fumaric acid bis<2-(trimethylsilyl)ethyl>ester | 75940-35-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: fumaric acid bis<2-(trimethylsilyl)ethyl>ester
• 英文别名: bis<2-(trimethylsilyl)ethyl> fumarate；di-β-trimethylsilylethyl fumarate；bis[2-(trimethylsilyl)ethyl] fumarate；bis(2-trimethylsilylethyl) (E)-but-2-enedioate
• CAS: 75940-35-1
• 化学式: C₁₄H₂₈O₄Si₂
• 分子量: 316.545
• InChiKey: IZJKRSPUGQCARC-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  fumaric acid bis<2-(trimethylsilyl)ethyl>ester 在 四氧化锇 、 对甲苯磺酸 十二/十四烷基二甲基氧化胺 、 zinc(II) iodide 作用下， 以 丙酮 、 叔丁醇 为溶剂， 反应 52.0h， 生成 bis<2-(trimethylsilyl)ethyl> (2-exo,3-endo,5-exo,6-exo)-5,6-dihydroxy-7-oxabicyclo<2.2.1>heptane-2,3-dicarboxylate acetonide
  参考文献：
  名称：

  The stereocontrolled synthesis of phthalic acid 4,5-cis-dihydrodiol. An unambiguous structural assignment of the bacterial metabolite of phthalic acid

  摘要：

  The stereocontrolled synthesis of the extremely labile phthalic acid 4,5-cis-dihydrodiol (1) has been achieved in a highly efficient manner in seven steps from bis[2-(trimethylsilyl)ethyl] fumarate (2). The Diels-Alder adduct 3 of the fumarate with furan has been converted into first exo-cis-diol 4 and then its acetonide 5. Treatment of acetonide 5 with lithium hexamethyldisilazide results in the regioselective formation of olefinic alcohol 6. Following the introduction of the second double bond into the cyclohexene ring system, the highly sensitive deprotection of the acetonide group of dihydrodiol diester acetonide 7 can be effected under iodine catalysis. The hydrolysis of the 2-(trimethylsilyl)ethyl ester group has been achieved by treatment with tetra(n-butyl)-ammonium fluoride in THF. This synthesis constitutes an unambiguous assignment of the structure and stereochemistry of the microbial metabolite of phthalic acid.

  DOI：

  10.1021/jo00040a023
• 作为产物：
  描述：

  反丁烯二酰氯 、 2-(三甲硅基)乙醇 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以81%的产率得到fumaric acid bis<2-(trimethylsilyl)ethyl>ester
  参考文献：
  名称：

  The stereocontrolled synthesis of phthalic acid 4,5-cis-dihydrodiol. An unambiguous structural assignment of the bacterial metabolite of phthalic acid

  摘要：

  The stereocontrolled synthesis of the extremely labile phthalic acid 4,5-cis-dihydrodiol (1) has been achieved in a highly efficient manner in seven steps from bis[2-(trimethylsilyl)ethyl] fumarate (2). The Diels-Alder adduct 3 of the fumarate with furan has been converted into first exo-cis-diol 4 and then its acetonide 5. Treatment of acetonide 5 with lithium hexamethyldisilazide results in the regioselective formation of olefinic alcohol 6. Following the introduction of the second double bond into the cyclohexene ring system, the highly sensitive deprotection of the acetonide group of dihydrodiol diester acetonide 7 can be effected under iodine catalysis. The hydrolysis of the 2-(trimethylsilyl)ethyl ester group has been achieved by treatment with tetra(n-butyl)-ammonium fluoride in THF. This synthesis constitutes an unambiguous assignment of the structure and stereochemistry of the microbial metabolite of phthalic acid.

  DOI：

  10.1021/jo00040a023

文献信息

• Discovery of the Hemifumarate and (α-<scp>l</scp>-Alanyloxy)methyl Ether as Prodrugs of an Antirheumatic Oxindole:  Prodrugs for the Enolic OH Group
  作者：Ralph P. Robinson、Lawrence A. Reiter、Wayne E. Barth、Anthony M. Campeta、Kelvin Cooper、Brian J. Cronin、Rosalina Destito、Kathleen M. Donahue、Fred C. Falkner、Eugene F. Fiese、Diane L. Johnson、Alexander V. Kuperman、Theodore E. Liston、Deborah Malloy、John J. Martin、David Y. Mitchell、Frank W. Rusek、Sheri L. Shamblin、Charles F. Wright

  DOI：10.1021/jm950575k

  日期：1996.1.1

  acceptable bioavailabilities of 1 across species (rats, dogs, and monkeys) followed the inclusion of ionizable functionality within the promoiety to compensate for masking the polar enolic OH group of the free drug. However, the introduction of ionizable functionality was often associated with decreased stability, as demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and alpha-amino ester derivatives

  制备了抗风湿性羟吲哚1的醚，酯和碳酸酯衍生物，并将其筛选为1的潜在前药。这一工作导致发现了1的（α-L-丙氨氧基）-甲基醚和半富马酸酯衍生物，可以有效地递送药物。进入试验动物的循环中，在固态下是稳定的，并且在确保胃稳定所需的低pH值的溶液中具有良好的稳定性。成功实现了跨物种（大鼠，狗和猴子）1的可接受生物利用度，其原因是在促销品中加入了可离子化的功能，以补偿掩盖游离药物的极性烯醇式OH基团。但是，如半琥珀酸酯，半己二酸酯，半豆酸酯，和无法分离的1的α-氨基酯衍生物。一个明显的例外是1的半富马酸酯衍生物，它在中性pH下不仅可分离，而且实际上比不可电离的酯类似物更稳定。半富马酸盐的溶液和固态稳定性，以及其作为1的前药的活性表明，半富马酸盐被认为是半琥珀酸酯作为醇的前药衍生物的替代物，特别是在溶液状态稳定性是一个问题的情况下。
• MENARD, M.;MARTEL, A.
  作者：MENARD, M.、MARTEL, A.

  DOI：——

  日期：——
• The stereocontrolled synthesis of phthalic acid 4,5-cis-dihydrodiol. An unambiguous structural assignment of the bacterial metabolite of phthalic acid
  作者：Wu Yang、Masato Koreeda

  DOI：10.1021/jo00040a023

  日期：1992.7

  The stereocontrolled synthesis of the extremely labile phthalic acid 4,5-cis-dihydrodiol (1) has been achieved in a highly efficient manner in seven steps from bis[2-(trimethylsilyl)ethyl] fumarate (2). The Diels-Alder adduct 3 of the fumarate with furan has been converted into first exo-cis-diol 4 and then its acetonide 5. Treatment of acetonide 5 with lithium hexamethyldisilazide results in the regioselective formation of olefinic alcohol 6. Following the introduction of the second double bond into the cyclohexene ring system, the highly sensitive deprotection of the acetonide group of dihydrodiol diester acetonide 7 can be effected under iodine catalysis. The hydrolysis of the 2-(trimethylsilyl)ethyl ester group has been achieved by treatment with tetra(n-butyl)-ammonium fluoride in THF. This synthesis constitutes an unambiguous assignment of the structure and stereochemistry of the microbial metabolite of phthalic acid.