N-(9H-fluoren-9-ylmethoxycarbonyl)-D-serine benzyl ester | 118358-66-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(9H-fluoren-9-ylmethoxycarbonyl)-D-serine benzyl ester
• 英文别名: N-fluorenylmethoxycarbonyl-D-serine benzyl ester；N-(9-fluorenylmethoxycarbonyl)-D-serine-benzyl ester；N-Fmoc-D-serine；(R)-Benzyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-hydroxypropanoate；benzyl (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-hydroxypropanoate
• CAS: 118358-66-0
• 化学式: C₂₅H₂₃NO₅
• 分子量: 417.461
• InChiKey: GXJVEJVEJKIXCH-HSZRJFAPSA-N

物化性质

• 沸点：
  656.2±55.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(9H-fluoren-9-ylmethoxycarbonyl)-D-serine benzyl ester 在 吡啶 、 silver perchlorate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-acetyl-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester
  参考文献：
  名称：

  Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis

  摘要：

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.

  DOI：

  10.1021/ja212188r
• 作为产物：
  描述：

  N-(9H-fluoren-9-ylmethoxycarbonyl)-O-trityl-D-serine benzyl ester 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 以85%的产率得到N-(9H-fluoren-9-ylmethoxycarbonyl)-D-serine benzyl ester
  参考文献：
  名称：

  Efficient Solid-Phase-Based Total Synthesis of the Bisintercalator TANDEM

  摘要：

  In this article, the first solid-phase-based total synthesis of TANDEM, a synthetic analogue of triostin A, is described. In initial studies, the synthesis incorporated depsipeptide formation, introduction of chromophores, and disulfide bond formation on the solid phase, prior to a final solution-phase macrolactamization, to give the target molecule. Although pure TANDEM was obtained in an overall yield comparable to those for all syntheses to date, the yield of the final cyclization was low (11%). A more efficient approach involved removal from the solid phase prior to disulfide bond formation. The resulting linear peptide underwent macrolactamization under mild conditions and high dilution. Final disulfide bond formation was essentially quantitative and gave the target molecule, TANDEM, in an overall yield of 18%. The final compound was assessed for its ability to bind to 5'-TpA sequences on DNA by DNase I footprinting. This efficient synthesis sets the stage for a study of the structure-activity relationship of TANDEM and the natural product triostin A, with analogues containing "point mutations" at every site within the cyclic compounds.

  DOI：

  10.1021/jo050959a

文献信息

• Progress toward the assembly of the bicyclic theonellamide skeleton
  作者：Jyoti P. Mukherjee、Joyeeta Roy、Chyree S. Batton、Saroj Yadav、Douglas Wong、Carol M. Taylor

  DOI：10.1016/j.tet.2020.131127

  日期：2020.4

  synthesized in solution. Each ring was formed independently, providing insights into protecting group limitations, side reactions, and the optimal order of events to approach the formation of the bicyclic system. Ultimately, an undecapeptide was prepared, with the eastern ring formed. The twelfth amino acid, an l-α-aminoadipic acid building block, was prepared and preliminary investigations into its attachment

  的正交保护的τ-histidinoalanine残余物通过旋光纯的Boc-的区域选择性烷基化，合成升与亲电子从的Fmoc-衍生的磺酰胺酯-His-OTCE（TCE =三氯乙基）d -Ser-OBn的 目的是合成一种非天然的theonellamide，并调用其他10个氨基酸的易于获得的变体。在溶液中合成了与“ theonellamide X”的东环和西环相对应的肽片段。每个环都是独立形成的，可深入了解保护基团的限制，副反应以及接近双环系统形成的最佳事件顺序。最终，制备了十一肽，形成了东环。第十二氨基酸，升制备了-α-氨基己二酸构件，并报道了其与十一肽的连接的初步研究。
• 一种N-芴甲氧羰基-O-辛酰基-丝/苏氨酸的制备方法
  申请人：吉尔生化（上海）有限公司

  公开号：CN109627185A

  公开（公告）日：2019-04-16

  本发明涉及一种N‑芴甲氧羰基‑O‑辛酰基‑丝/苏氨酸的制备方法，主要解决现有合成方法的操作难度大，且难以提纯以及放大生产中不环保的技术问题。本发明的技术方案为：一种N‑芴甲氧羰基‑O‑辛酰基‑丝/苏氨酸的制备方法，包括以下步骤：由N‑芴甲氧羰基‑丝/苏氨酸‑苄酯为起始原料，与正辛酸通过加入缩合剂进行缩合反应，得到N‑芴甲氧羰基–O‑辛酰基‑丝/苏氨酸‑苄酯，经过纯化，将N‑芴甲氧羰基–O‑辛酰基‑丝/苏氨酸‑苄酯加入脱苄基试剂通过钯炭氢化去苄基，得到N‑芴甲氧羰基–O‑辛酰基‑丝/苏氨酸‑苄酯。本发明的产物在多肽药物领域有重要应用。
• 一种N-芴甲氧羰基-3-氯-丙氨酸苄酯的制备方法
  申请人：吉尔生化（上海）有限公司

  公开号：CN112479933A

  公开（公告）日：2021-03-12

  本发明涉及一种N‑芴甲氧羰基‑3‑氯‑丙氨酸苄酯的制备方法，主要解决现有合成方法的反应步骤太长，收率低，产物应用范围狭窄等问题。本发明的技术方案为：一种N‑芴甲氧羰基‑3‑氯‑丙氨酸苄酯的制备方法，包括以下步骤：由N‑芴甲氧羰基‑丝氨酸‑苄酯为起始原料，与氯化试剂在加热条件下在有机溶剂中反应，经后处理得到N‑芴甲氧羰基‑3‑氯‑丙氨酸苄酯。本发明的产物作为一个重要起始物在多肽药物领域有重要应用。
• 一种三价碘试剂参与的糖苷化方法
  申请人：华中科技大学

  公开号：CN116554245A

  公开（公告）日：2023-08-08

  一种三价碘试剂参与的糖苷化方法，其特征在于，糖基供体(I)在三价碘试剂、过渡金属催化剂存在下活化，然后与受体(II)在酸催化下反应或直接反应，得到糖苷化产物(III)；所述糖基供体(I)中，Gly为糖环上一个或多个羟基被保护基保护的糖基；X为氧、硫或硒原子；R为烷基或芳基；所述受体(II)选自含有一个或多个自由羟基的糖类、醇类、酚类、黄酮类、羧酸类、磷酸类、嘧啶类、嘌呤类、酰胺类、磺酰胺类、胍类、芳基胺类、吲哚类、烯醇硅醚类、硫醇或硫酚类亲核试剂。
• Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis
  作者：Yalong Zhang、Saddam M. Muthana、David Farnsworth、Olaf Ludek、Kristie Adams、Joseph J. Barchi、Jeffrey C. Gildersleeve

  DOI：10.1021/ja212188r

  日期：2012.4.11

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.