required. W hen not in use, tightly seal the
container and store in a dry, cool place. Avoid excessive heat and light. Do not breathe dust.
Information
Always store away from incompatible compounds such as oxidizing agents.

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Section VIII. Exposure Controls/Personal Protection
Engineering Controls
U se process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recom m ended exposure lim its. If user operations generate dust, fum e or m ist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection
Splash goggles. Lab coat. D ust respirator. Boots. G loves. Suggested protective clothing m ight not be sufficient;
consult a specialist BEFORE handling this product. Be sure to use a MSHA/NIOSH approved respirator or equivalent.
Exposure Limits
Not available.

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Section IX. Physical and Chemical Properties
Physical state @ 20°C Solubility
Solid. (White Lumps.)
Not available.
Specific Gravity Not available.
Molecular Weight Partition Coefficient
130.14
Not available.
Boiling Point Vapor Pressure
84°C (183.2°F) @ 18 mmHg Not applicable.
Melting Point Vapor Density
42°C (107.6°F) Not available.
Refractive Index Volatility
Not available. Not available.
Critical Temperature Odor
Not available. Not available.
Viscosity Taste
Not available. Not available.

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Section X. Stability and Reactivity Data
Stability

---

This material is stable if stored under proper conditions. (See Section VII for instructions)
Conditions of Instability
Avoid excessive heat and light.
Incompatibilities
Reactive with oxidizing agents.

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Section XI. Toxicological Information
RTECS Number
Not available.
Routes of Exposure
Eye Contact. Ingestion. Inhalation.
Toxicity Data
Not available.
Chronic Toxic Effects CARCINOGENIC EFFECTS : Not available.
MUTAGENIC EFFECTS : Not available.
TERATOGENIC EFFECTS : Not available.
DEVELOPMENTAL TOXICITY : Not available.
Repeated or prolonged exposure to this compound is not known to aggravate existing medical conditions.
Acute Toxic Effects
Irritating to eyes and skin on contact. Inhalation causes irritation of the lungs and respiratory system . Inflam m ation of
the eye is characterized by redness, w atering, and itching. Skin inflam m ation is characterized by itching, scaling,
reddening, or, occasionally, blistering.
Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound.
Continued on Next Page
3-Methyl-2-oxovaleric Acid

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Section XII. Ecological Information
Ecotoxicity
Not available.
Environmental Fate
Not available.

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Section XIII. Disposal Considerations
Waste Disposal Recycle to process, if possible. C onsult your local regional authorities. You m ay be able to dissolve or m ix m aterial w ith
a com bustible solvent and burn in a chem ical incinerator equipped w ith an afterburner and scrubber system . O bserve all
federal, state and local regulations when disposing of the substance.

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Section XIV. Transport Information
DOT Classification
Not a DOT controlled material (United States).
PIN Number
Not applicable.
Proper Shipping Name
Not applicable.
Packing Group (PG)
Not applicable.
DOT Pictograms

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Section XV. Other Regulatory Information and Pictograms
TSCA Chemical Inventory
T h is p r o d u c t is NOT o n t h e E P A T o x ic S u b s t a n c e s C o n t r o l A c t (T S C A ) in v e n t o r y . T h e f o llo w in g n o t ic e s a r e r e q u ir e d b y 4 0
(EPA) CFR 720.36 (C) for those products not on the inventory list:
(i) These products are supplied solely for use in research and developm ent by or under the supervision of a technically
qualified individual as defined in 40 CFR 720.0 et sec.
(ii) The health risks of these products have not been fully determ ined. A ny inform ation that is or becom es available w ill
be supplied on an MSDS sheet.
WHMIS Classification
Not available. Not available.
(Canada)
EINECS Number (EEC)
215-955-0
EEC Risk Statements
R36/37/38- Irritating to eyes, respiratory system and skin.
Japanese Regulatory Data
ENCS No. (2)-1503

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Section XVI.
Version 1.0
Validated on 3/1/2007.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

毒性

该物质被列为GRAS（FEMA）。

使用限量

• 无醇饮料、冷饮、水果冰品、汤品、甜沙司：1.0～10.0 mg/kg
• 含醇饮料、干酪、凝胶制品、布丁、代乳品、乳制品、代糖品：0.5～5.0 mg/kg
• 胶姆糖、糖果、糖霜、调味汁、果酱、果冻、复水蔬菜：1.0～5.0 mg/kg
• 调味品：0.5～10 mg/kg
• 油脂：0.3～10 mg/kg
• 速溶咖啡和茶、加工蔬菜、加工水果：0.1～1.0 mg/kg
• 软糖：0.1～5.0 mg/kg
• 调味香料：50～100 mg/kg

生物活性

3-甲基-2-氧化戊酸是一种神经毒素，也是一种酸性原和代谢毒素。它是由支链氨基酸不完全分解产生的异常代谢物。

靶点

Human 内源性代谢物

反应信息

• 作为反应物：
  描述：

  3-甲基-2-氧基戊酸 在 ammonium hydroxide 、 葡萄糖 、 glucose dehydrogenase from Bacillus megaterium 、 Acinetobacter tandoii glutamate dehydrogenase 、 还原型辅酶Ⅰ 作用下， 以 aq. buffer 为溶剂， 生成 isoleucine
  参考文献：
  名称：

  谭氏不动杆菌谷氨酸脱氢酶通过生物催化级联反应不对称合成L-高丙氨酸的合理工程

  摘要：

  L-高丙氨酸是合成几种手性药物的有用组成部分，通常是通过使用天然氨基酸作为廉价起始反应物的生物级联反应合成的。然而，添加昂贵的外部辅因子和亮氨酸脱氢酶对中间体2-酮丁酸的低效率是工业应用中的两个主要挑战。本文中，鉴定了来自不动杆菌的双辅因子依赖性谷氨酸脱氢酶（At GluDH），当使用全细胞催化时，有助于充分利用辅因子的细胞内池。通过重建酶和底物2-酮丁酸的末端甲基之间的疏水网络，At的严格底物特异性成功地改变了针对α-酮戊二酸的GluDH，最有效的突变体（K76L / T180C）获得的活性是野生型蛋白的17.2倍。为了帮助释放传质限制，成功构建了三酶共表达系统。使用1M大号-苏氨酸，这是接近的溶解度极限，我们得到的产率99.9％大号-homoalanine在仅3.5小时不添加外部辅酶至级联，得到99.9％ee的和29.2克L- -1 ħ - 1时空产量。此外，的活动设计在朝向其他疏水性氨基酸的GluDH也提高了1

  DOI：

  10.1039/d1cy00376c
• 作为产物：
  描述：

  isoleucine 在 ω-transaminase 作用下， 生成 3-甲基-2-氧基戊酸
  参考文献：
  名称：

  通过伯胺的氨基级联转移到酮酸上的非天然氨基酸的生物催化不对称合成。

  摘要：

  逃往山上：通过α-转氨酶反应作为平衡转移剂，成功克服了α-转氨酶催化的氨基酸和酮酸之间的氨基转移平衡失衡，从而有效地不对称合成了多种非天然氨基酸包括大号-叔-亮氨酸和d -苯基甘氨酸。

  DOI：

  10.1002/cctc.201300571

文献信息

• Total Synthesis of TMC-95A and -B via a New Reaction Leading to <i>Z</i>-Enamides. Some Preliminary Findings as to SAR
  作者：Songnian Lin、Zhi-Qiang Yang、Benjamin H. B. Kwok、Michael Koldobskiy、Craig M. Crews、Samuel J. Danishefsky

  DOI：10.1021/ja049821k

  日期：2004.5.1

  A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues

  提供了蛋白酶体抑制剂 TMC-95A 和 -B 的全合成的完整说明。合成的一个关键特征涉及通过α-甲硅烷基烯丙基酰胺的热重排安装顺式丙烯酰胺部分。讨论了烯酰胺形成反应的范围和机理。还提供了一些 SAR 研究的初步结果。发现简化的类似物可以保留蛋白酶体抑制的全部效力。
• Expanding ester biosynthesis in Escherichia coli
  作者：Gabriel M Rodriguez、Yohei Tashiro、Shota Atsumi

  DOI：10.1038/nchembio.1476

  日期：2014.4

  The use of CoA thioester intermediates drives formation of small- and medium-sized esters in metabolically engineered E. coli cells, including doubly branched chains generated with enzymes from amino acid degradation pathways. To expand the capabilities of whole-cell biocatalysis, we have engineered Escherichia coli to produce various esters. The alcohol O-acyltransferase (ATF) class of enzyme uses acyl-CoA units for ester formation. The release of free CoA upon esterification with an alcohol provides the free energy to facilitate ester formation. The diversity of CoA molecules found in nature in combination with various alcohol biosynthetic pathways allows for the biosynthesis of a multitude of esters. Small to medium volatile esters have extensive applications in the flavor, fragrance, cosmetic, solvent, paint and coating industries. The present work enables the production of these compounds by designing several ester pathways in E. coli. The engineered pathways generated acetate esters of ethyl, propyl, isobutyl, 2-methyl-1-butyl, 3-methyl-1-butyl and 2-phenylethyl alcohols. In particular, we achieved high-level production of isobutyl acetate from glucose (17.2 g l−1). This strategy was expanded to realize pathways for tetradecyl acetate and several isobutyrate esters.

  利用辅酶A硫酯中间体驱动代谢工程改造的大肠杆菌细胞中形成小分子和中分子酯类,包括通过氨基酸降解途径的酶生成双支链酯。为了扩展全细胞生物催化能力,我们改造了大肠杆菌生产多种酯类。醇O-酰基转移酶类使用酰基-辅酶A单元进行酯形成。与醇酯化释放出自由辅酶A提供自由能促进酯形成。自然界中发现的各种辅酶A分子与多种醇生物合成途径结合,允许生物合成大量酯。小到中挥发性酯在风味、香料、化妆品、溶剂、涂料和涂层行业有广泛应用。本工作通过在大肠杆菌中设计多种酯途径实现这些化合物的生产。改造的途径生成了乙酸酯的乙基、丙基、异丁基、2-甲基-1-丁基、3-甲基-1-丁基和2-苯乙基醇。特别是,我们实现了从葡萄糖(17.2 g l-1)高产率生产乙酸异丁酯。这一策略扩展到实现几种异丁酸酯和乙酸十四烷酯的途径。
• Synthesis of di- and tripeptide analogues containing α-ketoamide as a new core structure for inhibition of HIV-1 protease
  作者：Mahmoud M Sheha、Nadia M Mahfouz、Hoda Y Hassan、Adel F Youssef、Tsutomu Mimoto、Yoshiaki Kiso

  DOI：10.1016/s0223-5234(00)00187-2

  日期：2000.10

  quantitative yields. The alpha-keto tripeptides (18-21) were obtained by oxidation of the hydroxyl group of Apns (PI) in the appropriate tripeptide, iQOA-Val-Apns-(un)substituted Thz(Oxa)-NHBu(t) with DMSO/DCC. Preliminary evaluation of the activity of the synthesized derivatives was determined as percentage of enzyme inhibition at 5 microM and 50 nM levels of the di- and tripeptides respectively. The alpha-ketoamides

  设计和合成了含有α-酮酰胺作为新的核心结构并掺入别苯基去甲他汀（Apns）作为过渡态模拟物的二肽和三肽类似物，希望获得一种新型的HIV-1蛋白酶抑制剂。直接前体Apns-Thz-NHBu（t）是通过Boc-Apns与N-叔丁基丁基Thz-4-羧酰胺盐酸盐偶联制得的。除去Boc基团，然后与各自的α-酮酸残基（P2）偶联，以几乎定量的产率得到所需的二肽（8-12）。通过用适当的三肽iQOA-Val-Apns-（未）取代的Thz（Oxa）-NHBu（t）中的Apns（PI）氧化Apns（PI）的羟基获得α-酮基三肽（18-21） DCC。对合成衍生物活性的初步评估被确定为分别在二肽和三肽的5 microM和50 nM水平下酶抑制的百分比。相对于作为HIV-1蛋白酶抑制剂的母体同等异构体，α-酮酰胺显示出显着增强的效力，并且被证明是酶抑制剂开发的有希望的新核心结构。尝试使用LFE模型的定量方法，将
• Chemiluminescent products of reaction between .ALPHA.-keto acids and 4,5-diaminophthalhydrazide.
  作者：Hiromi ARAKAWA、Junichi ISHIDA、Masatoshi YAMAGUCHI、Masaru NAKAMURA

  DOI：10.1248/cpb.38.3491

  日期：——

  The chemiluminescent products formed from α-keto acids and 4, 5-diaminophthalhydrazide dihydrochloride were characterized as corresponding 3-substituted-7, 8-dihydropyridazino[4, 5-g]quinoxaline-2, 6, 9(1H)-trione. The chemiluminescence properties of the products are described.

  α-酮酸与4,5-二氨基邻苯二甲酰肼二盐酸盐反应形成的化学发光产物被表征为相应的3-取代-7,8-二氢吡啶并[4,5-g]喹唑啉-2,6,9(1H)-三酮。该产物的化学发光性质进行了描述。
• [EN] SYNTHESIS METHOD AND INTERMEDIATES USEFUL IN THE PREPARATION OF PYRROLOBENZODIAZEPINES<br/>[FR] PROCÉDÉ DE SYNTHÈSE ET INTERMÉDIAIRES POUVANT SERVIR À PRÉPARER DES PYRROLOBENZODIAZÉPINES
  申请人：SPIROGEN SARL

  公开号：WO2013053872A1

  公开（公告）日：2013-04-18

  A compound of formula I wherein: R7 is selected from: ORA, where RA is selected from C1-4 saturated alkyl, optionally substituted by phenyl, which may bear a chloro substituent, pyridyl and furanyl; chloro; NH2; -CH2-O-C(=O)Me; R8 is OProt°, where Prot° is a silicon-based oxygen protecting group orthogonal to Rc; R9 is selected from H, methyl and methoxy; Rs is selected from CF3, (CF2)3CF3, CH3 and (formula 2) and Rc is selected from: (i) -C(=O)-ORC1, where RC1 is a saturated C1-4 alkyl group; (ii) -CH2-O-C(=0)RC2, where RC2 is methyl or phenyl; (iii) -CH2-O-Si-(RSi1)(RSi2)(RSi3), where RSi1, RSi2, RSi3 are independently selected from C1-6 a saturated alkyl group and a phenyl group; and (iv) -C(-YRC3)(-YRC4) where each Y is independently O or S, and where RC3 and RC4 are independently a saturated C1-4 alkyl group, or together form a C2-3 alkylene.

  式I的化合物，其中：R7选自：ORA，其中RA选自C1-4饱和烷基，可选择地被苯基取代，该苯基可能带有氯取代基，吡啶基和呋喃基；氯；NH2；-CH2-O-C(=O)Me；R8为OProt°，其中Prot°是与Rc正交的基于硅的氧保护基团；R9选自H，甲基和甲氧基；Rs选自CF3，(CF2)3CF3，CH3和（式2）；Rc选自：(i)-C(=O)-ORC1，其中RC1是饱和的C1-4烷基基团；(ii)-CH2-O-C(=0)RC2，其中RC2是甲基或苯基；(iii)-CH2-O-Si-(RSi1)(RSi2)(RSi3)，其中RSi1，RSi2，RSi3分别选自C1-6饱和烷基和苯基；以及(iv)-C(-YRC3)(-YRC4)，其中每个Y独立地为O或S，且RC3和RC4独立地为饱和的C1-4烷基基团，或者一起形成C2-3亚烷基。