di-tert-butyl (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylate | 480460-58-0

• 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: di-tert-butyl (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylate
• 英文别名: di(tert-butyl)-(2S,5R)-5-hydroxy-6-oxotetrahydro-1,2(2H)-pyridinedicarboxylate；ditert-butyl (2S,5R)-5-hydroxy-6-oxopiperidine-1,2-dicarboxylate
• CAS: 480460-58-0
• 化学式: C₁₅H₂₅NO₆
• 分子量: 315.367
• InChiKey: FGSUUBHRWUOQNH-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylate 在 2,3,5-三甲基吡啶 、 sodium tetrahydroborate 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 40.0h， 生成 (2S,5R)-(+)-tert-butyl 2-[(tert-butoxycarbonyl)amino]-5-hydroxy-6-iodohexanoate
  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：

  (S)-6-oxo-N-(tert-butyloxycarbonyl)-pipecolic acid tert-butyl ester 在 lithium hexamethyldisilazane 、 (+)-(10-camphorsulfonyl)oxaziridine 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 以92%的产率得到di-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

文献信息

• Galactosylated 5-Hydroxylysine Mimetics for Glycopeptide Synthesis
  作者：Julien Marin、Aude Violette、Jean-Paul Briand、Gilles Guichard

  DOI：10.1002/ejoc.200400119

  日期：2004.7

  Our approach features: i) a short and divergent route to the corresponding protected amino acid aglycons 6−9 that involves selective ring-opening of enantiopure 5-hydroxylated 6-oxo-1,2-piperidinedicarboxylate 10 and 11 with sodium borohydride in ethanol with formation of the corresponding 1,2-diol; ii) a common δ-lactam precursor 12, readily accessible from Boc-Asp-OtBu (3 steps, 74% yield), that

  描述了四种半乳糖基化 5-羟基赖氨酸模拟构件 (2-5) 的设计和合成，可方便地保护固相糖肽合成。我们的方法特点：i) 对应受保护氨基酸苷元 6-9 的短而不同的路线，包括对映纯 5-羟基化 6-氧代-1,2-哌啶二羧酸酯 10 和 11 的选择性开环与硼氢化钠的乙醇溶液形成相应的1,2-二醇；ii) 一种常见的 δ-内酰胺前体 12，很容易从 Boc-Asp-OtBu 中获得（3 步，74% 产率），可以在高水平的不对称诱导下羟基化；iii) 使用四新戊酰化半乳糖基溴作为半乳糖基供体以避免或限制原酸酯形成。四种半乳糖基化羟赖氨酸类似物 2-5 是合适的构建块，可用于整合到源自 II 型胶原蛋白 (CII) 的免疫优势肽中，并用于未来的研究，旨在确定胶原诱导性关节炎 (CIA) 中致关节炎 T 细胞的精细特异性，这是一种类风湿性关节炎 (RA) 小鼠模型。(© Wiley-VCH Verlag