((3R,4S,5S,7R,11R,12R,E)-12-ethyl-3,5,7,11-tetramethyl-2,8-dioxo-1-oxacyclododec-9-en-4-yl) 3-(dimethylamino)propanoate | 1583315-15-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: ((3R,4S,5S,7R,11R,12R,E)-12-ethyl-3,5,7,11-tetramethyl-2,8-dioxo-1-oxacyclododec-9-en-4-yl) 3-(dimethylamino)propanoate
• 英文别名: [(3r,4s,5s,7r,9e,11r,12r)-12-Ethyl-3,5,7,11-Tetramethyl-2,8-Bis(Oxidanylidene)-1-Oxacyclododec-9-En-4-Yl] 3-(Dimethylamino)propanoate；[(3R,4S,5S,7R,9E,11R,12R)-12-ethyl-3,5,7,11-tetramethyl-2,8-dioxo-1-oxacyclododec-9-en-4-yl] 3-(dimethylamino)propanoate
• CAS: 1583315-15-4
• 化学式: C₂₂H₃₇NO₅
• 分子量: 395.539
• InChiKey: ARTBSYNHBBHIBV-HSYQSNAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((3R,4S,5S,7R,11R,12R,E)-12-ethyl-3,5,7,11-tetramethyl-2,8-dioxo-1-oxacyclododec-9-en-4-yl) 3-(dimethylamino)propanoate 在 nicotinamide adenine dinucleotide phosphate 、 glucose-6-phosphate dehydrogenase 、 PikC_D50N-RhFRED 作用下， 以 aq. phosphate buffer 为溶剂， 反应 3.0h， 生成 、 (3R,4S,5S,7R,11R,12S,E)-12-((R)-1-hydroxyethyl)-3,5,7,11-tetramethyl-2,8-dioxooxacyclododec-9-en-4-yl 3-(dimethylamino)propanoate
  参考文献：
  名称：

  Directing Group-Controlled Regioselectivity in an Enzymatic C–H Bond Oxygenation

  摘要：

  Highly regioselective remote hydroxylation of a natural product scaffold is demonstrated by exploiting the anchoring mechanism of the biosynthetic P450 monooxygenase PikC(D50N)-RhFRED. Previous studies have revealed structural and biochemical evidence for the role of a salt bridge between the desosamine N,N-dimethylamino functionality of the natural substrate YC-17 and carboxylate residues within the active site of the enzyme, and selectivity in subsequent C-H bond functionalization. In the present study, a substrate-engineering approach was conducted that involves replacing desosamine with varied synthetic N,N-dimethylamino anchoring groups. We then determined their ability to mediate enzymatic total turnover numbers approaching or exceeding that of the natural sugar, while enabling ready introduction and removal of these amino anchoring groups from the substrate. The data establish that the size, stereochemistry, and rigidity of the anchoring group influence the regioselectivity of enzymatic hydroxylation. The natural anchoring group desosamine affords a 1:1 mixture of regioisomers, while synthetic anchors shift YC-17 analogue C-10/C-12 hydroxylation from 20:1 to 1:4. The work demonstrates the utility of substrate engineering as an orthogonal approach to protein engineering for modulation of regioselective C-H functionalization in biocatalysis.

  DOI：

  10.1021/ja5016052
• 作为产物：
  描述：

  3-二甲基氨基丙酸盐酸盐 、 10-去氧微甘菊内酯 在 4-二甲氨基吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 144.0h， 以34%的产率得到((3R,4S,5S,7R,11R,12R,E)-12-ethyl-3,5,7,11-tetramethyl-2,8-dioxo-1-oxacyclododec-9-en-4-yl) 3-(dimethylamino)propanoate
  参考文献：
  名称：

  Directing Group-Controlled Regioselectivity in an Enzymatic C–H Bond Oxygenation

  摘要：

  Highly regioselective remote hydroxylation of a natural product scaffold is demonstrated by exploiting the anchoring mechanism of the biosynthetic P450 monooxygenase PikC(D50N)-RhFRED. Previous studies have revealed structural and biochemical evidence for the role of a salt bridge between the desosamine N,N-dimethylamino functionality of the natural substrate YC-17 and carboxylate residues within the active site of the enzyme, and selectivity in subsequent C-H bond functionalization. In the present study, a substrate-engineering approach was conducted that involves replacing desosamine with varied synthetic N,N-dimethylamino anchoring groups. We then determined their ability to mediate enzymatic total turnover numbers approaching or exceeding that of the natural sugar, while enabling ready introduction and removal of these amino anchoring groups from the substrate. The data establish that the size, stereochemistry, and rigidity of the anchoring group influence the regioselectivity of enzymatic hydroxylation. The natural anchoring group desosamine affords a 1:1 mixture of regioisomers, while synthetic anchors shift YC-17 analogue C-10/C-12 hydroxylation from 20:1 to 1:4. The work demonstrates the utility of substrate engineering as an orthogonal approach to protein engineering for modulation of regioselective C-H functionalization in biocatalysis.

  DOI：

  10.1021/ja5016052

文献信息

• Directing Group-Controlled Regioselectivity in an Enzymatic C–H Bond Oxygenation
  作者：Solymar Negretti、Alison R. H. Narayan、Karoline C. Chiou、Petrea M. Kells、Jessica L. Stachowski、Douglas A. Hansen、Larissa M. Podust、John Montgomery、David H. Sherman

  DOI：10.1021/ja5016052

  日期：2014.4.2

  Highly regioselective remote hydroxylation of a natural product scaffold is demonstrated by exploiting the anchoring mechanism of the biosynthetic P450 monooxygenase PikC(D50N)-RhFRED. Previous studies have revealed structural and biochemical evidence for the role of a salt bridge between the desosamine N,N-dimethylamino functionality of the natural substrate YC-17 and carboxylate residues within the active site of the enzyme, and selectivity in subsequent C-H bond functionalization. In the present study, a substrate-engineering approach was conducted that involves replacing desosamine with varied synthetic N,N-dimethylamino anchoring groups. We then determined their ability to mediate enzymatic total turnover numbers approaching or exceeding that of the natural sugar, while enabling ready introduction and removal of these amino anchoring groups from the substrate. The data establish that the size, stereochemistry, and rigidity of the anchoring group influence the regioselectivity of enzymatic hydroxylation. The natural anchoring group desosamine affords a 1:1 mixture of regioisomers, while synthetic anchors shift YC-17 analogue C-10/C-12 hydroxylation from 20:1 to 1:4. The work demonstrates the utility of substrate engineering as an orthogonal approach to protein engineering for modulation of regioselective C-H functionalization in biocatalysis.