57333-96-7

• 常用中文名：他卡西妥
• 常用英文名：Tacalcitol
• CAS号：57333-96-7
• 分子式：C₂₇H₄₄O₃
• 分子量：416.637
• 相关类别： 信号通路 维生素 D 相关 VD/VDR
• 发布时间：2018-02-22 08:00:00
• 更新时间：2024-01-02 20:16:05
• Tacalcitol (1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3) 能通过调节钙离子促进正常骨生长。

名称

• 中文名: 他卡西妥
• 英文名: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,5R)-5-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
• 中文别名: (1Α,3Β-5Z,7E,24R)-9,10-开环胆甾-5,7,10(19)-三烯-1,3,24-三醇; 他卡西醇; (1A,3B,5Z,7E,24R)-9,10-开环胆甾-5,7,10(19)-三烯-1,3,24-三醇
• 英文别名: 1a,24R-Dihydroxyvitamin D3; TV-02H; 1,3-Cyclohexanediol, 4-methylene-5-[(2E)-2-[(1R,3aS,7aR)-octahydro-1-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-7a-methyl-4H-inden-4-ylidene]ethylidene]-, (1R,3S,5Z)-; (1S,3R,5Z,7E,24R)-9,10-Secocholesta-5,7,10-triene-1,3,24-triol; Bonalfa; 1a,24(R)-Dihydroxycholecalciferol; Curatoderm; (1a,3b,5Z,7E,24R)-9,10-Secocholesta-5,7,10(19)-triene-1,3,24-triol; 1,24R-dihydroxyvitamin D3; TV-02; (+)-(5Z,7E,24R)-9,10-Secocholesta-5,7,10(19)-triene-1α,3β,24-triol; Tacalcitol

物化性质

• 密度: 1.1±0.1 g/cm3
• 沸点: 565.0±50.0 °C at 760 mmHg
• 分子式: C₂₇H₄₄O₃
• 分子量: 416.637
• 闪点: 238.4±24.7 °C
• 精确质量: 416.329041
• PSA: 60.69000
• LogP: 6.12
• 蒸汽压: 0.0±3.5 mmHg at 25°C
• 折射率: 1.546
• 储存条件: Store at -20°C
• 分子结构:

  1、 摩尔折射率：124.30

  2、 摩尔体积（cm³/mol）：392.7

  3、 等张比容（90.2K）：1009.4

  4、 表面张力（dyne/cm）：43.6

  5、 极化率（10-24cm3）：49.27

• 计算化学:

  1.疏水参数计算参考值（XlogP）:5.3

  2.氢键供体数量:3

  3.氢键受体数量:3

  4.可旋转化学键数量:6

  5.互变异构体数量:无

  6.拓扑分子极性表面积60.7

  7.重原子数量:30

  8.表面电荷:0

  9.复杂度:676

  10.同位素原子数量:0

  11.确定原子立构中心数量:7

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:2

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1.性状：白色固体。

  2.UV最大吸收(乙醇)：265nm。

生物活性

• 描述: Tacalcitol (1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3) 能通过调节钙离子促进正常骨生长。
• 相关类别:
  信号通路 >> 维生素 D 相关 >> VD/VDR
  研究领域 >> 代谢疾病
• 参考文献:

  [1]. Masuo Morisaki , aoyuki Koizumi , Nobuo Ikekawa et al. Synthesis of active forms of vitamin D. Part IX. Synthesis of 1α,24-dihydroxycholecalciferol. J. Chem. Soc., Perkin Trans. 1, 1975, 1421-1424

  [2]. Kiyoshige Ochi , Isao Matsunaga , Hiroyuki Nagano et al. Synthetic studies of vitamin D3 analogues from bile acids. Part 3. Syntheses of 1α,25-, 1α,24R-, and 1α,24S-dihydroxycholecalciferols from lithocholic acid and their biological activities. J. Chem.

  [3]. Rostowska-Nadolska et al Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblasts. Adv.Med.Sci. (2010) 55 86.

  [4]. Oiso N, Kawada A.Freckling Promoted by Topical Tacalcitol in a Japanese Boy with Left Eyelid Vitiligo.Pediatr Dermatol. 2011 Oct 20.

  [5]. Kobayashi T, Okumura H, Azuma Y, Kiyoki M, Matsumoto K, Hashimoto K, Yoshikawa K.1 alpha,24R-dihydroxyvitamin D3 has an ability comparable to that of 1 alpha,25-dihydroxyvitamin D3 to induce keratinocyte differentiation.J Dermatol. 1990 Nov;17(11):707-9.

  [6]. Matsumoto K, Hashimoto K, Kiyoki M, Yamamoto M, Yoshikawa K.Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.J Dermatol. 1990 Feb;17(2):97-103.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : VS2882200 CHEMICAL NAME : 9,10-Secocholesta-5,7,10(19)-triene-1,3,24-triol, (1-alpha,3-beta,5Z,7E,24R)- CAS REGISTRY NUMBER : 57333-96-7 LAST UPDATED : 199806 DATA ITEMS CITED : 7 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3279 ug/kg TOXIC EFFECTS : Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 100 ug/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain Skin and Appendages - hair Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 556 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Skin and Appendages - hair Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3050 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 419 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 559 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 10 ug/kg TOXIC EFFECTS : Behavioral - food intake (animal) Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - changes in calcium REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17,4615,1989

安全

• 符号: GHS06
• 信号词: Danger
• 危害声明: H300
• 危害码 (欧洲): N-T+
• 风险声明 (欧洲): R50/53:Very Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment . R33:Danger of cumulative effects. R26/27/28:Very Toxic by inhalation, in contact with skin and if swallowed .
• 安全声明 (欧洲): S61-S60-S45-S36-S28A-S13
• 危险品运输编码: 2025
• RTECS号: OW2300000
• 包装等级: II
• 危险类别: 6.1

制备

889.5mg化合物(Ⅰ)溶于30ml二甲亚砜，加入叔丁醇钾(从0.5g钾制得)，在氩气下于20℃反应30min。倾入冰水，用乙醚提取。提取液用水洗，干燥，浓缩。残物溶于乙醚，在-10℃或以下，将其滴到硼氢化钙和氯化钙在甲醇的溶液中，再在-10℃搅拌1h。用乙酸水溶液破坏过量的硼氢化钙，然后浓缩，再用二氯甲烷提取。提取液水洗，干燥，浓缩。残物溶于二氯甲烷，分小批量加入化合物(Ⅱ)。加毕，在室温搅拌1h。蒸出溶剂，残物经硅胶层析，以1%甲醇的氯仿溶液洗脱，得400.35mg化合物(Ⅲ)。
400.35mg化合物(Ⅲ)溶于氯仿，加入间氯过苯甲酸，在25℃搅拌40h。反应液用碳酸钾水溶液和水洗，干燥，浓缩。残物经硅胶层析，以1%甲醇的氯仿溶液洗脱，得170.6mg化合物(Ⅳ)。
83.0mg化合物(Ⅳ)溶于干燥四氢呋喃，小批量加入氢化铝锂，温和回流1h。加入硫酸钠以破坏过量的氢化铝锂。分出有机层，干燥，浓缩。残物经SephadexLH-20层析提纯，以氯仿-己烷(65：35体积比)洗脱，得到21.3mg化合物(V)。
21.3mg化合物(V)溶于乙醚，以400W高压汞灯照射，在照射中通过通入氩气来搅拌。浓缩，残物经SephadexLH-20层析，以氯仿-己烷(65：35体积比)洗脱，得3.64mg产物。