(S)-Azido-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-acetic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-Azido-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-acetic acid
• 英文别名: (2S)-2-azido-2-[(2R,3R,4S,5R,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]acetic acid
• 化学式: C₂₉H₃₁N₃O₇
• 分子量: 533.581
• InChiKey: OPLBAIRMIVRXEX-RJLPFZRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-Azido-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-acetic acid 在 镍 氢气 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 (S)-Amino-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-acetic 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
• 作为产物：
  描述：

  methyl 6-aldehydo-2,3,4-tri-O-benzyl-α-D-glucopyranoside 在 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 、 三苯基膦 、 magnesium bromide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.25h， 生成 (S)-Azido-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-acetic 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

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%).