trimethyl (Z,3R)-3-hydroxy-1-methylbut-1-ene-1,2,4-tricarboxylate | 130714-58-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: trimethyl (Z,3R)-3-hydroxy-1-methylbut-1-ene-1,2,4-tricarboxylate
• CAS: 130714-58-8
• 化学式: C₁₁H₁₆O₇
• 分子量: 260.244
• InChiKey: ZOGCQMNUKAVHCT-WRDFDADTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  trimethyl (Z,3R)-3-hydroxy-1-methylbut-1-ene-1,2,4-tricarboxylate 、 4-溴苯甲酰氯 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以50%的产率得到trimethyl (Z,3R)-3-(4-bromobenzoyl)oxy-1-methylbut-1-ene-1,2,4-tricarboxylate
  参考文献：
  名称：

  Ubukata, Makoto; Cheng, Xing-Chun; Isobe, Minoru, Journal of the Chemical Society. Perkin transactions I, 1993, # 5, p. 617 - 624

  摘要：

  DOI：
• 作为产物：
  描述：

  Ethyl (2Z,4R)-4-<oxy>-5-formyl-2-methyl-3-<(1,1-dimethylethoxy)carbonyl>-2-pentenoate 在 palladium dichloride 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium chlorite 、 sodium periodate 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 氢氟酸 、 水 、 氧气 、 三乙基硅基三氟甲磺酸酯 、 四氯化钛 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 、 三氟乙酸酐 、 copper(l) chloride 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 34.84h， 生成 trimethyl (Z,3R)-3-hydroxy-1-methylbut-1-ene-1,2,4-tricarboxylate
  参考文献：
  名称：

  Total Synthesis of Tautomycin

  摘要：

  A convergent stereocontrolled synthesis of the antifungal antibiotic tautomycin, a potent protein phosphatases inhibitor, has been achieved first via key aldol coupling of two large subunits, a right-hand C-1-C-21 ketone and a left-hand aldehyde (left from C-22). The C-1-C-10 segment was synthesized through a remote stereochemical control process using a spiroketal template. After joining with the C-11-C-18 segment, the spiroketal moiety was selectively constructed. Then the right-hand C-1-C-21 ketone was synthesized via Roush asymmetric crotylboration. The left-hand aldehyde was prepared from a C-21-C-26 Segment and a dialkylmaleic anhydride segment. Completely stereoselective assemblage of the two subunits, the right-hand and the left-hand, was achieved by employing the Mukaiyama aldol reaction. Further functional group manipulations including desilylation, oxidation at C-2, and deprotection of tert-butyl ester with concomitant anhydride formation provided tautomycin which was identical with the natural product. As a preliminary study, derivatizations and degradation of the natural product were also examined to support the total synthesis.

  DOI：

  10.1021/jo00121a026

文献信息

• Structure-Activity Relationship within a Series of Degradation Products of Tautomycin
  作者：Uichi Nishiyama、Makoto Ubukata、Junji Magae、Takao Kataoka、Ferenc Erdödi、David J. Hartshorne、Kiyoshi Isono、Kazuo Nagai、Hiroyuki Osada

  DOI：10.1271/bbb.60.103

  日期：1996.1

  Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the

  互变霉素是一种蛋白质丝氨酸/苏氨酸磷酸酶抑制剂，被化学降解，并研究了五种衍生物的生物活性。它们均未对1型和2A型蛋白磷酸酶的活性产生任何抑制作用。但是，一种名为TM2a的衍生物诱导了人类髓样白血病K562细胞的显着形态变化（气泡形成）。TM2b，TM2的三甲酯，不引起起泡。因此，马来酸酐结构在生物活性中起重要作用。TM2a对K562细胞的生物学特性类似于佛波酯而不是互变霉素的生物学特性。佛波酯诱导的气泡形成被蛋白激酶的非特异性抑制剂星形孢菌素和蛋白激酶C（PKC）的抑制剂H-7废除了，但是TM2a诱导的气泡形成只能由星形孢菌素消除。两种蛋白质暴露于TM2a后，观察到磷酸化增强。这表明该作用不是由于对蛋白磷酸酶1或2A的任何抑制，而是由于未识别的激酶（可能是PKC家族）的激活，或由于1型或2A型以外的蛋白磷酸酶的抑制。
• Synthetic studies on tautomycin
  作者：Atsushi Naganawa、Yoshiyasu Ichikawa、Minoru Isobe

  DOI：10.1016/s0040-4020(01)85365-5

  日期：1994.1

  The 2,3-disubstituted maleic anhydride segment of tautomycin has been synthesized in optically active form. Oxidation of 3,4-disubsrituted furan employing singlet oxygen completes the construction of the maleic anhydride moiety. Esterification of the maleic anhydride segment without protecting anhydride moiety resulted in the successful coupling reaction with fragment derived from tautomycin.
• Oikawa, Hideaki; Oikawa, Masato; Ichihara, Akitami, Bioscience, Biotechnology and Biochemistry, 1994, vol. 58, # 10, p. 1933 - 1935
  作者：Oikawa, Hideaki、Oikawa, Masato、Ichihara, Akitami、Ubukata, Makoto、Isono, Kiyoshi

  DOI：——

  日期：——
• Total Synthesis of Tautomycin
  作者：Masato Oikawa、Tohru Ueno、Hideaki Oikawa、Akitami Ichihara

  DOI：10.1021/jo00121a026

  日期：1995.8

  A convergent stereocontrolled synthesis of the antifungal antibiotic tautomycin, a potent protein phosphatases inhibitor, has been achieved first via key aldol coupling of two large subunits, a right-hand C-1-C-21 ketone and a left-hand aldehyde (left from C-22). The C-1-C-10 segment was synthesized through a remote stereochemical control process using a spiroketal template. After joining with the C-11-C-18 segment, the spiroketal moiety was selectively constructed. Then the right-hand C-1-C-21 ketone was synthesized via Roush asymmetric crotylboration. The left-hand aldehyde was prepared from a C-21-C-26 Segment and a dialkylmaleic anhydride segment. Completely stereoselective assemblage of the two subunits, the right-hand and the left-hand, was achieved by employing the Mukaiyama aldol reaction. Further functional group manipulations including desilylation, oxidation at C-2, and deprotection of tert-butyl ester with concomitant anhydride formation provided tautomycin which was identical with the natural product. As a preliminary study, derivatizations and degradation of the natural product were also examined to support the total synthesis.
• Ubukata, Makoto; Cheng, Xing-Chun; Isobe, Minoru, Journal of the Chemical Society. Perkin transactions I, 1993, # 5, p. 617 - 624
  作者：Ubukata, Makoto、Cheng, Xing-Chun、Isobe, Minoru、Isono, Kiyoshi

  DOI：——

  日期：——