(2R,4R)-4-Benzyl-2-tert-butyl-5-oxo-oxazolidine-3-carboxylic acid allyl ester | 147240-29-7

• 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: (2R,4R)-4-Benzyl-2-tert-butyl-5-oxo-oxazolidine-3-carboxylic acid allyl ester
• 英文别名: prop-2-enyl (2R,4R)-4-benzyl-2-tert-butyl-5-oxo-1,3-oxazolidine-3-carboxylate
• CAS: 147240-29-7
• 化学式: C₁₈H₂₃NO₄
• 分子量: 317.385
• InChiKey: JMKRTAAWSPXIIZ-GDBMZVCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4R)-4-Benzyl-2-tert-butyl-5-oxo-oxazolidine-3-carboxylic acid allyl ester 在 盐酸 、 sodium hydroxide 、 四(三苯基膦)钯 、 jones reagent 、 氨 、 氯化二乙基铝 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 5,5-二甲基-1,3-环己二酮 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 196.5h， 生成 methyl (2R)-2-[(5S)-5-[(5S)-5-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-5-benzyl-4-oxo-1H-pyrrol-3-yl]-5-(2-methylpropyl)-4-oxo-1H-pyrrol-3-yl]-3-phenylpropanoate
  参考文献：
  名称：

  Pyrrolinone-Based HIV Protease Inhibitors. Design, Synthesis, and Antiviral Activity: Evidence for Improved Transport

  摘要：

  Pyrrolinone-based peptidomimetics, the first mimics of beta-strands, are potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolinones) described herein proved to be more active in cellular antiviral assays compared with an analogous peptide-derived inhibitor even though they are less effective in inhibiting the isolated protease. These results suggest that pyrrolinone inhibitors offer better transport properties than the corresponding peptide-based peptidomimetics; we attribute this effect to decreased solvation of the mimetics. Structure-activity relationships for the pyrrolinones correlate well with those reported for related peptides, consistent with similar modes of binding.

  DOI：

  10.1021/ja00150a011
• 作为产物：
  描述：

  D-苯丙氨酸 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 432.5h， 生成 (2R,4R)-4-Benzyl-2-tert-butyl-5-oxo-oxazolidine-3-carboxylic acid allyl ester
  参考文献：
  名称：

  De Novo Design, Synthesis, and X-ray Crystal Structures of Pyrrolinone-Based .beta.-Strand Peptidomimetics

  摘要：

  The de novo design and synthesis of a novel non-peptide scaffolding for beta-strand/sheet mimics are described. The scaffold consists of repeating 3,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains. The iterative construction of the pyrrolinones exploits a highly efficient cyclization of metalloimines, the latter derived from C-terminal aldehydes and readily available alpha-substituted alpha-amino ester building blocks. As predicted by interactive computer modeling and confirmed by X-ray crystallography, the polypyrrolinones present the side chains and carbonyl hydrogen-bond accepters in a solid-state conformation which mimics polypeptide beta-sheets. Importantly, the enaminone NH protons form hydrogen bonds both intramolecularly, stabilizing the beta-strand conformation, and intermolecularly, promoting sheet formation. The presence or absence of the nitrogen protecting group controlled antiparallel versus parallel sheet formation.

  DOI：

  10.1021/ja00101a017

文献信息

• Enantioretentive alkylation of oxazolidinone aluminum enolates with epoxides: Preparation of uncoded homoserine analogs
  作者：Amos B. Smith、Alexander Pasternak、Akihisa Yokoyama、Ralph Hirschmann

  DOI：10.1016/0040-4039(94)88404-8

  日期：1994.11

  The alkylation of Karady/Seebach oxazolidinone enolates with epoxides, promoted by 2.1 equivalents of diethylaluminum chloride, furnishes ring-opened adducts in moderate-to-good yields with high diastereoselectivity. The method provides an effective approach to uncoded homoserine analogs and expands the utility of readily available oxazolidinones in asymmetric synthesis.

  Karady / Seebach恶唑烷酮烯醇烯酸酯与环氧化物的烷基化，由2.1当量的二乙基氯化铝促进，以中等至良好的收率和高非对映选择性提供开环加合物。该方法为未编码的高丝氨酸类似物提供了有效的方法，并扩大了不对称合成中容易获得的恶唑烷酮的实用性。
• An effective synthesis of scalemic 3,5,5-trisubstituted pyrrolin-4-ones
  作者：Amos B. Smith、Ryan C. Holcomb、Mark C. Guzman、Terence P. Keenan、Paul A. Sprengeler、Ralph Hirschmann

  DOI：10.1016/s0040-4039(00)60058-8

  日期：1993.1

  A new two-step method employs the intramolecular cyclization of metalated imino esters for the construction of scalemic 3,5,5-trisubstituted pyrrolin-4-ones (4). The imino esters in turn derive from alpha-disubstituted amino acids, the latter readily available via a new protocol exploiting the enantioretentive alkylation of oxazolidinones.
• The design and synthesis of 2,5-linked pyrrolinones. A potential non-peptide peptidomimetic scaffold
  作者：Amos B Smith、Steven D Knight、Paul A Sprengeler、Ralph Hirschmann

  DOI：10.1016/0968-0896(96)00094-6

  日期：1996.7

  The de novo design and initial synthetic studies directed toward construction of a novel non-peptide scaffold for beta-strand/sheet and related secondary peptide structural mimics are described. The scaffold, consisting of a repeating array of 2,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains, is conceptually related to our previously successful 3,5-linked polypyrrolinone non-peptide peptidomimetic scaffold. Construction of the 2,5,5-trisubstituted pyrrolinone ring system proceeds via intramolecular condensation of an N-protected amino dione. The latter is prepared from a protected cl-amino ketone and aldehyde via an aldol-oxidation reaction sequence. Copyright (C) 1996 Elsevier Science Ltd
• De Novo Design, Synthesis, and X-ray Crystal Structures of Pyrrolinone-Based .beta.-Strand Peptidomimetics
  作者：Amos B. Smith、Mark C. Guzman、Paul A. Sprengeler、Terence P. Keenan、Ryan C. Holcomb、John L. Wood、Patrick J. Carroll、Ralph Hirschmann

  DOI：10.1021/ja00101a017

  日期：1994.11

  The de novo design and synthesis of a novel non-peptide scaffolding for beta-strand/sheet mimics are described. The scaffold consists of repeating 3,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains. The iterative construction of the pyrrolinones exploits a highly efficient cyclization of metalloimines, the latter derived from C-terminal aldehydes and readily available alpha-substituted alpha-amino ester building blocks. As predicted by interactive computer modeling and confirmed by X-ray crystallography, the polypyrrolinones present the side chains and carbonyl hydrogen-bond accepters in a solid-state conformation which mimics polypeptide beta-sheets. Importantly, the enaminone NH protons form hydrogen bonds both intramolecularly, stabilizing the beta-strand conformation, and intermolecularly, promoting sheet formation. The presence or absence of the nitrogen protecting group controlled antiparallel versus parallel sheet formation.
• Pyrrolinone-Based HIV Protease Inhibitors. Design, Synthesis, and Antiviral Activity: Evidence for Improved Transport
  作者：Amos B Smith、Ralph Hirschmann、Alexander Pasternak、Mark C. Guzman、Akihisa Yokoyama、Paul A. Sprengeler、Paul L. Darke、Emilio A. Emini、William A. Schleif

  DOI：10.1021/ja00150a011

  日期：1995.11

  Pyrrolinone-based peptidomimetics, the first mimics of beta-strands, are potent inhibitors of HIV-1 protease. Importantly, the bis(pyrrolinones) described herein proved to be more active in cellular antiviral assays compared with an analogous peptide-derived inhibitor even though they are less effective in inhibiting the isolated protease. These results suggest that pyrrolinone inhibitors offer better transport properties than the corresponding peptide-based peptidomimetics; we attribute this effect to decreased solvation of the mimetics. Structure-activity relationships for the pyrrolinones correlate well with those reported for related peptides, consistent with similar modes of binding.