(5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-phenylsulfonyl-22,23-dinor-9,10-secochola-5,7,10(19)-triene | 223538-02-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-phenylsulfonyl-22,23-dinor-9,10-secochola-5,7,10(19)-triene
• CAS: 223538-02-1
• 化学式: C₄₀H₆₆O₄SSi₂
• 分子量: 699.199
• InChiKey: KGUUDUHOLNRKCW-MIDJAYLLSA-N

物化性质

• 沸点：
  687.5±55.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-phenylsulfonyl-22,23-dinor-9,10-secochola-5,7,10(19)-triene 在 disodium hydrogenphosphate 、 sodium amalgam 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 4.75h， 生成 (24E)-(1S)-24-dehydro-24a-homo-26,27-di-n-propyl-1,25-dihydroxyergocalciferol
  参考文献：
  名称：

  Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D2

  摘要：

  A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D-2 and D-3. The analogs were obtained by the Julia olefination of C-22-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D-2 with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00038-7
• 作为产物：
  描述：

  (7E)-(1S,3R)-4'-phenyl-6,9-[1',2']epi[1',2',4']triazolo-1,3-bis[(t-butyldimethyl-silyl)oxy]-22,23-dinor-9,10-secochola-5(10),7-dien-24-ol-3',5'-dion 在 4-二甲氨基吡啶 、 氢氧化钾 、 lithium carbonate 、 三乙胺 、 lithium bromide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.83h， 生成 (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-phenylsulfonyl-22,23-dinor-9,10-secochola-5,7,10(19)-triene
  参考文献：
  名称：

  Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D2

  摘要：

  A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D-2 and D-3. The analogs were obtained by the Julia olefination of C-22-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D-2 with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00038-7

文献信息

• [EN] PROCESS FOR THE PREPARATION OF CALCIPOTRIOL<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE CALCIPOTRIOL
  申请人：INST FARMACEUTYCZNY

  公开号：WO2009008754A2

  公开（公告）日：2009-01-15

  Process comprising the step of reacting a C-22 phenylsulphonyl derivative of cholecalciferol of Formula (2), wherein R1 and R2 are the same or different and represent hydroxyl protecting groups, with a silyl derivative of alfa-hydroxy aldehyde of Formula (3), wherein R3 represents silyl group of formula Si(R4) (R5)(R6), where R4-R6 are the same or different and represent C1-6 alkyl or phenyl groups, in the presence of a strong organic base in aprotic solvent, followed by a reductive desulfonation of the diastereomeric mixture of alfa- hydroxysulfones with sodium amalgam, removing the hydroxyl protecting groups, and purification, leads to calcipotriol containing less than 0,3% of (22Z)-isomer and free of mercury traces.

  该过程包括以下步骤：在无极性溶剂中，在强有机碱的存在下，将式（2）中R1和R2相同或不同且代表羟基保护基的C-22苯磺酰基维生素D衍生物与式（3）中R3代表公式Si（R4）（R5）（R6）的硅基衍生物反应，其中R4-R6相同或不同且代表C1-6烷基或苯基，随后通过钠汞齐还原去除α-羟基磺酮的对映体混合物，去除羟基保护基并纯化，得到含少于0.3％（22Z）-异构体并且不含汞痕迹的钙醇三醇。
• METHOD OF PREPARATION OF CHOLECALCIFEROL DERIVATIVES AND NEW INTERMEDIATE COMPOUNDS
  申请人：INSTYTUT FARMACEUTYCZNY

  公开号：EP1047671B1

  公开（公告）日：2003-12-10