methyl N-[β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]glycine pentafluorophenyl ester | 404002-11-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl N-[β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]glycine pentafluorophenyl ester
• 英文别名: methyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[2-nitro-4-[[2-oxo-2-(2,3,4,5,6-pentafluorophenoxy)ethyl]carbamoyloxymethyl]phenoxy]oxane-2-carboxylate
• CAS: 404002-11-5
• 化学式: C₂₃H₁₉F₅N₂O₁₃
• 分子量: 626.401
• InChiKey: AUQMYUAWIJKXGL-QSUZLTIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  216
• 氢给体数：
  4
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  methyl N-[β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]glycine pentafluorophenyl ester 在 disodium hydrogenphosphate 、 pig liver esterase 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-[β-D-(glucopyranuronic acid)-3-nitrobenzyloxycarbonyl]glycyl-L-phenylalanyl-L-leucine
  参考文献：
  名称：

  Synthesis and Biological Activity of the Prodrug of Class I Major Histocompatibility Peptide GILGFVFTL Activated by β-Glucuronidase

  摘要：

  The first synthesis of a prodrug of HLA-A.2.1 associated antigenic influenza peptide 2a was accomplished. Two methods for synthesis of prodrugs of antigenic peptides activated by beta-glucuronidase and comprising a self-immolative 3-nitrobenzyloxycarbonyl moiety were investigated. Reaction of P-glucuronic acid glycoside of 4-hydroxy-3-nitrobenzyl alcohol (3) with N,N'-disuccinimidyl carbonate (DSC) followed by conjugation with AlaOMe, Gly, Thr, Phe-Leu, and Leu-Arg gave carbamates 4a-4f. Deacetylation of 4b and 4e with MeONa/MeOH gave beta-glucuronides 5b and 5e. Compound 5e was converted to P-glucuronic acid conjugate 6e by the action of pig liver esterase (PLE). Compound 6e is a substrate for beta-glucuronidase. Method of a direct introduction of the prodrug residue into antigenic nonapeptide GILGFVFTL (2b) failed. Alternately, glycine conjugate 5b was activated to pentafluorophenyl ester 10. Model coupling of 10 with Phe-Leu gave tripeptide conjugate ester 11a which was hydrolyzed by PLE to uronic acid 12. Condensation of 10 with octapeptide ILGFVFTL (9) gave prodrug precursor 11b. Octapeptide 9 was prepared by de novo synthesis using a racemization-free fragment coupling method. Ester hydrolysis with Ba(OH)(2)/MeOH gave the target prodrug 2a which is a substrate for beta-glucuronidase. Prodrug 2a does not bind to HLA-A2.1 of T2 human cells defective in major histocompatibility complex I (MHC I)-associated peptide processing. Addition of beta-glucuronidase restored the binding to the level observed with parent nonapeptide 2b although higher concentrations of prodrug 2a and enzyme were necessary.

  DOI：

  10.1021/jm010352w
• 作为产物：
  描述：

  (2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-[4-(2,5-dioxo-pyrrolidin-1-yloxycarbonyloxymethyl)-2-nitro-phenoxy]-tetrahydro-pyran-2-carboxylic acid methyl ester 在 sodium methylate 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.5h， 生成 methyl N-[β-D-glucopyranuronate-3-nitrobenzyloxycarbonyl]glycine pentafluorophenyl ester
  参考文献：
  名称：

  Synthesis and Biological Activity of the Prodrug of Class I Major Histocompatibility Peptide GILGFVFTL Activated by β-Glucuronidase

  摘要：

  The first synthesis of a prodrug of HLA-A.2.1 associated antigenic influenza peptide 2a was accomplished. Two methods for synthesis of prodrugs of antigenic peptides activated by beta-glucuronidase and comprising a self-immolative 3-nitrobenzyloxycarbonyl moiety were investigated. Reaction of P-glucuronic acid glycoside of 4-hydroxy-3-nitrobenzyl alcohol (3) with N,N'-disuccinimidyl carbonate (DSC) followed by conjugation with AlaOMe, Gly, Thr, Phe-Leu, and Leu-Arg gave carbamates 4a-4f. Deacetylation of 4b and 4e with MeONa/MeOH gave beta-glucuronides 5b and 5e. Compound 5e was converted to P-glucuronic acid conjugate 6e by the action of pig liver esterase (PLE). Compound 6e is a substrate for beta-glucuronidase. Method of a direct introduction of the prodrug residue into antigenic nonapeptide GILGFVFTL (2b) failed. Alternately, glycine conjugate 5b was activated to pentafluorophenyl ester 10. Model coupling of 10 with Phe-Leu gave tripeptide conjugate ester 11a which was hydrolyzed by PLE to uronic acid 12. Condensation of 10 with octapeptide ILGFVFTL (9) gave prodrug precursor 11b. Octapeptide 9 was prepared by de novo synthesis using a racemization-free fragment coupling method. Ester hydrolysis with Ba(OH)(2)/MeOH gave the target prodrug 2a which is a substrate for beta-glucuronidase. Prodrug 2a does not bind to HLA-A2.1 of T2 human cells defective in major histocompatibility complex I (MHC I)-associated peptide processing. Addition of beta-glucuronidase restored the binding to the level observed with parent nonapeptide 2b although higher concentrations of prodrug 2a and enzyme were necessary.

  DOI：

  10.1021/jm010352w

文献信息

• Synthesis and Biological Activity of the Prodrug of Class I Major Histocompatibility Peptide GILGFVFTL Activated by β-Glucuronidase
  作者：Sharad Rawale、Lew M. Hrihorczuk、Wei、Jiri Zemlicka

  DOI：10.1021/jm010352w

  日期：2002.2.1

  The first synthesis of a prodrug of HLA-A.2.1 associated antigenic influenza peptide 2a was accomplished. Two methods for synthesis of prodrugs of antigenic peptides activated by beta-glucuronidase and comprising a self-immolative 3-nitrobenzyloxycarbonyl moiety were investigated. Reaction of P-glucuronic acid glycoside of 4-hydroxy-3-nitrobenzyl alcohol (3) with N,N'-disuccinimidyl carbonate (DSC) followed by conjugation with AlaOMe, Gly, Thr, Phe-Leu, and Leu-Arg gave carbamates 4a-4f. Deacetylation of 4b and 4e with MeONa/MeOH gave beta-glucuronides 5b and 5e. Compound 5e was converted to P-glucuronic acid conjugate 6e by the action of pig liver esterase (PLE). Compound 6e is a substrate for beta-glucuronidase. Method of a direct introduction of the prodrug residue into antigenic nonapeptide GILGFVFTL (2b) failed. Alternately, glycine conjugate 5b was activated to pentafluorophenyl ester 10. Model coupling of 10 with Phe-Leu gave tripeptide conjugate ester 11a which was hydrolyzed by PLE to uronic acid 12. Condensation of 10 with octapeptide ILGFVFTL (9) gave prodrug precursor 11b. Octapeptide 9 was prepared by de novo synthesis using a racemization-free fragment coupling method. Ester hydrolysis with Ba(OH)(2)/MeOH gave the target prodrug 2a which is a substrate for beta-glucuronidase. Prodrug 2a does not bind to HLA-A2.1 of T2 human cells defective in major histocompatibility complex I (MHC I)-associated peptide processing. Addition of beta-glucuronidase restored the binding to the level observed with parent nonapeptide 2b although higher concentrations of prodrug 2a and enzyme were necessary.