2-benzyl 1-tert-butyl (2S)-6-oxo-1,2-piperidinedicarboxylate | 176436-12-7

• 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: 2-benzyl 1-tert-butyl (2S)-6-oxo-1,2-piperidinedicarboxylate
• 英文别名: 2-Benzyl 1-(tert-butyl) (S)-6-oxopiperidine-1,2-dicarboxylate；2-O-benzyl 1-O-tert-butyl (2S)-6-oxopiperidine-1,2-dicarboxylate
• CAS: 176436-12-7
• 化学式: C₁₈H₂₃NO₅
• 分子量: 333.384
• InChiKey: JSHVSMAONLSKJT-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyl 1-tert-butyl (2S)-6-oxo-1,2-piperidinedicarboxylate 在 lithium hexamethyldisilazane 、 (+)-(10-camphorsulfonyl)oxaziridine 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 以88%的产率得到2-benzyl 1-tert-butyl (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylate
  参考文献：
  名称：

  Diastereoselective Hydroxylation of 6-Substituted Piperidin-2-ones. An Efficient Synthesis of (2S,5R)-5-Hydroxylysine and Related α-Amino Acids

  摘要：

  The synthesis of (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylates (5) and related (3S,W-3hydroxy-6-alkyl-2-oxo-1-piperidinecarboxylates has been developed. The approach is based on the asymmetric hydroxylation of enolates generated from the corresponding N-protected-6-substituted piperidin-2-ones. The utility of 5a as a precursor in the synthesis of (2S,5R)-5-hydroxylysine (1), an amino acid unique to collagen and collagen-like proteins, has also been demonstrated. (2S)-6oxo-1,2-piperidinedicarboxylates (6) required for hydroxylation studies were prepared in 38-74% yield, starting from conveniently protected aspartic acid as inexpensive chiral adduct. Hydroxylation of 6 to 5 proceeds in high yield and excellent diastereoselectivity by treatment of their Li-enolate with (+)-camphorsulfonyloxaziridine at -78 degreesC. Ring opening of di-tert-butyl (2S,5R)-6-oxo-1,2-piperidinedicarboxylate ((5R)-5a) under reductive conditions afforded the corresponding 1,2-diol (17) in 91%, which was further transformed to (2S,5R)-5-hydroxylysine in four steps (84%). 17 is also a versatile intermediate in the preparation of tert-butyl (2S,M)-2-[(tert-butoxycarbonyl)aminol 5-hydroxy-6-iodohexanoate (3) and tert-butyl (2S)-2-[(tert-butoxycarbonyl)aminol-4-[(2,R)-oxiranyl]- butanoate (4), two amino acid derivatives used in the total synthesis of the bone collagen cross-link (+)-pyridinoline (2a).

  DOI：

  10.1021/jo025950c
• 作为产物：
  描述：

  Boc-L-天冬氨酸 1-苄酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 51.0h， 生成 2-benzyl 1-tert-butyl (2S)-6-oxo-1,2-piperidinedicarboxylate
  参考文献：
  名称：

  Diastereoselective Hydroxylation of 6-Substituted Piperidin-2-ones. An Efficient Synthesis of (2S,5R)-5-Hydroxylysine and Related α-Amino Acids

  摘要：

  The synthesis of (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylates (5) and related (3S,W-3hydroxy-6-alkyl-2-oxo-1-piperidinecarboxylates has been developed. The approach is based on the asymmetric hydroxylation of enolates generated from the corresponding N-protected-6-substituted piperidin-2-ones. The utility of 5a as a precursor in the synthesis of (2S,5R)-5-hydroxylysine (1), an amino acid unique to collagen and collagen-like proteins, has also been demonstrated. (2S)-6oxo-1,2-piperidinedicarboxylates (6) required for hydroxylation studies were prepared in 38-74% yield, starting from conveniently protected aspartic acid as inexpensive chiral adduct. Hydroxylation of 6 to 5 proceeds in high yield and excellent diastereoselectivity by treatment of their Li-enolate with (+)-camphorsulfonyloxaziridine at -78 degreesC. Ring opening of di-tert-butyl (2S,5R)-6-oxo-1,2-piperidinedicarboxylate ((5R)-5a) under reductive conditions afforded the corresponding 1,2-diol (17) in 91%, which was further transformed to (2S,5R)-5-hydroxylysine in four steps (84%). 17 is also a versatile intermediate in the preparation of tert-butyl (2S,M)-2-[(tert-butoxycarbonyl)aminol 5-hydroxy-6-iodohexanoate (3) and tert-butyl (2S)-2-[(tert-butoxycarbonyl)aminol-4-[(2,R)-oxiranyl]- butanoate (4), two amino acid derivatives used in the total synthesis of the bone collagen cross-link (+)-pyridinoline (2a).

  DOI：

  10.1021/jo025950c

文献信息

• The enantiospecific synthesis of functionalised pipecolic acids as constrained analogues of lysine
  作者：Peter John Murray、Ian D. Starkey

  DOI：10.1016/0040-4039(96)00140-2

  日期：1996.3

  Two constrained analogues of (S)- lysine have been prepared, suitably protected for solid phase peptide synthesis, in high optical and diastereomeric purity. The key step is the alkylation of the 6-oxopipecolate derivative (6) with iodoacetonitrile.

  已经制备了两个受约束的（S）-赖氨酸类似物，它们以高光学和非对映异构体纯度被适当地保护用于固相肽合成。关键步骤是将6-氧代戊酸酯衍生物（6）与碘乙腈进行烷基化。
• 2,5-Disubstituted Piperidines
  申请人：Herold Peter

  公开号：US20090306062A1

  公开（公告）日：2009-12-10

  The application relates to 2,5-disubstituted piperidines, their preparation and use as medicines, especially as renin inhibitors, of the general formula (I) in which R, R 1 and X are each as defined in detail in the description, and pharmaceutical preparations comprising these compounds.

  该申请涉及2,5-二取代哌啶的制备和用途，特别是作为肾素抑制剂的药物。所述化合物的通式为（I），其中R、R1和X的详细定义在说明书中，以及包含这些化合物的制药制剂。
• Diastereoselective Hydroxylation of 6-Substituted Piperidin-2-ones. An Efficient Synthesis of (2<i>S</i>,5<i>R</i>)-5-Hydroxylysine and Related α-Amino Acids
  作者：J. Marin、C. Didierjean、A. Aubry、Briand、G. Guichard

  DOI：10.1021/jo025950c

  日期：2002.11.1

  The synthesis of (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylates (5) and related (3S,W-3hydroxy-6-alkyl-2-oxo-1-piperidinecarboxylates has been developed. The approach is based on the asymmetric hydroxylation of enolates generated from the corresponding N-protected-6-substituted piperidin-2-ones. The utility of 5a as a precursor in the synthesis of (2S,5R)-5-hydroxylysine (1), an amino acid unique to collagen and collagen-like proteins, has also been demonstrated. (2S)-6oxo-1,2-piperidinedicarboxylates (6) required for hydroxylation studies were prepared in 38-74% yield, starting from conveniently protected aspartic acid as inexpensive chiral adduct. Hydroxylation of 6 to 5 proceeds in high yield and excellent diastereoselectivity by treatment of their Li-enolate with (+)-camphorsulfonyloxaziridine at -78 degreesC. Ring opening of di-tert-butyl (2S,5R)-6-oxo-1,2-piperidinedicarboxylate ((5R)-5a) under reductive conditions afforded the corresponding 1,2-diol (17) in 91%, which was further transformed to (2S,5R)-5-hydroxylysine in four steps (84%). 17 is also a versatile intermediate in the preparation of tert-butyl (2S,M)-2-[(tert-butoxycarbonyl)aminol 5-hydroxy-6-iodohexanoate (3) and tert-butyl (2S)-2-[(tert-butoxycarbonyl)aminol-4-[(2,R)-oxiranyl]- butanoate (4), two amino acid derivatives used in the total synthesis of the bone collagen cross-link (+)-pyridinoline (2a).