Methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-L-glycero-α-D-gluco-heptopyranosiduronic acid benzyl ester | 161147-43-9

• 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: Methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-L-glycero-α-D-gluco-heptopyranosiduronic acid benzyl ester
• 英文别名: benzyl (2R)-2-acetamido-2-[(2R,3R,4S,5R,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]acetate
• CAS: 161147-43-9
• 化学式: C₃₈H₄₁NO₈
• 分子量: 639.745
• InChiKey: WPKGQKCPSNCBPD-MYWXGXDKSA-N

物化性质

• 沸点：
  760.0±60.0 °C(predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  47
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-L-glycero-α-D-gluco-heptopyranosiduronic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以93%的产率得到Methyl 6-(N-acetylamino)-6-deoxy-L-glycero-α-D-gluco-heptopyranosiduronic acid
  参考文献：
  名称：

  Chain-Extension of Carbohydrates. 5. Synthesis of the C-Glycosyl Amino Acid Moiety of Miharamycins Involving Stereocontrolled Ethynylation of Methyl 2,3,4-Tri-O-benzyl-.alpha.-D-gluco-hexodialdo-1,5-pyranoside

  摘要：

  A multistep synthesis of the C-glycosyl amino acid moiety of miharamycins from methyl 2,3,4-tri-O-benzyl-alpha-D-gluco-hexodialdo-1,5-pyranoside (1) is described, The ethynyl group was employed as a synthetic equivalent of the carboxylic acid function, In the key step, highly diastereoselective ethynylation of compound 1 with the Grignard reagent of (trimethylsilyl)acetylene in the presence of magnesium bromide followed by desilylation afforded acetylenic alcohols 4 and 5 (19:1). The L-glycero configuration at C(6) of the major isomer 4 was unambiguously proven by H-1 NMR of the 4,6-benzylidene derivative 9. The amino function was introduced at C(6) by reaction of 4 with zinc azide in the presence of triphenylphosphine and diisopropyl azodicarboxylate. Transformation of the resulting methyl 6-azido-2,3,4-tri-O-benzyl-6,7,8-trideoxy side (10) into methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-D-glycero-alpha-D-gluco-heptopyranosiduronic acid (17) was achieved by two different sequences of reactions: (1) oxidative cleavage of the triple bond, benzylation, reduction of the azido group, and N-acetylation or (2) reduction of the azido group, N-acetylation, oxidative cleavage of the triple bond, and treatment with phenyldiazomethane. The overall yield of the two sequences was different (41% versus 50%), showing the second method to be superior. Final debenzylation afforded methyl 6-(N-acetylamino)6-deoxy-L-glycero-alpha-D-gluco-heptopyranisoduronic acid (18). To prepare the epimeric amino acid derivative 28, the configuration at C(6) of 4 was inverted by a Mitsunobu reaction. The same sequence of reactions was applied to the so-obtained D-glycero isomer 5 and methyl 6-(N-acetyl-amino)-6-deoxy-L-glycero-alpha-D-gluco-heptopyranosiduronic acid (28) was obtained. In this case almost identical overall yields were obtained for the two different transformations of the azidoalkyne 20 to compound 28 (62% versus 63%).

  DOI：

  10.1021/jo00108a030
• 作为产物：
  描述：

  methyl 6-aldehydo-2,3,4-tri-O-benzyl-α-D-glucopyranoside 在 吡啶 、 1,3-丙二硫醇 、 sodium periodate 、 四氧化锇 、 正丁基锂 、 Zn(N₃)₂*Py₂ 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 magnesium bromide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 48.58h， 生成 Methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-L-glycero-α-D-gluco-heptopyranosiduronic acid benzyl ester
  参考文献：
  名称：

  Chain-Extension of Carbohydrates. 5. Synthesis of the C-Glycosyl Amino Acid Moiety of Miharamycins Involving Stereocontrolled Ethynylation of Methyl 2,3,4-Tri-O-benzyl-.alpha.-D-gluco-hexodialdo-1,5-pyranoside

  摘要：

  A multistep synthesis of the C-glycosyl amino acid moiety of miharamycins from methyl 2,3,4-tri-O-benzyl-alpha-D-gluco-hexodialdo-1,5-pyranoside (1) is described, The ethynyl group was employed as a synthetic equivalent of the carboxylic acid function, In the key step, highly diastereoselective ethynylation of compound 1 with the Grignard reagent of (trimethylsilyl)acetylene in the presence of magnesium bromide followed by desilylation afforded acetylenic alcohols 4 and 5 (19:1). The L-glycero configuration at C(6) of the major isomer 4 was unambiguously proven by H-1 NMR of the 4,6-benzylidene derivative 9. The amino function was introduced at C(6) by reaction of 4 with zinc azide in the presence of triphenylphosphine and diisopropyl azodicarboxylate. Transformation of the resulting methyl 6-azido-2,3,4-tri-O-benzyl-6,7,8-trideoxy side (10) into methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-D-glycero-alpha-D-gluco-heptopyranosiduronic acid (17) was achieved by two different sequences of reactions: (1) oxidative cleavage of the triple bond, benzylation, reduction of the azido group, and N-acetylation or (2) reduction of the azido group, N-acetylation, oxidative cleavage of the triple bond, and treatment with phenyldiazomethane. The overall yield of the two sequences was different (41% versus 50%), showing the second method to be superior. Final debenzylation afforded methyl 6-(N-acetylamino)6-deoxy-L-glycero-alpha-D-gluco-heptopyranisoduronic acid (18). To prepare the epimeric amino acid derivative 28, the configuration at C(6) of 4 was inverted by a Mitsunobu reaction. The same sequence of reactions was applied to the so-obtained D-glycero isomer 5 and methyl 6-(N-acetyl-amino)-6-deoxy-L-glycero-alpha-D-gluco-heptopyranosiduronic acid (28) was obtained. In this case almost identical overall yields were obtained for the two different transformations of the azidoalkyne 20 to compound 28 (62% versus 63%).

  DOI：

  10.1021/jo00108a030

文献信息

• Chain-Extension of Carbohydrates. 5. Synthesis of the C-Glycosyl Amino Acid Moiety of Miharamycins Involving Stereocontrolled Ethynylation of Methyl 2,3,4-Tri-O-benzyl-.alpha.-D-gluco-hexodialdo-1,5-pyranoside
  作者：Stanislas Czernecki、Stefan Horns、Jean-Marc Valery

  DOI：10.1021/jo00108a030

  日期：1995.2

  A multistep synthesis of the C-glycosyl amino acid moiety of miharamycins from methyl 2,3,4-tri-O-benzyl-alpha-D-gluco-hexodialdo-1,5-pyranoside (1) is described, The ethynyl group was employed as a synthetic equivalent of the carboxylic acid function, In the key step, highly diastereoselective ethynylation of compound 1 with the Grignard reagent of (trimethylsilyl)acetylene in the presence of magnesium bromide followed by desilylation afforded acetylenic alcohols 4 and 5 (19:1). The L-glycero configuration at C(6) of the major isomer 4 was unambiguously proven by H-1 NMR of the 4,6-benzylidene derivative 9. The amino function was introduced at C(6) by reaction of 4 with zinc azide in the presence of triphenylphosphine and diisopropyl azodicarboxylate. Transformation of the resulting methyl 6-azido-2,3,4-tri-O-benzyl-6,7,8-trideoxy side (10) into methyl 6-(N-acetylamino)-2,3,4-tri-O-benzyl-6-deoxy-D-glycero-alpha-D-gluco-heptopyranosiduronic acid (17) was achieved by two different sequences of reactions: (1) oxidative cleavage of the triple bond, benzylation, reduction of the azido group, and N-acetylation or (2) reduction of the azido group, N-acetylation, oxidative cleavage of the triple bond, and treatment with phenyldiazomethane. The overall yield of the two sequences was different (41% versus 50%), showing the second method to be superior. Final debenzylation afforded methyl 6-(N-acetylamino)6-deoxy-L-glycero-alpha-D-gluco-heptopyranisoduronic acid (18). To prepare the epimeric amino acid derivative 28, the configuration at C(6) of 4 was inverted by a Mitsunobu reaction. The same sequence of reactions was applied to the so-obtained D-glycero isomer 5 and methyl 6-(N-acetyl-amino)-6-deoxy-L-glycero-alpha-D-gluco-heptopyranosiduronic acid (28) was obtained. In this case almost identical overall yields were obtained for the two different transformations of the azidoalkyne 20 to compound 28 (62% versus 63%).