(3aR,4S,6aS)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-4,5-dicarboxylic acid 5-(9H-fluoren-9-ylmethyl) ester | 221451-11-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (3aR,4S,6aS)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-4,5-dicarboxylic acid 5-(9H-fluoren-9-ylmethyl) ester
• 英文别名: L-2,3-trans-3,4-cis-N-fluorenylmethoxycarbonyl-3,4-dihydroxy-3,4-O-isopropylidine-proline；(3aR,4S,6aS)-5-(((9H-fluoren-9-yl)methoxy)carbonyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyrrole-4-carboxylic acid；(3aR,4S,6aS)-5-(9H-fluoren-9-ylmethoxycarbonyl)-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-4-carboxylic acid
• CAS: 221451-11-2
• 化学式: C₂₃H₂₃NO₆
• 分子量: 409.439
• InChiKey: RSRPMWQQPKFFDQ-UFYCRDLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3aR,4S,6aS)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-4,5-dicarboxylic acid 5-(9H-fluoren-9-ylmethyl) ester 在 Tesser's base 、 三氟乙酸 作用下， 生成 (2S,3R,4S)-3,4-二羟基吡咯烷-2-羧酸
  参考文献：
  名称：

  Synthesis of l-2,3-trans-3,4-cis-Dihydroxyproline Building Blocks for Peptide Synthesis

  摘要：

  L-2,3-trans-3,4-cis-N-Fluorenylmethoxycarbonyl-3,4-dihydroxy-3,4-O-isopropylidineproline (9) has been prepared from D-gulonolactone in nine steps and an overall yield of 22%. Compound 9 has been converted to its allyl ester 13. Compounds 9 and 13 were investigated as building blocks for the incorporation of dihydroxyproline into peptides, with compound 9 serving as a carboxyl component and compound 13 as a precursor to an amino component for peptide coupling reactions. Their utility was demonstrated by the synthesis of dipeptides 11 and 15.

  DOI：

  10.1021/jo982009d
• 作为产物：
  描述：

  N-fluorenylmethoxycarbonyl-1,4-dideoxy-2,3-O-isopropylidene-1,4-imino-D-allitol 在 sodium chlorite 、 sodium periodate 、 potassium dihydrogenphosphate 、 环己烯 作用下， 以 乙醇 、 水 、 叔丁醇 为溶剂， 反应 12.25h， 生成 (3aR,4S,6aS)-2,2-dimethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-4,5-dicarboxylic acid 5-(9H-fluoren-9-ylmethyl) ester
  参考文献：
  名称：

  Synthesis of l-2,3-trans-3,4-cis-Dihydroxyproline Building Blocks for Peptide Synthesis

  摘要：

  L-2,3-trans-3,4-cis-N-Fluorenylmethoxycarbonyl-3,4-dihydroxy-3,4-O-isopropylidineproline (9) has been prepared from D-gulonolactone in nine steps and an overall yield of 22%. Compound 9 has been converted to its allyl ester 13. Compounds 9 and 13 were investigated as building blocks for the incorporation of dihydroxyproline into peptides, with compound 9 serving as a carboxyl component and compound 13 as a precursor to an amino component for peptide coupling reactions. Their utility was demonstrated by the synthesis of dipeptides 11 and 15.

  DOI：

  10.1021/jo982009d

文献信息

• Scaling the Amphiphilic Character and Antimicrobial Activity of Gramicidin S by Dihydroxylation or Ketal Formation
  作者：Christoph Priem、André Wuttke、Marina Berditsch、Anne S. Ulrich、Armin Geyer

  DOI：10.1021/acs.joc.7b02177

  日期：2017.12.1

  at the position of d-Phe1-Pro2 eradicates the biological activity (GS mimetic 16). The acid-stable ketals 17–19 are bioorthogonal modifications which reconstitute the biological activity of GS. We describe an improved synthesis of orthogonally protected Fmoc-Dyp-acetonide (9) and of several Fmoc-d-Hot═Tap-ketals for solid-phase peptide synthesis.

  脂肪族缩酮的酸不稳定性通常受1,2-二醇保护基的影响，受其局部结构环境的影响。被保护的氨基酸顺式-二羟基脯氨酸（Dyp）的丙酮化物是典型的可被痕量的TFA裂解的保护基。二肽d- Hot═Tap的三环丙酮化物对TFA具有抗性，因此可以用作生物活性肽的生物正交修饰。为了提高抗菌活性和溶血特性，我们使用这些反应性差异来缩放十肽格米星素S环（d -Phe-Pro-Val-Orn-Leu-）2（GS）的膜亲和力。该顺-二羟基化氨基酸用于通过与脂肪族酮的立体选择性缩酮形成来增加GS的极性或相反地降低极性。虽然Dyp（GS模拟物15）对GS的生物学特性影响很小，但d- Phe1 -Pro2位置的d - Hot═Tap消除了生物活性（GS模拟物16）。酸稳定的缩酮17 – 19是生物正交修饰，可重构GS的生物活性。我们描述正交保护的Fmoc-DYP丙酮（的改进的合成9）和几个的Fmoc- d-Hot═Tap-缩酮，用于固相肽合成。
• Synthesis of the Repeating Decapeptide Unit of Mefp1 in Orthogonally Protected Form
  作者：Carol M. Taylor、Claudette A. Weir

  DOI：10.1021/jo991523w

  日期：2000.3.1

  homogeneous oligopeptides based on the repeating decapeptide unit of the protein. The fully protected decapeptide 10 has been synthesized from appropriately protected amino acid building blocks using a fragment condensation strategy. A key feature of the strategy is the late incorporation of the synthetically valuable dihydroxyproline residue. This synthesis of the orthogonally protected repeating decapeptide

  Mefp1是由海洋贻贝（Mytilus edulis）产生的一种蛋白质，可帮助生物粘附在湍流水中的表面。为了更好地理解粘附过程的性质，我们试图基于蛋白质的重复十肽单元合成均质的寡肽。完全保护的十肽10已使用片段缩合策略由适当保护的氨基酸构件合成。该策略的关键特征是合成有价值的二羟基脯氨酸残基的后期结合。Mefp1的正交保护的重复十肽单元的这种合成代表了重要的第一步，该第一步迈向了生产有用量的与蛋白质相关的均质寡肽。
• The Impact of Pyrrolidine Hydroxylation on the Conformation of Proline-Containing Peptides
  作者：Carol M. Taylor、Renaud Hardré、Patrick J. B. Edwards

  DOI：10.1021/jo0490043

  日期：2005.2.1

  [GRAPHICS]A series of eight dipeptides of the general formula Ac-Phe-Pro*-NHMe was synthesized and the thermodynamics of the cis --> trans isomerization about the central amide bond were studied by NMR. Pro* represents the following prolines: L-proline (Pro), L-trans-4-hydroxyproline (Hyp), L-cis-4-hydroxyproline (hyp), L-cis-4-methoxyproline (hyp[OMe]), L-trans-3-hydroxyproline (3-Hyp), L-cis-3-hydroxyproline (3-hyp), L-2,3-trans-3,4-cis-3,4-dihydroxyproline (DHP), and L-2,3-cis-3,4-trans3,4-dihydroxyproline (dhp). The conformation of the pyrrolidine ring in each case is discussed in light of previous structural studies, analysis of potential stereoelectronic effects, and NMR data. Hydroxy substituents at C-4 have a greater impact on cis --> trans isomerization than analogous substituents at C-3 as a result of the intervening bond distances and bridging groups. The position of the equilibrium and its dependence on temperature are a reflection of both enthalpic and entropic factors, the latter being complicated in this study by an Ar-Pro interaction in the cis conformation. The substituents on the pyrrolidine ring determine the conformation of the five-membered ring, which in turn influences the strength of the Ar-Pro interaction, backbone dihedral angles, and the relative energy of the cis and trans species. The ultimate position of the equilibrium depends on a complex blend of steric, electronic, and conformational factors.