5-bromo-2-methyl-2-pentanol, MOM ether

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-bromo-2-methyl-2-pentanol, MOM ether
• 英文别名: 4-(methoxymethoxy)-4-methylpentyl bromide；1-Bromo-4-(methoxymethoxy)-4-methylpentane
• 化学式: C₈H₁₇BrO₂
• 分子量: 225.126
• InChiKey: KLPVFQMJFZCAKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2S,6S,7Z,8S,9R)-2-[(tert-butyldimethylsilyl)oxy]-8,9-epoxy-7-ethylidene-6-methylbicyclo[4.3.0]nonane 、 5-bromo-2-methyl-2-pentanol, MOM ether 在 magnesium 、 copper(l) cyanide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 21.0h， 以67%的产率得到(1S,5S,6S,7S)-5-[(tert-butyldimethylsilyl)oxy]-9-[(R)-6-(methoxymethoxy)-6-methylheptan-2-yl]-1-methylbicyclo[4.3.0]non-8-en-7-ol
  参考文献：
  名称：

  New C15-Substituted Active Vitamin D₃

  摘要：

  C15-Substituted 1 alpha,25-dihydroxyvitamin D-3 analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 angstrom shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.

  DOI：

  10.1021/ol200828s
• 作为产物：
  描述：

  二甲醇缩甲醛 、 5-bromo-2-methylpentan-2-ol 在 phosphorus pentoxide 作用下， 以 氯仿 为溶剂， 反应 1.83h， 以69%的产率得到5-bromo-2-methyl-2-pentanol, MOM ether
  参考文献：
  名称：

  Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

  摘要：

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.

  DOI：

  10.1021/jm00041a013

文献信息

• New C15-Substituted Active Vitamin D₃
  作者：Kanako Shindo、Go Kumagai、Masashi Takano、Daisuke Sawada、Nozomi Saito、Hiroshi Saito、Shinji Kakuda、Ken-ichiro Takagi、Eiji Ochiai、Kyohei Horie、Midori Takimoto-Kamimura、Seiichi Ishizuka、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1021/ol200828s

  日期：2011.6.3

  C15-Substituted 1 alpha,25-dihydroxyvitamin D-3 analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 angstrom shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.
• Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription
  作者：Scott D. Larsen、Charles H. Spilman、Yoshi Yagi、Dac M. Dinh、Karen L. Hart、Gerard F. Hess

  DOI：10.1021/jm00041a013

  日期：1994.7

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.