苏型-(2RS)-4-苯基-3-乙酰氨基-2-羟基-4-氧代丁酸 | 42116-21-2

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苏型-(2RS)-4-苯基-3-乙酰氨基-2-羟基-4-氧代丁酸
• 中文别名: Z-试剂；S-(4,6-二甲基-2-嘧啶基)硫代羧酸苄酯；4,6-二甲基嘧啶-2-硫基甲酸苄酯；O-苄基S-(4,6-二甲基-2-嘧啶)羧硫代酯；4,6-二甲基嘧啶-2-硫代甲酸苄酯；O- 苄基 S-(4,6-二甲基-2-嘧啶)羧硫代酯
• 英文名称: 2-benzyloxycarbonylsulfanyl-4,6-dimethyl-pyrimidine
• 英文别名: benzyl S-(4,6-dimethylpyrimidin-2-yl) thiolcarbonate；benzyl S-4,6-dimethylpyrimidin-2-yl thiocarbonate；benzyl (4,6-dimethylpyrimidin-2-yl)sulfanylformate
• CAS: 42116-21-2
• 化学式: C₁₄H₁₄N₂O₂S
• mdl: MFCD00006082
• 分子量: 274.343
• InChiKey: DGAUFTRWMCEXLW-UHFFFAOYSA-N

物化性质

• 熔点：
  60-66 °C
• 沸点：
  455.2±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090
• 安全说明：
  S24/25
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存放于阴凉干燥处即可。

SDS

Name:	O-Benzyl S-(4 6-Dimethyl-2-Pyrimidinyl)Carbonothionate Material Safety Data Sheet
Synonym:	Carbonothioic Acid S-(4,6-Dimethyl-2-Pyrimidinyl) O-(Phenylmethyl)Ester
CAS:	42116-21-2

Section 1 - Chemical Product MSDS Name:O-Benzyl S-(4 6-Dimethyl-2-Pyrimidinyl)Carbonothionate Material Safety Data Sheet
Synonym:Carbonothioic Acid S-(4,6-Dimethyl-2-Pyrimidinyl) O-(Phenylmethyl)Ester

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
42116-21-2	O-Benzyl S-(4,6-Dimethyl-2-Pyrimidinyl	98.0	255-662-5

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May be harmful if inhaled.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a dry area. Keep refrigerated. (Store below 4C/39F.)

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 42116-21-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 64 - 66 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C14H14N2O2S
Molecular Weight: 274.34

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable.
Conditions to Avoid:
Incompatible materials, dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 42116-21-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
O-Benzyl S-(4,6-Dimethyl-2-Pyrimidinyl)Carbonothionate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 42116-21-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 42116-21-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 42116-21-2 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途：用于合成乌苯美司的中间体。

反应信息

• 作为反应物：
  描述：

  苏型-(2RS)-4-苯基-3-乙酰氨基-2-羟基-4-氧代丁酸 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 48.0h， 生成 Z-Sta-OMe
  参考文献：
  名称：

  在其N-末端结合亚砜等排体的含高抑素的肾素抑制剂的合成

  摘要：

  以天然他汀为原料合成了一种高抑素类似物 (2RS,4S,5S)N-isobutyl-5-amino-2-ethyl-4-hydroxy-7-methyloctanamide。(4S,5R)-3-benzyloxycarbonyl-5-formyl-4-isobutyl-2,2-二甲基恶唑烷的改良 Horner-Wadsworth-Emmons 反应是合成高抑素类似物的关键反应。N-末端前体的立体选择性和立体特异性合成，N-[(2R)-3-羟基-2-(1-萘基甲基)丙酰基]-L-正亮氨酸叔丁酯和高活性肾素抑制剂的全合成， (2RS,4S,5S)-N-isobutyl-5-[[N-[(2S)-2-(1-naphthylmethyl)-3-(2-pyrimidinylsulfonyl)propionyl]-L-norleucyl]amino]-2-描述了乙基-4-羟基-7-甲基辛酰胺。

  DOI：

  10.1246/bcsj.63.2224
• 作为试剂：
  描述：

  3-氨基-2-羟基-4-苯基丁酸 、 苏型-(2RS)-4-苯基-3-乙酰氨基-2-羟基-4-氧代丁酸 在 苏型-(2RS)-4-苯基-3-乙酰氨基-2-羟基-4-氧代丁酸 作用下， 以85.7的产率得到3-{[(苄氧基)羰基]氨基}-2-羟基-4-苯基丁酸
  参考文献：
  名称：

  Process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids,

  摘要：

  一种制备threo-3-氨基-2-羟基丁酰胺基乙酸的方法，包括以下步骤：将由通式表示的起始化合物反应：##STR1## 其中R.sub.1表示萘基或公式的基团：##STR2## 其中R.sub.6和R.sub.7分别表示氢、卤素、氨基或受保护的氨基、羟基或受保护的羟基、低级烷氧基或低级烷基，R.sub.2表示受保护的氨基，与由通式表示的起始化合物反应：##STR3## 其中R.sub.3表示氢或酯基残基，以获得threo-3-受保护氨基-2-羟基-4-酮丁酸或其由通式表示的酯：##STR4## 其中R.sub.1、R.sub.2和R.sub.3具有与上述相同的含义，然后将其还原为threo-3-受保护氨基-2-羟基丁酸或其由通式表示的酯：##STR5## 其中R.sub.1、R.sub.2和R.sub.3具有与上述相同的含义，进一步将上述化合物转化为由通式表示的3-氨基-2-羟基丁酸：##STR6## 其中R.sub.2'表示氨基或受保护的氨基，然后以传统方式缩合，与由通式表示的化合物：##STR7## 其中R.sub.4表示具有3-4个碳原子的烷基或3-鸟氨基丙基，在必要时先保护与反应无关的那些基团，然后去除功能基团的保护基团，以生成由通式表示的threo-3-氨基-2-羟基丁酰胺基乙酸：##STR8## 其中R.sub.1和R.sub.4具有与上述相同的含义。本发明还提供了由通式（III）表示的上述目标化合物的新中间体化合物和制备中间体化合物的方法。

  公开号：

  US04281180A1

文献信息

• Poststatin, a New Inhibitor of Prolyl Endopeptidase. VI. Endopeptidase Inhibitory Activity of Poststatin Analogues Containing Pyrrolidine Ring.
  作者：MAKOTO TSUDA、YASUHIKO MURAOKA、TETSUYA SOMENO、MACHIKO NAGAI、TAKAAKI AoYAGI、TOMIO TAKEUCHI

  DOI：10.7164/antibiotics.49.900

  日期：——

  Several pyrrolidine-containing analogues of poststatin were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Replacement of the postine residue with 2-oxo-2-(2-pyrrolidinyl)acetic acid increased the selectivity and inhibitory activity against prolyl endopeptidase. Benzyloxycarbonyl-L-phenylalanyl-(S)-2-oxo-2-(2-pyrrolidinyl)acetyl-D-phenylalanine was about 46 times as active to prolyl endopeptidase as natural poststatin.

  合成了几种含有吡咯烷结构片段的波斯他丁类似物，并研究了它们对脯氨酰内肽酶和组织蛋白酶B的体外抑制活性。将波斯他丁中的波斯汀残基替换为2-氧代-2-(2-吡咯烷基)乙酸，增加了其对脯氨酰内肽酶的选择性和抑制活性。苄氧羰基-L-苯丙氨酰-(S)-2-氧代-2-(2-吡咯烷基)乙酰基-D-苯丙氨酸对脯氨酰内肽酶的活性约为天然波斯他丁的46倍。
• Synthesis of 4-(methoxyethyl) monobactams by a chemicoenzymatic approach.
  作者：HARUO YAMASHITA、NOBUYOSHI MINAMI、KYOICHI SAKAKIBARA、SUSUMU KOBAYASHI、MASAJI OHNO

  DOI：10.1248/cpb.36.469

  日期：——

  As a key intermediate for the synthesis of monobactam analogues, cis-3-benzyloxycarbonyl-amino-4-(2-hydroxyehtyl)-2-azetidinone was synthesized from (4S)-4-methoxycarbonylmethyl-2-azetidinone, and converted into monobactams having a methoxyethyl group at the C-4 position of the β-lactam ring. Among the compounds synthesized, disodium (3S, 4R)-3[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoacetamido]-4-(2-methoxyethyl)-2-azetidinone-1-sulfonate showed strong activity against a variety of gram-negative bacteria except Pseudomonas aeruginosa. Furthemore, the 4-methoxyethyl derivatives exhibited excellent stabiliy to β-lactamases, and the syntheses of the corresponding trans isomer and 3α-methoxy derivatives are also described.

  作为合成单环β内酰胺类似物的关键中间体，顺-3-苄氧基羰基氨基-4-(2-羟乙基)-2-氮杂环丁酮是由(4S)-4-甲氧基羰基甲基-2-氮杂环丁酮合成的，并转化为在β-内酰胺环C-4位具有甲氧乙基基团的单环β内酰胺。在合成的化合物中，双钠盐(3S, 4R)-3[2-(2-氨基噻唑-4-基)-(Z)-2-羧基甲氧基亚胺乙酰氨基]-4-(2-甲氧乙基)-2-氮杂环丁酮-1-磺酸盐对多种革兰阴性细菌表现出强活性，除了铜绿假单胞菌。此外，4-甲氧乙基衍生物对β-内酰胺酶显示出优异的稳定性，并且相应的反式异构体和3α-甲氧基衍生物的合成也被描述。
• Oxidation of alkenes by a chiral non-porphyrinic oxidizing catalyst based on the bleomycin-Fe(II) complex
  作者：Akira Suga、Toru Sugiyama、Masami Otsuka、Masaji Ohno、Yukio Sugiura、Kenji Maeda

  DOI：10.1016/s0040-4020(01)86376-6

  日期：——

  A synthetic model for the metal binding site of bleomycin with 4-dimethylaminopyridine nucleos namely PYML-8, shows dioxygen activation up to 125% of that of bleomycin of PYML-8 to give a set of products including optically active epoxide. The product composition is dependent on iron, oxygen source, and reducing agent employed, suggesting varied active species generated from each complex system.

  博来霉素具有4-二甲基氨基吡啶核苷的PYML-8的金属结合位点的合成模型显示，双氧活化高达PYML-8博来霉素的125％，从而得到一组包括旋光性环氧化物的产物。产品组成取决于所使用的铁，氧源和还原剂，表明从每个复杂系统中生成的活性物质各不相同。
• Semisynthesis of 14C-labelled leupeptin.
  作者：TETSUSHI SAINO、TETSUYA SOMENO、HIROSHI MIYAZAKI、SHINICHI ISHII

  DOI：10.1248/cpb.30.2319

  日期：——

  ^<14>C-Labelled leupeptin, Ac-L-[U-14C]-leucyl-L-leucyl-L-argininal, with a specific radioactivity of 20.9 mCi/mmol was prepared by a semisynthetic procedure in which L-leucyl-L-argininal dibutylacetal obtained by an enzymatic cleavage of leupeptin dibutyl-acetal with thermolysin was employed as a key compound. The chemical and radiochemical purities of the labelled leupeptin were found to be over 99% by high performance liquid chromatography using radioisotope and ultraviolet detectors.

  采用半合成方法制备了^<14>C 标记的亮肽，Ac-L-[U-14C]-亮氨酰-L-亮氨酰-L-精氨醛，比放射性为 20.9 mCi/mmol。通过使用放射性同位素和紫外线检测器的高效液相色谱法，发现标记的亮肽的化学纯度和放射化学纯度均超过 99%。
• Stereospecific Synthesis of a Novel Farnesyl Protein Transferase Inhibitor Valinoctin A and Its Analogues.
  作者：MAKOTO TSUDA、YASUHIKO MURAOKA、TOMIO TAKEUCHI、RYUICHI SEKIZAWA、KAZUO UMEZAWA

  DOI：10.7164/antibiotics.49.1031

  日期：——

  (2S, 3R)-3-Amino-2-hydroxyoctanoic acid was synthesized by Curtius rearrangement of an azide derivative of (S)-malic acid. Total syntheses of valinoctin A and its analogues were achieved by a coupling of (2S, 3R)-3-amino-2-hydroxyoctanoic acid moiety with L-valine or several other amino acids moieties. 2S configuration of 3-amino-2-hydroxyoctanoic acid moiety was found to be important for the inhibitory activity and the L-valine moiety of valinoctin A was exchangeable with other L-amino acids.

  (2S，3R)-3-氨基-2-羟基辛酸是通过(S)-苹果酸的叠氮衍生物的 Curtius 重排合成的。通过（2S，3R）-3-氨基-2-羟基辛酸与 L-缬氨酸或其他几种氨基酸的偶联，实现了缬氨辛 A 及其类似物的全合成。研究发现，3-氨基-2-羟基辛酸的 2S 构型对抑制活性很重要，而缬氨辛 A 的 L-缬氨酸可与其他 L-氨基酸交换。

表征谱图