calcium (R)-pantothenate | 137-08-6

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 维生素B类药
• 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
• 英文名称: calcium (R)-pantothenate
• 英文别名: Calcium pantothenate；calcium D-pantothenate；D-pantothenic acid hemicalcium salt；D(+)pantothenic acid calcium salt；pantothenic acid calcium salt；calcium 3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoate；Pantothenic acid, calcium salt, D-；calcium;3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoate
• CAS: 137-08-6
• 化学式: 2C₉H₁₆NO₅*Ca
• 分子量: 476.537
• InChiKey: SXRRAEDIIGNDNU-FJXQXJEOSA-M

物化性质

• 熔点：
  190 °C
• 比旋光度：
  26.5 º (c=5, in water)
• 闪点：
  145 °C
• 溶解度：
  H2O: 50 mg/mL at 25 °C, 澄清, 近乎无色
• LogP：
  -0.849 (est)
• 稳定性/保质期：

  D-泛酸钙具有维生素的生理活性，而L-泛酸钙没有。D-泛酸钙参与体内蛋白质、脂肪和糖的新陈代谢。

计算性质

• 辛醇/水分配系数(LogP)：
  -2.76
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S24/25
• 危险类别码：
  R20/21/22,R48,R41,R37/38
• WGK Germany：
  1
• 海关编码：
  2936240000
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  RU4375000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  请将产品储存于阴凉干燥处。

SDS

Name:	D-(+)-Pantothenic Acid Calcium Salt Material Safety Data Sheet
Synonym:	Dextrocalcium Pantothenate; Pantothenate Calciu
CAS:	137-08-6

Section 1 - Chemical Product MSDS Name:D-(+)-Pantothenic Acid Calcium Salt Material Safety Data Sheet
Synonym:Dextrocalcium Pantothenate; Pantothenate Calciu

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
137-08-6	DIHYDROXYDIMETHYLOXOBU	100.0	205-278-9

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

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Light sensitive.Air sensitive.Moisture sensitive.
Potential Health Effects
Eye:
Contact may cause transient eye irritation.
Skin:
May cause skin irritation. Low hazard for usual industrial handling.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. Low hazard for usual industrial handling.
Inhalation:
May cause respiratory tract irritation. Low hazard for usual industrial handling.
Chronic:
No information found.

---

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:
Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Get medical aid if irritation develops or persists. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. Get medical aid if irritation or symptoms occur.
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 if cough or other symptoms appear.
Notes to Physician:

---

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. Dusts at sufficient concentrations can form explosive mixtures with air. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Vapors may be heavier than air. They can spread along the ground and collect in low or confined areas.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Do NOT get water inside containers. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up or absorb material, then place into a suitable clean, dry, closed container for disposal. Avoid generating dusty conditions. Provide ventilation. Do not get water inside containers.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Wash hands before eating. Remove contaminated clothing and wash before reuse. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Avoid contact with air and sunlight. Keep from contact with moist air and steam.
Storage:
Do not store in direct sunlight. Keep refrigerated. (Store below 4C/39F.) Keep container closed when not in use. Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Store protected from moisture. Store protected from light and air.

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 137-08-6: 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.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: none reported
pH: 7.2-8.0, 5% solution
Vapor Pressure: Negligible.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 195 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: Soluble in water.
Specific Gravity/Density: Not available.
Molecular Formula: (C9H16NO5)2Ca
Molecular Weight: 476.3114

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
High temperatures, incompatible materials, light, dust generation, exposure to air, excess heat, exposure to moist air or water.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 137-08-6: RU4375000 LD50/LC50:
CAS# 137-08-6: Oral, mouse: LD50 = 10 gm/kg; Oral, rat: LD50 = >10 gm/kg.
Carcinogenicity:
DIHYDROXYDIMETHYLOXOBU - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

---

Section 12 - ECOLOGICAL INFORMATION

---

Section 13 - DISPOSAL CONSIDERATIONS
Products which are considered hazardous for supply are classified as Special Waste and the disposal of such chemicals is covered by regulations which may vary according to location. Contact a specialist disposal company or the local waste regulator for advice. Empty containers must be decontaminated before returning for recycling.

---

Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 137-08-6: 0
Canada
CAS# 137-08-6 is listed on Canada's DSL List.
CAS# 137-08-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 137-08-6 is listed on the TSCA inventory.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

根据提供的信息，消旋泛酸钙的生产方法可以总结如下：

1. 首先制备2,2-二甲基-3-羟基丙醛。具体操作为：在14-20℃下将甲醛与无水碳酸钾混合，然后滴加异丁醛，在14-20℃下保温搅拌反应3小时后静置0.5小时。

2. 然后制备γ-丁内酯。具体操作为：将2,2-二甲基-3-羟基丙醛溶解于水中，加入氰化钠和氯化钙溶液，在60-65℃下与硫酸反应6小时，再升温至80-85℃反应3小时，减压浓缩，加入乙醇沉淀无机盐。

3. 接着制备泛酸钙。具体操作为：将β-氨基丙酸、甲醇和石灰加热水解后与γ-丁内酯反应，在室温下放置40小时后分离结晶并过滤，得到消旋泛酸钙。

4. 最后拆分消旋泛酸钙以获得左旋和右旋泛酸钙。具体操作为：将2/3量的消旋泛酸钙与少量左旋泛酸钙晶种加热水解后育晶2小时（当比旋光度达+6°-+8°时），分离结晶并洗涤，得到左旋泛酸钙；然后将其余1/3的消旋泛酸钙搅拌溶解在35-40℃的滤液中，在15℃下加入少量右旋泛酸钙晶种育晶2小时（当比旋光度达-0.6°- -0.8°时），分离结晶并洗涤，真空干燥得到右旋泛酸钙。

请注意，以上生产方法可能需要在专业人员指导下进行，并确保遵守所有相关的安全和环境法规。

反应信息

• 作为反应物：
  描述：

  calcium (R)-pantothenate 在 D(+)-10-樟脑磺酸 、 三氟乙酸 作用下， 生成 D-泛酸
  参考文献：
  名称：

  比例荧光探针成像活细胞中的泛肽酶

  摘要：

  泛酸酶催化泛酸裂解为泛酸（维生素B5）和半胱胺，参与氧化应激的调节，泛酸的循环利用和细胞迁移。然而，由于缺乏合适的荧光成像探针，进一步阐明该酶的细胞功能受到很大限制。通过将泛酸与甲酚紫结合，在此我们开发了一种新的荧光探针CV-PA用于泛酶的测定。该探头不仅具有较长的分析波长，而且还显示线性比例（I 628/582 nm）对泛酶的荧光反应，范围为5–400 ng / mL，检出限为4.7 ng / mL。该探针已用于评估不同抑制剂的效率并定量检测血清样品中的泛酸酶，表明胎牛血清和新生小牛血清中的泛酸酶比正常人血清中的泛酸酶高得多。值得注意的是，使用该探针首次实现了在不同活细胞（LO2和HK-2）中泛酶的比例成像和原位定量比较。已经发现，LO2细胞中泛酶的水平比HK-2细胞中泛酶的水平大得多，如通过蛋白质印迹分析进一步证实的。提出的探针可能有助于更好地了解泛素酶在与泛素相关的病理生理过程中的特定功能。

  DOI：

  10.1021/acs.analchem.7b03303
• 作为产物：
  描述：

  calcium pantothenate 以 甲醇 、 水 为溶剂， 生成 calcium (R)-pantothenate 、 calcium (S)-pantothenate
  参考文献：
  名称：

  泛酸钙。第3部分。（1）通过选择性结晶和外消旋作用制备相同生物活性对映体的方法

  摘要：

  通过单个对映异构体的直接分级结晶，从外消旋化合物获得了光学纯的泛酸钙（R）。已经开发出了一种有效的消旋形式，即生物活性的泛酸钙（S）不会分解为泛内酯，从而产生了一种简单，完整而有效的技术。实验室中详细阐述的结果随后已成功地应用于工业规模的过程中。

  DOI：

  10.1021/op800189g
• 作为试剂：
  描述：

  α-乙酰基-γ-丁内酯 在 烟酸 、 硫酸氢铵 、 potassium dihydrogenphosphate 、 2-甲基-3-羟基-4,5-二羟甲基吡啶 、 葡萄糖 、 Inositol 、 维生素B1 、 硼酸 、 calcium (R)-pantothenate 、 magnesium sulfate 、 copper(II) sulfate 、 zinc(II) sulfate 、 potassium iodide 、 calcium chloride 、 manganese(ll) chloride 、 iron(II) chloride 、 D-生物素 作用下， 以 乙醇 、 水 为溶剂， 反应 96.0h， 以19%的产率得到(3R)-3-[(1S)-1-hydroxyethyl]oxolan-2-one
  参考文献：
  名称：

  Synthesis of homochiral syn- andanti-α-(hydroxyethyl)-γ-butyrolactones via microbial reduction

  摘要：

  Various yeast and mould strains were tested in the reduction of alpha-acetyl-gamma-butyrolactone. syn-(3R,1'R)-alpha-(Hydroxyethyl)-gamma-butyrolactone 2 and anti-(3R,1'S) isomer 3 were obtained enantiomerically pure. Good enantiomeric excesses are described for the corresponding enantiomers.

  DOI：

  10.1016/0957-4166(94)80067-7

文献信息

• Acyl-group specificity of AHL synthases involved in quorum-sensing in <i>Roseobacter</i> group bacteria
  作者：Lisa Ziesche、Jan Rinkel、Jeroen S Dickschat、Stefan Schulz

  DOI：10.3762/bjoc.14.112

  日期：——

  N-Acylhomoserine lactones (AHLs) are important bacterial messengers, mediating different bacterial traits by quorum sensing in a cell-density dependent manner. AHLs are also produced by many bacteria of the marine Roseobacter group, which constitutes a large group within the marine microbiome. Often, specific mixtures of AHLs differing in chain length and oxidation status are produced by bacteria, but how the biosynthetic enzymes, LuxI homologs, are selecting the correct acyl precursors is largely unknown. We have analyzed the AHL production in Dinoroseobacter shibae and three Phaeobacter inhibens strains, revealing strain-specific mixtures. Although large differences were present between the species, the fatty acid profiles, the pool for the acyl precursors for AHL biosynthesis, were very similar. To test the acyl-chain selectivity, the three enzymes LuxI₁ and LuxI₂ from D. shibae DFL-12 as well as PgaI₂ from P. inhibens DSM 17395 were heterologously expressed in E. coli and the enzymes isolated for in vitro incubation experiments. The enzymes readily accepted shortened acyl coenzyme A analogs, N-pantothenoylcysteamine thioesters of fatty acids (PCEs). Fifteen PCEs were synthesized, varying in chain length from C₄ to C₂₀, the degree of unsaturation and also including unusual acid esters, e.g., 2E,11Z-C18:2-PCE. The latter served as a precursor of the major AHL of D. shibae DFL-12 LuxI₁, 2E,11Z-C18:2-homoserine lactone (HSL). Incubation experiments revealed that PgaI₂ accepts all substrates except C₄ and C₂₀-PCE. Competition experiments demonstrated a preference of this enzyme for C₁₀ and C₁₂ PCEs. In contrast, the LuxI enzymes of D. shibae are more selective. While 2E,11Z-C18:2-PCE is preferentially accepted by LuxI₁, all other PCEs were not, except for the shorter, saturated C₁₀–C₁₄-PCEs. The AHL synthase LuxI₂ accepted only C₁₄ PCE and 3-hydroxydecanoyl-PCE. In summary, chain-length selectivity in AHLs can vary between different AHL enzymes. Both, a broad substrate acceptance and tuned specificity occur in the investigated enzymes.

  N-酰基脱氨核糖乳酸（AHLs）是重要的细菌信使，在细胞密度依赖的方式中介导不同的细菌特征。AHLs也被许多海洋玫瑰细菌组的细菌产生，这在海洋微生物组中占据着一个大的群体。通常，细菌会产生具有不同链长和氧化状态的AHLs的特定混合物，但是生物合成酶LuxI同源物如何选择正确的酰前体大部分是未知的。我们分析了Dinoroseobacter shibae和三株Phaeobacter inhibens菌株中的AHL产生，揭示了菌株特异性混合物。尽管这些物种之间存在很大差异，但脂肪酸谱，即AHL生物合成的酰前体池，非常相似。为了测试酰链选择性，从D. shibae DFL-12的三种酶LuxI1和LuxI2以及从P. inhibens DSM 17395的PgaI2在大肠杆菌中异源表达，并将酶分离用于体外孵育实验。这些酶容易接受缩短的酰辅酶A类似物，即脂肪酸的泛酸半胱氨基乙酰硫酯（PCEs）。合成了15种PCEs，链长从C4到C20不等，不饱和度不同，还包括不寻常的酸酯，例如2E,11Z-C18:2-PCE。后者作为D. shibae DFL-12 LuxI1的主要AHL的前体，2E,11Z-C18:2-脱氨核糖乳酸（HSL）。孵育实验表明，PgaI2接受除C4和C20-PCE之外的所有底物。竞争实验表明，这种酶对C10和C12 PCE有偏好。相比之下，D. shibae的LuxI酶更具选择性。虽然2E,11Z-C18:2-PCE优先被LuxI1接受，但除了较短的饱和C10-C14-PCE之外，所有其他PCE都不被接受。AHL合酶LuxI2仅接受C14 PCE和3-羟基癸酰-PCE。总之，AHL中的链长选择性在不同的AHL酶之间可能有所不同。在研究的酶中既有广泛的底物接受性，也有调节的特异性。
• Step-Economic Synthesis of Biomimetic β-Ketopolyene Thioesters and Demonstration of Their Usefulness in Enzymatic Biosynthesis Studies
  作者：Johannes Wunderlich、Theresa Roß、Marius Schröder、Frank Hahn

  DOI：10.1021/acs.orglett.0c01348

  日期：2020.7.2

  by limited access to appropriate substrate surrogates. We present a step-economic synthetic access to biomimetic β-ketopolyene thioesters that is based on an Ir-catalyzed reductive Horner–Wadsworth–Emmons olefination. New β-ketotriene and pentaenethioates of pantetheine and N-acetylcysteamine were exemplarily synthesized via short and concise routes. The usefulness of these compounds was demonstrated

  多烯硫酯中间体的生物合成工艺研究由于难以获得合适的底物替代物而变得复杂。我们提出了一种仿生的β-酮多烯硫酯的逐步经济合成方法，该方法基于Ir催化的还原性Horner-Wadsworth-Emmons烯烃化反应。示例性地通过简短的途径合成泛酸的新的β-酮三烯和戊烯硫醚以及N-乙酰基半胱胺。这些化合物的有用性在体外测定中得到了证明，该酮还原酶结构域来自Mycolactone生物合成的MycKRB。
• [EN] PANTETHEINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGIC DISORDERS<br/>[FR] DÉRIVÉS DE PANTÉTHÉINE POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：RETROPHIN INC

  公开号：WO2018022529A1

  公开（公告）日：2018-02-01

  Compounds having the following formula (I): Formula I and pharmaceutically acceptable salts thereof, wherein A, B, D, E and R1 are as defined herein, are provided. Methods comprising the use of such compounds for the treatment of neurological disorders, such as pantothenate kinase-associated neurodegeneration, and pharmaceutical compositions containing such compounds, and their use in the treatment of neurological disorders, also are provided.

  具有以下化学式（I）：化学式I及其药用可接受的盐，其中A、B、D、E和R1如本文所定义，已提供。包括使用这些化合物治疗神经系统疾病（如泛酸激酶相关性神经退行性疾病）的方法，以及含有这些化合物的药物组合物，以及它们在治疗神经系统疾病中的用途，也已提供。
• Control of β‐Branching in Kalimantacin Biosynthesis: Application of¹³C NMR to Polyketide Programming
  作者：Paul D. Walker、Christopher Williams、Angus N. M. Weir、Luoyi Wang、John Crosby、Paul R. Race、Thomas J. Simpson、Christine L. Willis、Matthew P. Crump

  DOI：10.1002/anie.201905482

  日期：2019.9.2

  The presence of β-branches in the structure of polyketides that possess potent biological activity underpins the widespread importance of this structural feature. Kalimantacin is a polyketide antibiotic with selective activity against staphylococci, and its biosynthesis involves the unprecedented incorporation of three different and sequential β-branching modifications. We use purified single and multi-domain

  在具有强大生物活性的聚酮化合物结构中，β分支的存在加强了该结构特征的广泛重要性。卡来木霉素是一种对葡萄球菌具有选择性活性的聚酮类抗生素，其生物合成涉及三个不同且连续的β-分支修饰的空前结合。我们使用kalimantacin生物合成机制的纯化的单域和多域酶组分来解决体外如何控制kalimantacin中β分支的模式。要对酶产物进行有力的区分，就需要开发一种通用的测定方法，该方法利用结合到关键生物合成模拟物中的单个13 C标记物的13 C NMR以及酰基载体蛋白的良好动态特性。
• Stereocontrolled Syntheses of Peptide Thioesters Containing Modified Seryl Residues as Probes of Antibiotic Biosynthesis
  作者：Nicole M. Gaudelli、Craig A. Townsend

  DOI：10.1021/jo4007893

  日期：2013.7.5

  exclusion of light from the P(OEt)3-mediated Mitsunobu ring closure afforded yields of >95%, presumably owing to reduced photodegradation of the azodicarboxylate used. These sensitive potential substrates and products will be used in mechanistic studies of the two nonribosomal peptide synthetases NocA and NocB that lie at the heart of nocardicin biosynthesis, a family of monocyclic β-lactam antibiotics.

  已开发出合成三肽和五肽硫酯的方法，该硫酯含有一个或多个对-（羟苯基）甘氨酸 (pHPG) 残基和l -丝氨酸，其中一些是O-磷酸化、O-乙酰化或以 β-内酰胺形式存在. 正交保护策略的选择和条件的开发以实现 Seryl O描述了没有β-消除的-磷酸化和保持立体化学控制，特别是同时在异常碱不稳定的 pHPG α-碳上。丝氨酰肽与含 β-内酰胺肽的分子内闭合以及相应硫酯类似物的合成也有报道。在含 β-内酰胺产品的合成中描述了经典 Mitsunobu 条件的修改，并且在广泛有用的观察中，发现从 P(OEt) 3中简单地排除光介导的 Mitsunobu 环闭合提供了 >95% 的产率，这可能是由于所用偶氮二羧酸盐的光降解减少。这些敏感的潜在底物和产物将用于两种非核糖体肽合成酶 NocA 和 NocB 的机理研究，这两种非核糖体肽合成酶 Nocardicin 生物合成的核心是一个单环 β-内酰胺抗生素家族。