(Z)-3,4-bis(benzyloxy)-5-(2-hydroxyethylidene)furan-2(5H)-one | 185675-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: (Z)-3,4-bis(benzyloxy)-5-(2-hydroxyethylidene)furan-2(5H)-one
• 英文别名: (Z)-3,4-dibenzyloxy-5-(2-hydroxyethylidene)-5H-2-one；Z-2,3-di-O-benzyl-4,5-didehydro-L-ascorbic acid；(5Z)-5-(2-hydroxyethylidene)-3,4-bis(phenylmethoxy)furan-2-one
• CAS: 185675-57-4
• 化学式: C₂₀H₁₈O₅
• 分子量: 338.36
• InChiKey: WOIRSMPSDUXFPK-BOPFTXTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-3,4-bis(benzyloxy)-5-(2-hydroxyethylidene)furan-2(5H)-one 在 吡啶 、 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 苯甲酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 1.0h， 生成 (Z)-2,3-O,O-dibenzyl-6-(4-butyl-1,2,3-triazole-1-yl)-4,5-didehydro-5,6-dideoxy-L-ascorbic acid
  参考文献：
  名称：

  γ-（三唑基亚乙基）丁烯内酯和多官能吡咯烷酮的合成及抗癌活性

  摘要：

  一系列新颖的γ-（三唑基亚乙基）丁烯羟酸内酯的（4 - 23）从可商购的制备升以良好的收率抗坏血酸。与乙醇氨反应这些丁烯羟酸内酯/胺导致形成相应的5-羟基pyrrolinones（的24 - 33）。用对甲苯磺酸脱水后，将其中的两个吡咯烷酮转化为γ-（三唑基亚乙基）吡咯烷酮（34、35）。在所有新测试的体外抗癌活性杂合分子中，化合物24、25、26、27、28、30和32对MCF-7，MDA-MB-231，PC-3或U-937细胞显示出显着活性。特别是化合物25（IC 50  = 11.3μM）对乳腺癌细胞表现出最强的活性，初步研究表明，该化合物的效力归因于ROS的产生，随后p38的活化，导致凋亡和癌细胞的抑制。

  DOI：

  10.1016/j.ejmech.2014.05.042
• 作为产物：
  描述：

  (2R)-3,4-dibenzyloxy-2-[(1S)-1,2-dihydroxyethyl]-2H-furan-5-one 在 吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (Z)-3,4-bis(benzyloxy)-5-(2-hydroxyethylidene)furan-2(5H)-one
  参考文献：
  名称：

  Synthesis, structural studies, and cytostatic evaluation of 5,6-di-O-modified l-ascorbic acid derivatives

  摘要：

  The 5,6-di-O-tosylated derivative Of (L)-ascorbic acid was synthesized by selective protection and deprotection of 2,3- and 5.6-dihydroxy functional groups involving 5,6-ditosylation in the final step, while the novel 6-acetoxy, 6-hydroxy, and 6-chloro derivatives of 4,5-didehydro-L-ascorbic acid were obtained by reaction of ditosylated compound with nucleophilic reagents. The analysis Of (3)J(H-4-H-5) homonuclear coupling constants shows that all L-ascorbic acid derivatives except for epoxy and 4,5-didehydro compounds exist in high population as gauche conformers across C-4-C-5 bonds, while (3)J(C-3-H-5) heteronuclear coupling constants in 4,5-didehydro derivatives indicate cis geometry along C-4-C-5 double bond. The X-ray crystal structure analysis of 2,3-di-O-benzyl-5,6-epoxy- and 5.6-isopropylidene-L-ascorbic acid shows that the oxygen atoms attached at positions 2 and 3 of the lactone ring are disposed in a synperiplanar fashion. Besides that, the dioxolane ring adopts half-chair conformation. The molecules of epoxy derivative are joined into infinite chains by one weak hydrogen bond of C-(HO)-O-center dot center dot center dot type. Two O-(HO)-O-center dot center dot center dot, and C-(HO)-O-center dot center dot center dot hydrogen bonds link the molecules of 5,6-di-O-isopropylidene compound into two-dimensional network. 6-Chloro derivative of 2,3-di-O-benzyl-L-ascorbic acid showed the best cytostatic effects against all tested malignant tumor cells (IC50: similar to 18 mu M) (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2005.12.010

文献信息

• Organoalane-mediated isomerization of ascorbic and isoascorbic acid derivatives
  作者：Josef Schachtner、Hans-Dietrich Stachel

  DOI：10.1016/0957-4166(96)00427-2

  日期：1996.11

  removal of the protecting groups is effected by hydrogenolysis of the benzylidene acetals ent-10 and ent-11a. This reaction leads to d-ascorbic acid ent-1a or l-isoascorbic acid ent-1b, respectively. Furthermore, the four acetonides 2 were converted by ozonolysis, transesterification and finally catalytic hydrogenation to the threonic and erythronic acid ketals 9.

  当用三异丁基铝处理时，l-抗坏血酸2a和d-异抗坏血酸2b的衍生物部分发生差向异构化，生成l-异抗坏血酸ent - 2b，ent -10b或d-抗坏血酸ent - 2a ，ent -11a分别。保护基的完全除去是通过对亚甲基缩醛ent -10和ent- 11a进行氢解来实现的。该反应导致d抗坏血酸ENT -1a或1-异抗坏血酸ENT分别-1b。此外，四种丙酮化物2被臭氧分解，酯交换，最后催化氢化转化为苏糖醛和赤藓酸缩酮9。
• l-Ascorbic acid in organic synthesis: a facile synthesis of 4-(butenolide-5-methylidenyl)-1,4-dihydropyridines
  作者：Surendra S. Bisht、Namrata Dwivedi、Rama P. Tripathi

  DOI：10.1016/j.tetlet.2006.12.067

  日期：2007.2

  efficient synthesis of 4-(butenolide-5-methylidenyl)-1,4-dihydropyridines has been achieved via a three-component reaction of β-keto esters or ketones, ammonium acetate and vinylic aldehydes from ascorbic acid in the presence of tetrabutylammonium hydrogen sulfate in ethylene glycol.

  在四丁基铵氢存在下，由抗坏血酸通过β-酮酸酯或酮，乙酸铵和乙烯基醛的三组分反应，实现了4-（丁烯内酯-5-亚甲基）-1,4-二氢吡啶的有效合成。乙二醇中的硫酸盐。
• l-Ascorbic acid in organic synthesis: DBU-catalysed one-pot synthesis of tetramic acid derivatives from 5,6-O-isopropylidene ascorbic acid
  作者：Biswajit K. Singh、Shyam S. Verma、Namrata Dwivedi、Rama P. Tripathi

  DOI：10.1016/j.tetlet.2006.01.098

  日期：2006.3

  Reaction of 5,6-O-isopropylidene-2,3-bis-O-alkyl ascorbic acid with different amines in the presence of DBU at ambient temperature resulted in the formation of 3,4-bis-O-alkyl-l-alkyl-5-(2-hydroxy ethyl)-5-hydroxy-1,5-dihydropyrrol-2-ones in moderate yields. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and anticancer activity of γ-(triazolyl ethylidene)butenolides and polyfunctional pyrrolinones
  作者：N. Devender、K.K.G. Ramakrishna、Hamidullah、Sanjeev K. Shukla、Rituraj Konwar、Rama P. Tripathi

  DOI：10.1016/j.ejmech.2014.05.042

  日期：2014.7

  ethylidene)butenolides (4–23) were prepared from commercially available l-ascorbic acid in good yields. These butenolides on reaction with ethanolic ammonia/amines led to formation of respective 5-hydroxy pyrrolinones (24–33). The two of these pyrrolinones on dehydration with p-toluenesulfonic acid, were transformed into γ-(triazolyl ethylidene)pyrrolinones (34, 35). Among all the newly synthesized hybrid

  一系列新颖的γ-（三唑基亚乙基）丁烯羟酸内酯的（4 - 23）从可商购的制备升以良好的收率抗坏血酸。与乙醇氨反应这些丁烯羟酸内酯/胺导致形成相应的5-羟基pyrrolinones（的24 - 33）。用对甲苯磺酸脱水后，将其中的两个吡咯烷酮转化为γ-（三唑基亚乙基）吡咯烷酮（34、35）。在所有新测试的体外抗癌活性杂合分子中，化合物24、25、26、27、28、30和32对MCF-7，MDA-MB-231，PC-3或U-937细胞显示出显着活性。特别是化合物25（IC 50  = 11.3μM）对乳腺癌细胞表现出最强的活性，初步研究表明，该化合物的效力归因于ROS的产生，随后p38的活化，导致凋亡和癌细胞的抑制。
• Synthesis, structural studies, and cytostatic evaluation of 5,6-di-O-modified l-ascorbic acid derivatives
  作者：Tatjana Gazivoda、Karlo Wittine、Iva Lovrić、Damjan Makuc、Janez Plavec、Mario Cetina、Draginja Mrvoš-Sermek、Lidija Šuman、Marijeta Kralj、Krešimir Pavelić、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1016/j.carres.2005.12.010

  日期：2006.3

  The 5,6-di-O-tosylated derivative Of (L)-ascorbic acid was synthesized by selective protection and deprotection of 2,3- and 5.6-dihydroxy functional groups involving 5,6-ditosylation in the final step, while the novel 6-acetoxy, 6-hydroxy, and 6-chloro derivatives of 4,5-didehydro-L-ascorbic acid were obtained by reaction of ditosylated compound with nucleophilic reagents. The analysis Of (3)J(H-4-H-5) homonuclear coupling constants shows that all L-ascorbic acid derivatives except for epoxy and 4,5-didehydro compounds exist in high population as gauche conformers across C-4-C-5 bonds, while (3)J(C-3-H-5) heteronuclear coupling constants in 4,5-didehydro derivatives indicate cis geometry along C-4-C-5 double bond. The X-ray crystal structure analysis of 2,3-di-O-benzyl-5,6-epoxy- and 5.6-isopropylidene-L-ascorbic acid shows that the oxygen atoms attached at positions 2 and 3 of the lactone ring are disposed in a synperiplanar fashion. Besides that, the dioxolane ring adopts half-chair conformation. The molecules of epoxy derivative are joined into infinite chains by one weak hydrogen bond of C-(HO)-O-center dot center dot center dot type. Two O-(HO)-O-center dot center dot center dot, and C-(HO)-O-center dot center dot center dot hydrogen bonds link the molecules of 5,6-di-O-isopropylidene compound into two-dimensional network. 6-Chloro derivative of 2,3-di-O-benzyl-L-ascorbic acid showed the best cytostatic effects against all tested malignant tumor cells (IC50: similar to 18 mu M) (c) 2006 Elsevier Ltd. All rights reserved.