Methanesulfonic acid (S)-2-[(3R,5S)-5-(4-benzyloxy-benzyl)-morpholin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester | 183794-31-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Methanesulfonic acid (S)-2-[(3R,5S)-5-(4-benzyloxy-benzyl)-morpholin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester
• 英文别名: [(2S)-2-[tert-butyl(dimethyl)silyl]oxy-2-[(3R,5S)-5-[(4-phenylmethoxyphenyl)methyl]morpholin-3-yl]ethyl] methanesulfonate
• CAS: 183794-31-2
• 化学式: C₂₇H₄₁NO₆SSi
• 分子量: 535.777
• InChiKey: UGLDACLTMHNZSJ-SKBVVQJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  91.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methanesulfonic acid (S)-2-[(3R,5S)-5-(4-benzyloxy-benzyl)-morpholin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester 在 钯 五氯化磷 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 63.75h， 生成 (2S,6R,7S,9S)-9-(3-Amino-propyl)-6-chloro-2-(4-hydroxy-benzyl)-8-(2-trimethylsilanyl-ethanesulfonyl)-4-oxa-1,8-diaza-bicyclo[5.3.1]undecan-10-one
  参考文献：
  名称：

  Formation of the 7-Oxa-1,4,10-triazatricyclo[8.2.2^5,12]tetradecane-2,14-dione Ring System:  Misrouted Synthesis of a Peptidomimetic

  摘要：

  An attempted synthesis of the tricyclic peptidomimetic 1, designed to imitate a beta-turn tripeptide in tendamistat, afforded instead the 6,6,8-ring system of 2, The key step in the synthesis entailed acylation of the hindered alpha,alpha'-disubstituted morpholine 4.2, which was approached by acylative ring opening of the 3,6-oxazabicyclo[4.2.0]octane 4.3. However, transannular rather than exocyclic cleavage occurred, giving the 1,6-oxazacyclooctane isomer 4.5. Subsequent ring closures to form the bi- and tricyclic intermediates 7.3 and 8.5 were difficult because of the strain being built into the ring systems. After completion of the synthesis, the structures of the intermediates and final product were elucidated by NMR, with three-bond, heteronuclear multiple-bond correlation experiments providing unambiguous evidence for the ring connectivity, and by molecular modeling, which allowed assignment of the stereochemistry. Compound 2 is a modest inhibitor of the target enzyme alpha-amylase (K-i = 170 mu M in 5% DMSO/water), binding with similar affinity to the tripeptide Ac-Trp-Arg-Tyr-OMe. Although the side-chain attachment points in the ring system of 2 correspond closely to the relative C alpha-positions in tendamistat (rmsd = 0.24 Angstrom), the alignment of the C alpha-C beta bonds is poor, illustrating the importance of side-chain orientation in a peptidomimetic.

  DOI：

  10.1021/jo961114p
• 作为产物：
  描述：

  {(S)-2-(4-Benzyloxy-phenyl)-1-[(Z)-4-(tert-butyl-dimethyl-silanyloxy)-but-2-enyloxymethyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester 在 titanium(IV) isopropylate 、 2,3,5-三甲基吡啶 、 叔丁基过氧化氢 、 氢氟酸 、 D-(-)-酒石酸二异丙酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 50.25h， 生成 Methanesulfonic acid (S)-2-[(3R,5S)-5-(4-benzyloxy-benzyl)-morpholin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester
  参考文献：
  名称：

  Formation of the 7-Oxa-1,4,10-triazatricyclo[8.2.2^5,12]tetradecane-2,14-dione Ring System:  Misrouted Synthesis of a Peptidomimetic

  摘要：

  An attempted synthesis of the tricyclic peptidomimetic 1, designed to imitate a beta-turn tripeptide in tendamistat, afforded instead the 6,6,8-ring system of 2, The key step in the synthesis entailed acylation of the hindered alpha,alpha'-disubstituted morpholine 4.2, which was approached by acylative ring opening of the 3,6-oxazabicyclo[4.2.0]octane 4.3. However, transannular rather than exocyclic cleavage occurred, giving the 1,6-oxazacyclooctane isomer 4.5. Subsequent ring closures to form the bi- and tricyclic intermediates 7.3 and 8.5 were difficult because of the strain being built into the ring systems. After completion of the synthesis, the structures of the intermediates and final product were elucidated by NMR, with three-bond, heteronuclear multiple-bond correlation experiments providing unambiguous evidence for the ring connectivity, and by molecular modeling, which allowed assignment of the stereochemistry. Compound 2 is a modest inhibitor of the target enzyme alpha-amylase (K-i = 170 mu M in 5% DMSO/water), binding with similar affinity to the tripeptide Ac-Trp-Arg-Tyr-OMe. Although the side-chain attachment points in the ring system of 2 correspond closely to the relative C alpha-positions in tendamistat (rmsd = 0.24 Angstrom), the alignment of the C alpha-C beta bonds is poor, illustrating the importance of side-chain orientation in a peptidomimetic.

  DOI：

  10.1021/jo961114p

文献信息

• Formation of the 7-Oxa-1,4,10-triazatricyclo[8.2.2^5,12]tetradecane-2,14-dione Ring System:  Misrouted Synthesis of a Peptidomimetic
  作者：Marisa C. Kozlowski、Paul A. Bartlett

  DOI：10.1021/jo961114p

  日期：1996.1.1

  An attempted synthesis of the tricyclic peptidomimetic 1, designed to imitate a beta-turn tripeptide in tendamistat, afforded instead the 6,6,8-ring system of 2, The key step in the synthesis entailed acylation of the hindered alpha,alpha'-disubstituted morpholine 4.2, which was approached by acylative ring opening of the 3,6-oxazabicyclo[4.2.0]octane 4.3. However, transannular rather than exocyclic cleavage occurred, giving the 1,6-oxazacyclooctane isomer 4.5. Subsequent ring closures to form the bi- and tricyclic intermediates 7.3 and 8.5 were difficult because of the strain being built into the ring systems. After completion of the synthesis, the structures of the intermediates and final product were elucidated by NMR, with three-bond, heteronuclear multiple-bond correlation experiments providing unambiguous evidence for the ring connectivity, and by molecular modeling, which allowed assignment of the stereochemistry. Compound 2 is a modest inhibitor of the target enzyme alpha-amylase (K-i = 170 mu M in 5% DMSO/water), binding with similar affinity to the tripeptide Ac-Trp-Arg-Tyr-OMe. Although the side-chain attachment points in the ring system of 2 correspond closely to the relative C alpha-positions in tendamistat (rmsd = 0.24 Angstrom), the alignment of the C alpha-C beta bonds is poor, illustrating the importance of side-chain orientation in a peptidomimetic.