1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene | 103909-78-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene
• 英文别名: (1S,3R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-20-(3-hydroxy-3-methylbuthyloxy)pregna-5,7-dien；(1S,3R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-20-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene；1α,3β-bis(t-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene；1α,3β-bis(t-butyldimethylsilyloxy)-20S-(3-methyl-3-hydroxybutyloxy)-5,7-pregnadiene；4-[(1S)-1-[(1S,3R,9S,10R,13S,14R,17S)-1,3-bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]ethoxy]-2-methylbutan-2-ol
• CAS: 103909-78-0
• 化学式: C₃₈H₇₀O₄Si₂
• 分子量: 647.142
• InChiKey: YUUWCAFTWNPDKO-QTNJQGLXSA-N

物化性质

• 熔点：
  146 °C
• 沸点：
  629.9±55.0 °C(Predicted)
• 密度：
  0.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.44
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 17.02h， 生成 马沙骨化醇
  参考文献：
  名称：

  Synthesis of tritiated 1α,25-dihydroxy-22-oxavitamin D3

  摘要：

  描述了两种氚标记的1α,25-二羟基-22-氧维生素D3（OCT），即[26-3H3]OCT (3)和[2β-3H]OCT (4)的合成。[26-3H3]OCT (3)是通过用氚标记的甲基镁碘化物对侧链进行氚标记而制备的，而[2β-3H]OCT (4)则是通过与硼氚化钠进行氚标记在A环上标记的。

  DOI：

  10.1002/jlcr.2580360706
• 作为产物：
  描述：

  (1S,3R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-20-(3-hydroxy-3-methylbuthyloxy)pregn-5-ene 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 2,4,6-三甲基吡啶 作用下， 以 正己烷 、 甲苯 为溶剂， 以7.08 g的产率得到1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutyloxy)pregna-5,7-diene
  参考文献：
  名称：

  一种马沙骨化醇的制备方法

  摘要：

  本发明涉及一种药物的合成方法，特别涉及一种马沙骨化醇的制备方法。以脱氢表雄酮为起始原料，经酰化、格氏反应、氧化、皂化、羟基保护、环氧化、还原、消除、NBS溴代/脱溴化氢、脱保护基、光照开环制备得到马沙骨化醇，操作简单、收率高，适合大规模工业化生产。

  公开号：

  CN114656385A

文献信息

• Practical Formation of γ-Keto or γ-Hydroxy Ether Linkage from Alcohol¹
  作者：Tetsuhiro Mikami、Tomoyasu Iwaoka、Masahiro Kato、Hiroyoshi Watanabe、Noboru Kubodera

  DOI：10.1080/00397919708004097

  日期：1997.7

  Abstract A practically useful formation of γ-keto or γ-hydroxy ether linkage from alcohol, for the construction of the side chain of 1α, 25-dihydroxy-22-oxavitamin D3 (OCT), is described.

  摘要描述了从醇中形成 γ-酮或 γ-羟基醚键的实用方法，用于构建 1α, 25-二羟基-22-氧维生素 D3 (OCT) 的侧链。
• 22-oxacholecalciferol derivative and process for preparing the same
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05436401A1

  公开（公告）日：1995-07-25

  A 22-oxacholecalciferol derivative represented by formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom or a hydroxyl group; and R.sub.2 and R.sub.3, which may be the same or different, each represent a lower alkyl group having from 1 to 5 carbon atoms, and a process for preparing the same are disclosed. The compound of the present invention has potent differentiation inducing activity and cell proliferation inhibitory activity and is expected to be useful as an anti-tumor agent, an antirheumatic, a treating agent for psoriasis, and a treating agent for hyperparathyreosis. The process of the present invention makes it possible to efficiently produce a desired 22-oxacholecalciferol derivative while reducing by-production.

  本发明公开了一种由公式（I）表示的22-氧合胆钙化醇衍生物：##STR1## 其中R.sub.1代表氢原子或羟基；R.sub.2和R.sub.3，可以相同也可以不同，每个代表具有1至5个碳原子的较低烷基基团，以及制备该衍生物的方法。本发明化合物具有强烈的诱导分化活性和细胞增殖抑制活性，预计可用作抗肿瘤剂、抗风湿剂、治疗牛皮癣的治疗剂和治疗甲状旁腺功能亢进的治疗剂。本发明的方法使得可以高效地生产所需的22-氧合胆钙化醇衍生物，同时减少副产物的产生。
• Synthetic Studies of Vitamin D Analogues. XI. Synthesis and Differentiation-Inducing Activity of 1.ALPHA.,25-Dihydroxy-22-oxavitamin D3 Analogues.
  作者：Noboru KUBODERA、Hiroyoshi WATANABE、Takehiko KAWANISHI、Masahiko MATSUMOTO

  DOI：10.1248/cpb.40.1494

  日期：——

  Six analogues of 1α, 25-dihydroxy-22-oxavitamin D3 (OCT) (2), 26, 27-dimethyl OCT (5), 26, 27-diethyl OCT (6), 24-norOCT (7), 24-homoOCT (8), 24-dihomoOCT (9), and 24-trihomoOCT (10) were synthesized from the 20(S)-alcohol (11) as the common starting material. In the activity inducing differentiation of human myeloid leukemia cells (HL-60) into macrophages, 26, 27-dimethyl OCT (5) and 24-homoOCT (8) showed the highest activities. The binding properties of these analogues to the chick embryonic intestinal 1α, 25-dihydroxyvitamin D3 (1) receptor are also described.

  1α, 25-二羟基-22-奥沙维他命 D3 (OCT) (2)、26, 27-二甲基 OCT (5)、26, 27-二乙基 OCT (6)、24-norOCT (7)、24-homoOCT 的六种类似物(8)、24-dihomoOCT (9) 和 24-trihomoOCT (10) 由 20(S)-醇 (11) 作为共同起始原料合成。在诱导人骨髓性白血病细胞（HL-60）向巨噬细胞分化的活性中，26, 27-二甲基OCT（5）和24-homoOCT（8）表现出最高活性。还描述了这些类似物与鸡胚肠道 1α, 25-二羟基维生素 D3 (1) 受体的结合特性。
• Production and Specificity of Anti-22-oxacalcitriol Antisera.
  作者：Norihiro KOBAYASHI、Tomoko ASANO、Junichi KITAHORI、Kazutake SHIMADA、Noboru KUBODERA、Hiroyoshi WATANABE

  DOI：10.1248/cpb.40.1520

  日期：——

  22-Oxacalcitriol 3-hemiglutarate, a haptenic derivative of 22-oxacalcitriol, was synthesized to obtain a specific antibody for use in radioimmunoassay. Three antisera were elicited in rabbits against the hapten conjugated with bovine serum albumin, and their specificity was examined by cross-reaction study. One of the antisera was found to be satisfactorily specific, and expected to provide a radioimmunoassay useful for the pharmacokinetic study of 22-oxacalcitriol.

  22-oxacalcitriol 3-hemiglutarate 是 22-oxacalcitriol 的一种杂环衍生物，通过合成该杂环衍生物，我们获得了一种可用于放射免疫分析的特异性抗体。针对与牛血清白蛋白共轭的合蛋白，在兔子体内激发了三种抗血清，并通过交叉反应研究检验了它们的特异性。其中一种抗血清的特异性令人满意，有望为 22-氧卡三醇的药代动力学研究提供有用的放射免疫测定。
• Industrial Synthesis of Maxacalcitol, the Antihyperparathyroidism and Antipsoriatic Vitamin D₃ Analogue Exhibiting Low Calcemic Activity
  作者：Hitoshi Shimizu、Kazuki Shimizu、Noboru Kubodera、Tetsuhiro Mikami、Kaname Tsuzaki、Hiroyuki Suwa、Koji Harada、Akira Hiraide、Motoki Shimizu、Kaichiro Koyama、Yoshihide Ichikawa、Daisuke Hirasawa、Yasushi Kito、Mio Kobayashi、Masaharu Kigawa、Masahiro Kato、Toshiro Kozono、Hideki Tanaka、Makoto Tanabe、Masanori Iguchi、Mitsutaka Yoshida

  DOI：10.1021/op049822x

  日期：2005.5.1

  Maxacalcitol, the 22-oxa-derivative of 1 alpha,25-dihydroxyvitamin D-3 and used currently as an antihyperparathyroidism and antipsoriatic drug, has been synthesized in seven chemical steps from 1 alpha-hydroxydehydroepiandrosterone on the basis of our previously developed route. The present synthesis allows the production of the protected form of the penultimate intermediate in 26% overall yield in a kilogram scale reaction employing neither difficult reaction conditions nor chromatographic purification, having overcome all the difficulties involved in the previous route.