hydroxocobalamin | 13422-51-0

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: hydroxocobalamin
• 英文别名: hydroxycobalamin；cobalt(3+);[(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2R)-1-[3-[(1R,2R,3R,7S,12S,13S,17S,18S,19R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-21-id-3-yl]propanoylamino]propan-2-yl] phosphate;hydroxide
• CAS: 13422-51-0
• 化学式: C₆₂H₈₉CoN₁₃O₁₅P
• 分子量: 1346.43
• InChiKey: YOZNUFWCRFCGIH-WZHZPDAFSA-K

物化性质

• 熔点：
  >300 °C
• 溶解度：
  甲醇：10 mg/mLat 20 °C，澄清，暗红色
• LogP：
  -2.812 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Dark red, orthorhombic needles or platelets from water and acetone
• 气味：
  ODORLESS OR HAS NOT MORE THAN SLIGHT ACETONE ODOR
• 蒸汽压力：
  2.06X10-11 mm Hg at 25 °C
• 颜色/状态：
  Dark red, orthorhombic needles or platelets from water and acetone

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  92
• 可旋转键数：
  26
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  453
• 氢给体数：
  10
• 氢受体数：
  20

ADMET

代谢

羟钴胺的毒物动力学在大鼠和犬类中进行了单次给药后的研究。在犬类中，自由钴胺-(III)和总钴胺-(III)的药时曲线下面积（AUC）与剂量成正比增加。自由钴胺-(III)和总钴胺-(III)的平均最大血药浓度（Cmax）是人类接受5.0和10.0克羟钴胺治疗时的1到5倍。自由钴胺-(III)和总钴胺-(III)的终末半衰期在犬类中分别达到大约6和8小时。在大鼠中，相应的数字为3和5小时。在犬类中，总钴胺-(III)的清除率（0.064至0.083 L/h/kg）是自由钴胺-(III)清除率的6-7倍。

Toxicokinetics of hydroxocobalamin were studied in rats and in dogs after single administration. In dogs, the AUCs of free cobalamins-(III) and total cobalamins-(III) increased proportionally to the dose. Mean Cmax measured for free- and total cobalamins-(III) were 1 to 5 fold higher than those measured in humans treated with 5.0 and 10.0 g hydroxocobalamin. Terminal half-lives reached approximately 6 and 8 hours for free and total cobalamins-(III), respectively in dogs. Corresponding figures in rats amounted to 3 and 5 hours. In dogs, the clearance of total cobalamins-(III) (0.064 to 0.083 L/h/kg) was 6-7 fold lower than clearance of free cobalamins-(III).

来源:Hazardous Substances Data Bank (HSDB)

代谢

羟钴胺与蛋白质的结合可以被认为是可逆的代谢。羟钴胺还会与氰化物反应，从而形成氰钴胺。这个复合物非常稳定，因此被认为是羟钴胺的生理终产物，尤其是在氰化物中毒期间。

The binding of hydroxocobalamin to proteins may be regarded as reversible metabolism. Hydroxocobalamin also reacts with cyanide thereby forming cyanocobalamin. This complex is highly stable and is therefore regarded as a physiological end product of hydroxocobalamin especially during cyanide intoxication.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

据报道，氯霉素和维生素B12的联合使用可能会拮抗维生素B12在维生素B12缺乏患者中的造血反应。在接受这两种药物的患者中，应对维生素B12的血液学反应进行仔细监测，并考虑使用其他抗感染药物。/维生素B12/

Concurrent administration of chloramphenicol and vitamin B12 reportedly may antagonize the hematopoietic response to vitamin B12 in vitamin B12-deficient patients. The hematologic response to vitamin B12 in patients receiving both drugs should be carefully monitored and alternate anti-infectives should be considered. /Vitamin B12/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

泼尼松在少数患有恶性贫血的患者中已被报告能增加维生素B12的吸收和内因子（IF）的分泌，但在部分或全部胃切除的患者中并未发现此现象。这些发现的临床重要性尚不清楚。/维生素B12/

Prednisone has been reported to increase the absorption of vitamin B12 and secretion of intrinsic factor (IF) in a few patients with pernicious anemia, but not in patients with partial or total gastrectomy. The clinical importance of these findings is unknown. /Vitamin B12/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

维生素C可能会在体外破坏大量的膳食维生素B12；当摄入大剂量的维生素C，并且与口服维生素B12的服用时间相隔不超过1小时时，应考虑这种可能性。/维生素B12/

Ascorbic acid may destroy substantial amounts of dietary vitamin B12 in vitro; this possibility should be considered when large doses of ascorbic acid are ingested within 1 hour of oral vitamin B12 administration. /Vitamin B12/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

从胃肠道吸收维生素B12可能会因氨基糖苷类抗生素、秋水仙碱、缓释钾制剂、氨基水杨酸及其盐类、抗惊厥药（例如：苯妥英、苯巴比妥、普里米酮）、小肠钴照射以及超过两周的过量饮酒而降低。同时使用秋水仙碱可能会增加新霉素引起的维生素B12吸收不良。/维生素B12

Absorption of vitamin B12 from the GI tract may be decreased by aminoglycoside antibiotics, colchicine, extended-release potassium preparations, aminosalicylic acid and its salts, anticonvulsants (e.g., phenytoin, phenobarbital, primidone), cobalt irradiation of the small bowel, and by excessive alcohol intake lasting longer than 2 weeks. Neomycin-induced malabsorption of vitamin B12 may be increased by concurrent administration of colchicine. /Vitamin B12

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在同时使用Cyanokit和其他氰化物解毒剂时应谨慎，因为尚未确立共同给药的安全性。如果决定在使用Cyanokit的同时给予另一种氰化物解毒剂，这些药物不应在同一静脉输液管路中同时给药。

Caution should be exercised when administering other cyanide antidotes simultaneously with Cyanokit, as the safety of coadministration has not been established. If a decision is made to administer another cyanide antidote with Cyanokit, these drugs should not be administered concurrently in the same IV line.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中进行了一项研究，调查了经鼻腔给药后羟钴胺从鼻腔直接运输到脑脊液的可能性，并将结果与人类研究进行了比较。羟钴胺通过鼻腔（214微克/只）和颈静脉血管接入端口（VAP）静脉注射（49.5微克/只）给予大鼠（n=8）。在给药前后取血和脑脊液样本，并通过放射免疫分析进行检测。经鼻腔给药后脑脊液/血浆的AUC比率与静脉输注后的比率没有差异，这表明羟钴胺通过血液循环穿过血脑屏障（BBB）进入脑脊液。这一相同的运输路线在大鼠和人类研究中通过脑脊液和血浆的累积AUC-时间剖面得到了证实，显示出羟钴胺在血浆吸收和脑脊液摄取之间存在30分钟的延迟。目前在大鼠中的结果表明，与静脉给药相比，经鼻腔给药后脑脊液中没有额外的羟钴胺摄取，这与人类研究的结果一致。

The possibility of direct transport of hydroxocobalamin from the nasal cavity into the cerebrospinal fluid after nasal administration in rats was investigated and the results were compared with a human study. Hydroxocobalamin was given to rats (n=8) both intranasally (214 ug/rat) and intravenously (49.5 ug/rat) into the jugular vein using a Vascular Access Port (VAP). Prior to and after drug administration, blood and cerebrospinal fluid samples were taken and analysed by radioimmunoassay. The AUCcerebrospinal fluid/AUCplasma ratio after nasal delivery does not differ from the ratio after intravenous infusion, indicating that hydroxocobalamin enters the cerebrospinal fluid via the blood circulation across the blood-brain barrier (BBB). This same transport route is confirmed by the cumulative AUC-time profiles in cerebrospinal fluid and plasma, demonstrating a 30 min delay between plasma absorption and cerebrospinal fluid uptake of hydroxocobalamin in rats and in a comparative human study. The present results in rats show that there is no additional uptake of hydroxocobalamin in the cerebrospinal fluid after nasal delivery compared to intravenous administration, which is in accordance with the results found in humans.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

50%的氢氧钴胺素剂量在2.5小时内从注射部位消失。氢氧钴胺素与血浆蛋白结合并在肝脏中储存。它通过胆汁排出，并经历一些肠肝循环。在注射500到1000微克氢氧钴胺素后的72小时内，16%到66%的注射剂量可能会出现在尿液中。大部分在最初的24小时内排出。

Fifty percent of the administered dose of hydroxocobalamin disappears from the injection site in 2.5 hours. Hydroxocobalamin is bound to plasma proteins and stored in the liver. It is excreted in the bile and undergoes some enterohepatic recycling. Within 72 hours after injection of 500 to 1000 mcg of hydroxocobalamin, 16 to 66 percent of the injected dose may appear in the urine. The major portion is excreted within the first 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

羟钴胺素从注射部位的吸收速度比氰钴胺素慢，并且有证据表明羟钴胺素在肝脏的摄取可能大于氰钴胺素。人们认为，与氰钴胺素相比，羟钴胺素在血液和组织中的特定和非特异性结合蛋白的亲和力更强，以及从注射部位吸收更慢，这导致了羟钴胺素较氰钴胺素有更高的保留率。

Hydroxocobalamin is absorbed more slowly from the site of injection than is cyanocobalamin and there is some evidence that liver uptake of hydroxocobalamin may be greater than that of cyanocobalamin. It is believed that the increased retention of hydroxocobalamin compared with that of cyanocobalamin results from the greater affinity of hydroxocobalamin for both specific and nonspecific binding proteins in blood and tissues, as well as to its slower absorption from the injection site.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在胃酸和胰腺蛋白水解酶的作用下，饮食中的维生素B12从食物和唾液结合蛋白中释放出来，并与胃内源因子结合。当维生素B12-内源因子复合物到达回肠时，它与粘膜细胞表面的受体相互作用，并积极进入循环。充足的内在因子、胆汁和碳酸氢钠（以提供适宜的pH值）都是回肠运输维生素B12所必需的。成人维生素B12缺乏很少是因为饮食本身不足；相反，它通常反映出这个复杂吸收序列的一个或另一个方面的缺陷。胃酸缺乏和由于胃萎缩或胃手术导致的壁细胞内源因子分泌减少是成人维生素B12缺乏的常见原因。对壁细胞或内源因子复合物的抗体也在产生缺乏症中发挥重要作用。许多肠道疾病都可能干扰吸收，包括胰腺疾病（胰腺蛋白水解酶分泌丧失）、细菌过度生长、肠道寄生虫、热带口炎性腹泻和疾病或手术导致的回肠粘膜细胞局部损伤。/维生素B-12/

In the presence of gastric acid and pancreatic proteases, dietary vitamin B12 is released from food and salivary binding protein and bound to gastric intrinsic factor. When the vitamin B12-intrinsic factor complex reaches the ileum, it interacts with a receptor on the mucosal cell surface and is actively transported into circulation. Adequate intrinsic factor, bile, and sodium bicarbonate (to provide a suitable pH) all are required for ileal transport of vitamin B12. Vitamin B12 deficiency in adults is rarely the result of a deficient diet per se; rather, it usually reflects a defect in one or another aspect of this complex sequence of absorption. Achlorhydria and decreased secretion of intrinsic factor by parietal cells secondary to gastric atrophy or gastric surgery is a common cause of vitamin B12 deficiency in adults. Antibodies to parietal cells or intrinsic factor complex also can play a prominent role in producing a deficiency. A number of intestinal diseases can interfere with absorption, including pancreatic disorders (loss of pancreatic protease secretion), bacterial overgrowth, intestinal parasites, sprue, and localized damage to ileal mucosal cells by disease or as a result of surgery. /Vitamin B-12/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 危险品运输编号：
  NONH for all modes of transport
• 储存条件：
  | 温度范围：2-8°C |

SDS

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Section 1. Chemical Product and Company Identification
Hydroxocobalamin
Common Name/
Trade Name
Hydroxocobalamin

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Section 4. First Aid Measures
Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at
least 15 minutes. Cold water may be used. Get medical attention.
Skin Contact In case of contact, immediately flush skin with plenty of water. Cover the irritated skin with an emollient. Remove
contaminated clothing and shoes. Cold water may be used.Wash clothing before reuse. Thoroughly clean shoes
before reuse. Get medical attention.
Serious Skin Contact Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek medical
attention.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Ingestion Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
Serious Ingestion Not available.

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash Points Not available.
Flammable Limits Not available.
Products of Combustion These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...). Some metallic oxides.
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances Non-flammable in presence of shocks.
Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available.
of Various Substances 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.
Special Remarks on Not available.
Fire Hazards
Special Remarks on Explosion Not available.
Hazards

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Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
Hydroxocobalamin

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Section 7. Handling and Storage
Precautions Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the
residue under a fume hood. Ground all equipment containing material. Do not breathe dust. Wear suitable
protective clothing. In case of insufficient ventilation, wear suitable respiratory equipment. If you feel unwell, seek
medical attention and show the label when possible. Avoid contact with skin and eyes.
Storage Keep container tightly closed. Keep container in a cool, well-ventilated area. Do not store above 15°C (59°F).

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Section 8. Exposure Controls/Personal Protection
Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent.
Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spill to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist
BEFORE handling this product.
Exposure Limits Not available.

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Section 9. Physical and Chemical Properties
Physical state and appearance Solid. Odor Odorless or has not more than slight acetone
odor
Taste Not available.
Molecular Weight 1346.38 g/mole
Color Red.
pH (1% soln/water) Not available.
Boiling Point Not available.
Melting Point Not available.
Critical Temperature Not available.
Not available.
Specific Gravity
Vapor Pressure Not applicable.
Vapor Density Not available.
Volatility Not available.
Odor Threshold Not available.
Water/Oil Dist. Coeff. Not available.
Ionicity (in Water) Not available.
See solubility in water.
Dispersion Properties
Solubility Soluble in cold water.
Insoluble in diethyl ether, acetone.

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Instability Temperature Not available.
Elevated temperatures, light, incompatible materials
Conditions of Instability
Incompatibility with various Not available.
substances
Hydroxocobalamin
Not available.
Corrosivity
Special Remarks on Light sensitive.
Reactivity
Special Remarks on Not available.
Corrosivity
Will not occur.
Polymerization

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Section 11. Toxicological Information
Routes of Entry Inhalation. Ingestion.
Toxicity to Animals LD50: Not available.
LC50: Not available.
Chronic Effects on Humans Not available.
Other Toxic Effects on Hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Slightly hazardous in case of skin contact (sensitizer).
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on Crosses the placenta from mother to fetus
Chronic Effects on Humans
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation. May cause allergic reactions.
Inhalation: Dust May cause respiratory tract irritation.
Eyes: Dust may cause eye irritation.
Ingestion: May cause digestive tract irritation.
The toxicological properties of this substance have not been fully investigated.

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Section 12. Ecological Information
Ecotoxicity Not available.
BOD5 and COD Not available.
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
Toxicity of the Products The product itself and its products of degradation are not toxic.
of Biodegradation
Special Remarks on the Not available.
Products of Biodegradation

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Section 13. Disposal Considerations
Waste Disposal Waste must be disposed of in accordance with federal, state and local environmental
control regulations.
Hydroxocobalamin

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Section 14. Transport Information
DOT Classification Not a DOT controlled material (United States).
Identification Not applicable.
Not applicable.
Special Provisions for
Transport
DOT (Pictograms)

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Section 15. Other Regulatory Information and Pictograms
TSCA 8(b) inventory: Hydroxocobalamin
Federal and State
Regulations
California
Proposition 65
Warnings
Other Regulations EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
DSCL (EEC) R36/38- Irritating to eyes and skin. S2- Keep out of the reach of children.
S46- If swallowed, seek medical advice
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.) 2 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
2 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Hydroxocobalamin
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

羟钴胺素是合成硝基钴胺素和醋酸钴胺素的重要中间体，并且也是维生素B12的一种生理类似物，其中CN基团被OH取代。在水溶液中，它以羟基异构体和离子水异构体（aquacobalamin）的平衡混合物形式存在。此外，羟钴胺素还是辅酶甲基钴胺素及钴胺素的前体，并且具有配位化合物的特性。

作为一种维生素，羟钴胺素对造血有重要作用。

概述

注射用羟钴胺是一种安全无毒、迅速起效的新一代氰化物解毒剂，商品名为Cyanokit。该产品由法国EMD制药公司生产并提供原料，而美国DeyLaboratories公司则负责包装和销售。

这种药物主要用于治疗恶性贫血及其他因缺乏维生素B12引起的病症。在大剂量使用时，它还可以作为氰化物的解毒剂，将氰化物转化为无害的氰钴胺。

反应信息

• 作为反应物：
  描述：

  hydroxocobalamin 在 sodium tetrahydroborate 、 水 作用下， 生成 cob(II)alamine
  参考文献：
  名称：

  叔丁基过氧化氢和过氧化氢在水溶液中减少钴胺素失活的自由基机理与离子机理

  摘要：

  还原钴胺素（Cbl（II）），还原钴胺素与SO 2 - ˙自由基阴离子（B 12rs，SO 2 - Cbl（II））和超还原钴胺素（B 12s，Cbl）的反应的比较研究（I）用过氧化氢（H 2 O 2）和叔丁基过氧化氢（t BuOOH）在厌氧条件下在水溶液中进行。反应产物的分析表明维生素B的钴（III）丙氨酸（Cbl（III））和内消旋羟基化衍生物H 12 O 2与Cbl（ II）和SO 2 - Cbl（ II）反应的主要有色产物为12（稳定的黄色类海藻素，SYC）。与H 2 O 2相比，Cbl（ III）是还原的钴胺素与t BuOOH反应的唯一有色产物。两种过氧化物均与超还原钴胺素以[（Cbl（ I））]：[过氧化物] = 2：1的比例反应形成Cbl（ II）。基于对形成Cbl（ II）氧化产物的可能反应途径的比较，我们得出结论，Cbl（ II）碳负离子是过氧化氢与Cbl（II）在水溶液

  DOI：

  10.1039/d0nj04231e
• 作为产物：
  描述：

  生成 hydroxocobalamin
  参考文献：
  名称：

  CARAMICO, SOARES, I.;FERNANDES, MAGALHAES, J., REV. FARM. E BIOQUIM. UNIV. SAO PAULO, 1984, 20, N 1, 1-16

  摘要：

  DOI：
• 作为试剂：
  描述：

  S-腺苷蛋氨酸 在 hydroxocobalamin 、 DL-dithiothreitol 、 methyl aminocyclopropanecarboxylic acid (Orf₃₀) 、 S-adenosyl-L-methionine methylase (Orf₂₉) 、 还原型辅酶Ⅰ 作用下， 生成 (+)-(1S,2S)-norcoronamic acid
  参考文献：
  名称：

  1-氨基-2-甲基环丙烷甲酸生物合成中钴胺素依赖性自由基 S-腺苷-L-蛋氨酸甲基化酶对 S-腺苷-L-蛋氨酸 C-甲基化的机制

  摘要：

  自由基S-腺苷-l-甲硫氨酸 (SAM) 甲基化酶 Orf29在 1-氨基-2-甲基环丙烷甲酸的生物合成中催化SAM 的C-甲基化。在这里，我们确定甲基化产物是(4″ R )-4″-甲基-SAM。此外，我们发现Orf29产生的5′-脱氧腺苷自由基从SAM的C-4”位上夺取pro-R氢原子，生成自由基中间体，该自由基中间体与甲钴胺反应生成(4” R )-4” -甲基-SAM。因此，证实Orf29催化的C-甲基化在构型保留的情况下进行。

  DOI：

  10.1021/acs.orglett.2c03555

文献信息

• Mechanistic Studies on CysS – A Vitamin B₁₂-Dependent Radical SAM Methyltransferase Involved in the Biosynthesis of the <i>tert</i>-Butyl Group of Cystobactamid
  作者：Yuanyou Wang、Tadhg P. Begley

  DOI：10.1021/jacs.9b06454

  日期：2020.6.3

  Cobalamin (Cbl)-dependent radical SAM methyltransferases catalyze methylation reactions at non-nucleophilic centers in a wide range of substrates. CysS is a Cbl-dependent radical SAM methyltransferase involved in cystobactamid biosynthesis. This enzyme catalyzes the sequential methylation of a methoxy group to form ethoxy, i-propoxy, s-butoxy, and t-butoxy groups on a p-aminobenzoate peptidyl carrier

  钴胺素 (Cbl) 依赖性自由基 SAM 甲基转移酶可在多种底物的非亲核中心催化甲基化反应。CysS 是一种 Cbl 依赖性自由基 SAM 甲基转移酶，参与cysobactamid 生物合成。该酶催化甲氧基的顺序甲基化，在对氨基苯甲酸肽基载体蛋白硫酯中间体上形成乙氧基、异丙氧基、仲丁氧基和叔丁氧基。这种生物合成策略使宿主粘杆菌能够生物合成 25 种囊菌酰胺类似物的组合抗生素文库。在本文中，我们描述了三个实验来阐明 CysS 如何使用 Cbl、SAM 和 [4Fe-4S] 簇来催化迭代甲基化反应：环丙基羰基重排用于捕获底物自由基并估计参与甲基转移的自由基取代反应的速率；溴乙氧基类似物用于探索活性位点地形；和氘同位素对腺苷自由基提取氢原子的影响被用来研究氢原子提取的动力学意义。基于这些实验，提出了一种修正的 CysS 机制。
• Fluorophore Assisted Photolysis of Thiolato-Cob(III)alamins
  作者：Zachary L. Rodgers、Thomas A. Shell、Alexander M. Brugh、Hannah L. Nowotarski、Malcolm D. E. Forbes、David S. Lawrence

  DOI：10.1021/acs.inorgchem.5b02036

  日期：2016.3.7

  investigated the photolysis of N-acetylcysteinyl cob(III)alamin at several wavelengths within the ultraviolet and visible spectrum. To aid in photolysis, we show that attaching fluorophore “antennae” to the cobalamin scaffold can improve photolytic efficiency by up to an order of magnitude. Additionally, electron paramagnetic resonance confirms previous conjectures that the photolysis of thiolato-cobalamins

  已知钴胺素会与硫醇反应，生成稳定的β轴Co III –S键合硫代巯基-钴胺素复合物。但是，与烷基钴胺素中的Co-C键形成鲜明对比的是，硫醇盐-钴胺素中的Co-S键的可光化性仍未确定。我们已经研究了N-乙酰半胱氨酰钴（III）丙氨酸在紫外和可见光谱内的几个波长上的光解作用。为了有助于光解，我们表明将荧光团“天线”连接到钴胺素支架上可以将光解效率提高一个数量级。此外，电子顺磁共振证实了以前的推测，即硫羟钴胺素在长达546 nm的波长处发生光解会产生噻吩基。
• Studies on Vitamin B₁₂ and Related Compounds, 51 [1] Direct Syntheses of Alkylcobalamins from Alkanes and Vitamin B_12r under "Oxidizing-Reducing" Conditions
  作者：Abdussalam Maihub、Hui Bi Xu、Gerhard N. Schrauzer

  DOI：10.1515/znb-1980-1122

  日期：1980.11.1

  n-alkylcobalamins from n-alkanes (C2→C10) and vitamin B12r are described. The compounds are formed under "oxidizing-reducing" conditions: Oxygen radicals (O2-, HOO·, and HO·) are generated from the reaction of O2 with reducing metal ions, notably V+3 (aq) and abstract hydrogen from the alkane substrates. The resulting alkyl radicals are captured by vitamin Bj2r with high efficiency to yield alkylcobalamins

  摘要描述了从甲烷合成甲基钴胺素，以及从正烷烃 (C2→C10) 和维生素 B12r 合成正烷基钴胺素。这些化合物是在“氧化-还原”条件下形成的：氧自由基（O2-、HOO·和 HO·）是由 O2 与还原性金属离子（特别是 V+3 (aq)）反应生成的，并从烷烃中提取氢基材。生成的烷基自由基被维生素 Bj2r 高效捕获以产生烷基钴胺素。反应在室温下在弱碱性或酸性溶液中进行。除了正烷基钴胺素之外，还报道了从新戊烷制备新戊基钴胺素、从异丁烷制备异丁基钴胺素和从环烷烃制备几种环烷基钴胺素的方法。在“氧化-还原”条件下由 CH4 在 D2O 中生成的甲基自由基
• Studies on Vitamin B₁₂ and Related Compounds, 50 Synthesis of Substituted Alkylcobalamins from Vitamin B_12r and Radicals Generated from Aldehydes, Alcohols and Ethers under "Oxidizing-Reducing" Conditions. A New Synthesis of Coenzyme B₁₂ [1]
  作者：Gerhard N. Schrauzer、Masao Hashimoto、Abdussalam Maihub

  DOI：10.1515/znb-1980-0515

  日期：1980.5.1

  Organic radicals generated by the oxidation of aldehydes, alcohols and ethers under reducing conditions are trapped by vitamin B12r to yield substituted organocobalamins. From higher n-alkyl aldehydes, acylcobalamins are formed. With acetaldehyde, a mixture of acetylcobalamin and of methylcobalamin is obtained due to the spontaneous decarbonylation of the CH3CO· radical. From saturated alcohols, w

  醛、醇和醚在还原条件下氧化产生的有机自由基被维生素 B12r 捕获，产生取代的有机钴胺素。由高级正烷基醛形成酰基钴胺素。使用乙醛，由于 CH3CO· 自由基的自发脱羰，得到乙酰钴胺素和甲基钴胺素的混合物。由饱和醇生成正羟基烷基钴胺素，而正构烷氧基烷基钴胺素在与醚生成的自由基的相应反应中形成。如果在有机底物氧化过程中保持还原条件，则可获得最大的有机钴胺素产量。这可以通过使用 V(III) 盐作为还原剂和缓慢加入氧化剂（例如 O2、H2O2、芬顿试剂、或电化学产生的氧化等效物）。与 5'-脱氧腺苷一起形成 5'-脱氧腺苷钴胺素。
• Carboxyalkylcobalamins: Effects of Carboxyl Substituents on Base-on / Base-off Equilibria and Mechanochemical Co–C Bond Cleavage
  作者：Gerhard N. Schrauzer、Mary L. Maciejewski-Mattson

  DOI：10.1515/znb-2008-0206

  日期：2008.2.1

  A series of primary and secondary carboxyalkylcobalamins with (CH2)nCOOH groups (n = 1 - 3), CH2-CH(CH3)COOH, CH(R)COOH (R = CH3, C2H5, n-C3H7), CH(CH3)(CH2)nCOOH (n = 1, 2) and CH(COOH)CH2COOH attached to cobalt were synthesized or generated in situ, mostly by the reaction of vitamin B12s or hydridocobalamin with the respective α- or ω-substituted halocarboxylic acids and reactions with olefinic carboxylic

  一系列具有 (CH2)nCOOH 基团 (n = 1 - 3)、CH2-CH(CH3)COOH、CH(R)COOH (R = CH3、C2H5、n-C3H7)、CH(CH3) 的伯和仲羧烷基钴胺素与钴相连的 (CH2)nCOOH (n = 1, 2) 和 CH(COOH)CH2COOH 是原位合成或生成的，主要是通过维生素 B12s 或氢化钴胺素与相应的 α- 或 ω- 取代的卤代羧酸的反应以及与烯烃羧酸或二羧酸。它们的分解速率和活化参数 ΔGo≠ 、ΔHo≠ 和 ΔSo≠ Co-C 键断裂在不同 pH 值的水溶液中通过分光光度法测定。羧烷基钴胺素在溶液中通常比可比较的未取代的烷基钴胺素更稳定。在仲 1-羧基烷基钴胺素中，这主要归因于诱导效应和羧基的较小尺寸。羧基的存在也加强了钴与 5,6-二甲基苯并咪唑 (DMBZ) 配体的轴向相互作用，这通过测量这些有机钴胺素中 DMBZ 的 pKa