1α,2α-epoxy-5,7-cholestadiene-3β-25-diol | 151546-04-2

• 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,2α-epoxy-5,7-cholestadiene-3β-25-diol
• 英文别名: 1α,2α-oxido-cholesta-5,7-dien-3β,25-diol；3β,25-dihydroxy-1α,2α-epoxy-5,7-cholestadiene；3beta,25-Dihydroxy-1alpha,2alpha-epoxy-5,7-cholestadiene；(1S,2R,3R,5S,6R,12R,15R,16R)-15-[(2R)-6-hydroxy-6-methylheptan-2-yl]-2,16-dimethyl-4-oxapentacyclo[9.7.0.02,8.03,5.012,16]octadeca-8,10-dien-6-ol
• CAS: 151546-04-2
• 化学式: C₂₇H₄₂O₃
• 分子量: 414.629
• InChiKey: LWUCYUMEDSBUDH-XDJPBLSNSA-N

物化性质

• 沸点：
  551.5±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  53
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1α,2α-epoxy-5,7-cholestadiene-3β-25-diol 在 盐酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以92%的产率得到2β-chloro-cholesta-5,7-dien-1α,3β,25-triol
  参考文献：
  名称：

  Synthesis and biological activities of 2β-chloro-, 2β-fluoro-, and 2β-methoxy-1α,25-dihydroxyvitamin D3

  摘要：

  Using 1 alpha,2 alpha-oxido-cholesta-5,7-diene-3 beta,25-diol (2) as a starting material, the provitamins of calcitriol with an additional 2 beta-chloro-, 2 beta-flouro, and 2 beta-methoxy-substituent (3,4,5) are obtained by transdiaxial opening of the oxirane ring with nucleophiles. An efficient irradiation process is described and used for the synthesis of the 2 beta-substituted calcitriols NS2, (2 beta-Cl), NS6 (2 beta-F), and NS7 (2 beta-OCH3). The affinity of these three vitamin D-3 derivatives to the vitamin D receptor (VDR) and was determined. These three A-ring derivatives of 1,25(OH)(2)D-3 were further tested for their proliferation-inhibitory and anti-adipogenic activity and gene regulatoric activity in the vitamin D-3-sensitive, murine, mesenchymal cell line C3H10T1/2. The VDR-affinity of the 2 beta-chloro derivative, NS2 (2 beta-Cl), was identical to 1,25(OH)(2)D-3 and its vitamin D binding protein (DBP)-affinity was in the range of 1,25(OH)(2)D-3. NS2 inhibited the proliferation of C3H10T1/2(BMP-4)-cells in the presence of fetal calf serum (FCS) 9 times, and, in the absence of FCs, 111 times lower, as compared with 1,25(OH)(2)D-3. The ID50 dose of adipogenesis-inhibition of NS2 was 13 times higher than the ID50 dose of 1,25(OH)(2)D-3. NS6 (2 beta-F) displayed a slightly higher affinity than 1,25(OH)(2)D-3 to the VDR and the DBP-affinity. The proliferation-inhibitory activity in the presence of FCS was 90 times higher, as compared with 1,25(OH)(2)D-3. NS6 showed an 5 times higher potency to inhibit (pre)adipocyte-differentiation in C3H10T1/2(BMP-4)-cells than 1,35(OH)(2)D-3. NS7 (2 beta-OCH3) showed the lowest VDR-affinity and the highest DBP-affinity of the tested substances, as compared with 1,25(OH)(2)D-3 (11 times lower and 35 times higher respectively). Its proliferation-inhibitory activity in the FCS-free medium was 9 times and in the FCS-containing assay 67 times lower in comparison with 1,25(OH)(2)D-3. A 1250 times higher NS7-dose was needed to reach the anti-adipogenic potency of 1,25(OH)(2)D-3. All tested substances displayed a similar ability to activate a vitamin D responsive element-regulated reporter gene compared to 1,25(OH)(2)D-3 (NS2 and NS6: 1.3 times higher activity; NS7: 1,4 times lower activity). (Steroids 63:633-643, 1998). (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(98)00072-5
• 作为产物：
  描述：

  1α,2α-epoxy-5α,8α-(4-phenyl-3,5-dioxo-1,2,4-triazolidine)-6-cholestene-3β,25-diol 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 xylene 为溶剂， 反应 1.5h， 以89%的产率得到1α,2α-epoxy-5,7-cholestadiene-3β-25-diol
  参考文献：
  名称：

  A Convenient Method for Retro-Cycloaddition of Adducts from Steroidal 5,7-Dienes and 4-Phenyl-1,2,4-triazolidine-3,5-dione and Application to the Syntheses of Biosynthetic Intermediates of Ergosterol.

  摘要：

  在沸腾的二甲苯中使用1, 8-二氮杂双环[5.4.0]十一烯（DBU）被发现是一种便捷的方法，用于4-苯基-1, 2, 4-三氮唑-3, 5-二酮（PTAD）与固醇5, 7-二烯加合物的逆环加成。这一过程被应用于合成ergosta-5, 7, 24(28)-三烯-3β-醇和ergosta-5, 7, 22, 24(28)-四烯-3β-醇。

  DOI：

  10.1248/cpb.46.1454

文献信息

• Synthetic Studies of Vitamin D Analogs. XXIV. Synthesis of Active Vitamin D3 Analogs Substituted at the 2.BETA.-Position and Their Preventive Effects on Bone Mineral Loss in Ovariectomized Rats.
  作者：Yoshiyuki ONO、Hiroyoshi WATANABE、Ayako SHIRAISHI、Satoshi TAKEDA、Yoshinobu HIGUCHI、Katsuhiko SATO、Naoko TSUGAWA、Toshio OKANO、Tadashi KOBAYASHI、Noboru KUBODERA

  DOI：10.1248/cpb.45.1626

  日期：——

  Analogs related to 1α, 25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)(4), oxa-type and carba-type analogs of vitamin D3 bearing substituents at the 2β-position of 1α, 25-dihydroxyvitamin D3 (1), were synthesized from the α-epoxides (6 and 13). Three analogs, ED-71 (4) and two carba-type analogs (16 and 26), showed potent preventive effects on bone mineral loss in pre-osteoporosis model rats. ED-71 (4) was concluded to be an optimized analog and a promising candidate for the treatment of osteoporosis.

  由α-环氧化物（6 和 13）合成了与 1α，25-二羟基-2β-(3-羟基丙氧基)维生素 D3 (ED-71)(4) 有关的类似物，以及在 1α，25-二羟基维生素 D3 (1) 的 2β 位上带有取代基的维生素 D3 的羰基型和羧基型类似物。三种类似物，即 ED-71 (4) 和两种卡巴型类似物（16 和 26），对骨质疏松症前期模型大鼠的骨矿物质流失具有有效的预防作用。ED-71（4）被认为是一种优化的类似物，有望成为治疗骨质疏松症的候选药物。
• Process for producing 1,2,3-trioxysteroid derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05874598A1

  公开（公告）日：1999-02-23

  A process for the production of a compound of formula (II), which comprises reacting an epoxy compound of formula (I) with an alcohol, wherein the reaction is carried out under a basic condition. ##STR1## R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are as defined in the specification. The compounds are useful intermediates for the production of vitamin D.sub.3 derivatives.

  一种生产化合物（II）的过程，包括将式（I）的环氧化合物与醇反应，在碱性条件下进行反应。其中，##STR1## R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6的定义如规范中所述。这些化合物是生产维生素D.sub.3衍生物的有用中间体。
• Synthetic Studies of Vitamin D Analogues. XIV. Synthesis and Calcium Regulating Activity of Vitamin D3 Analogues Bearing a Hydroxyalkoxy Group at the 2.BETA.-Position.
  作者：Katsuhito MIYAMOTO、Eigoro MURAYAMA、Kiyoshige OCHI、Hiroyoshi WATANABE、Noboru KUBODERA

  DOI：10.1248/cpb.41.1111

  日期：——

  Four vitamin D3 analogues (7a, 7b, 7c and 7d) bearing a hydroxyalkoxy group at the 2β-position were synthesized from the α-epoxide (5). The C-3 analogue (7b) showed the highest potency for elevating plasma calcium levels in rats. Furthermore, the 25-hydroxylated C-3 analogue (ED-71) (3), prepared from the 25-hydroxylated α-epoxide (9), significantly increased plasma calcium to levels much higher than those in rats administered 1α, 25-(OH)2-D3 (1).

  从 α-环氧化物 (5) 合成了 2β 位带有羟基烷氧基的四种维生素 D3 类似物 (7a、7b、7c 和 7d)。 C-3 类似物 (7b) 显示出提高大鼠血浆钙水平的最高效力。此外，由 25-羟基化 α-环氧化物 (9) 制备的 25-羟基化 C-3 类似物 (ED-71) (3) 显着增加血浆钙水平，其水平远高于施用 1α, 25-( OH)2-D3 (1)。
• Vitamin D derivative with substituent at the 2.beta.-position
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05877168A1

  公开（公告）日：1999-03-02

  A 1.alpha.-hydroxy-vitamin D derivative represented by formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom or a hydroxyl group; and R.sub.2 represents a straight-chain or branched lower alkyl, lower alkenyl or lower alkynyl group, which is substituted with a hydroxyl group, a halogen atom, a cyano group, a lower alkoxy group, an amino group or an acylamino group, is disclosed. The compound exhibits calcium metabolism regulating activity and differentiation stimulating activity on tumor cells, etc. and is useful as a treating agent for diseases caused by abnormal calcium metabolism, such as osteoporosis and osteomalacia, or as an antitumor agent.

  一种由公式（I）表示的α-羟基维生素D衍生物：##STR1##其中R.sub.1代表氢原子或羟基基团；R.sub.2代表直链或支链低级烷基，低级烯基或低级炔基，其被羟基基团，卤素原子，氰基，低级烷氧基，氨基或酰胺基取代，该化合物表现出调节钙代谢和刺激肿瘤细胞分化等活性，并可用作治疗因异常钙代谢引起的疾病，如骨质疏松和软骨病，或作为抗肿瘤剂。
• PROCESS FOR PRODUCING PROVITAMIN D COMPOUND
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0671411A1

  公开（公告）日：1995-09-13

  A process for producing a compound represented by general formula (II) by the reaction of an epoxy compound represented by general formula (I) with an alcohol under a basic condition, wherein R₁ represents hydrogen or a protective group; R₂ represents hydrogen or hydroxy; R₃, R₄, R₅ and R₆ represent such groups that a pair of R₃ and R₄ and a pair of R₅ and R₆ form each a double bond, or a pair of R₄ and R₅ forms a double bond while R₃ and R₆ are bonded to a dienophile capable of protecting conjugated double bonds; and R₇ represents lower alkyl, cycloalkyl or optionally protected lower hydroxyalkyl. This process is one for synthesizing an intermediate of a vitamin D derivative in an imptroved yield without the necessity for complicated procedure of protection and is also suited for mass production.

  一种通过通式(I)代表的环氧化合物与醇在碱性条件下反应制得通式(II)代表的化合物的工艺，其中R₁代表氢或保护基；R₂代表氢或羟基；R₃、R₄、R₅ 和 R₆ 代表这样的基团，即一对 R₃ 和 R₄ 以及一对 R₅ 和 R₆ 各自形成一个双键、或一对 R₄ 和 R₅ 形成双键，而 R₃ 和 R₆ 与能够保护共轭双键的亲二烯键结合；和 R₇ 代表低级烷基、环烷基或可选保护的低级羟基烷基。这种工艺可以合成维生素 D 衍生物的中间体，产量高，无需复杂的保护程序，也适合大规模生产。