(4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-4-甲基-1-氧代戊基]-2,2-二甲基-4-恶唑烷羧酸 | 339531-50-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物
• 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
• 中文名称: (4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-4-甲基-1-氧代戊基]-2,2-二甲基-4-恶唑烷羧酸
• 英文名称: Fmoc-Leu-Ser(Ψ^Me,Mepro)-OH
• 英文别名: Fmoc-Leu-Ser-(ψMe,MePro)-OH；Fmoc-Leu-Ser(Psi(Me,Me)Pro)-OH；(4S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentanoyl]-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid
• CAS: 339531-50-9
• 化学式: C₂₇H₃₂N₂O₆
• 分子量: 480.561
• InChiKey: BUYLKVIICSUHDX-GOTSBHOMSA-N

物化性质

• 沸点：
  695.1±55.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• WGK Germany：
  2

制备方法与用途

生物活性方面，Fmoc-Leu-Ser(psi(Me,Me)pro)-OH 是一种二肽。

反应信息

• 作为反应物：
  描述：

  (4S)-3-[(2S)-2-[[芴甲氧羰基]氨基]-4-甲基-1-氧代戊基]-2,2-二甲基-4-恶唑烷羧酸 在 trityl chloride polystyrene resin 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以125 mg的产率得到NH2-Leu-Ser(ψ-^Me,Mepro)-Leu-Ser(ψ-^Me,Mepro)-OH
  参考文献：
  名称：

  Synthesis of All-l Cyclic Tetrapeptides Using Pseudoprolines as Removable Turn Inducers

  摘要：

  Cyclic tetrapeptides h we generated great interest because of their broad-ranging biological properties. In order to synthesize these highly strained 12-membered cyclic compounds, a cyclization strategy using pseudoprolines as removable turn inducers has been developed. The pseudoproline derivatives induce a cisoid amide bond in the linear peptide backbone which facilitates cyclization. After cyclization, the turn inducers can be readily removed to afford cyclic tetrapeptides containing serine or threonine residues.

  DOI：

  10.1021/ol101018w

文献信息

• Solid‐Phase Thiol–Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist
  作者：Elyse T. Williams、Paul W. R. Harris、Muhammad A. Jamaluddin、Kerry M. Loomes、Debbie L. Hay、Margaret A. Brimble

  DOI：10.1002/anie.201805208

  日期：2018.9.3

  We report a new method herein coined SP‐CLipPA (solid‐phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono‐S‐lipidated peptides. This technique utilizes thiol–ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin‐bound peptide. Advantages of SP‐CLipPA include: ease of handling, conversions of up to 91 %, by‐product removal by simple filtration

  我们在此报告了一种新的合成SP-CLipPA（肽或氨基酸的固相半胱氨酸脂质化）的方法，用于合成单S脂化肽。该技术利用硫醇-烯化学方法将乙烯基酯与半保护的树脂结合肽的游离硫醇结合。SP‐CLipPA的优势包括：易于处理，高达91％的转化率，可通过简单过滤除去副产物以及单个纯化步骤。此外，所需的脂化产品显示出与杂质的高色谱分离度，从而促进了RP-HPLC的纯化。为了展示SP‐CLipPA的实用性，我们合成了一种有效的降钙素基因相关肽（CGRP）受体拮抗剂肽，具有出色的收率和纯度。该肽选自一系列CGRP 8–37和CGRP的脂化类似物7-37岁，具有治疗偏头痛的潜力。
• [EN] PEPTIDE CONJUGATE CGRP RECEPTOR ANTAGONISTS AND METHODS OF PREPARATION AND USES THEREOF<br/>[FR] CONJUGUÉS PEPTIDIQUES À TITRE D'ANTAGONISTES DU RÉCEPTEUR CGRP, LEURS PROCÉDÉS DE PRÉPARATION ET LEURS UTILISATIONS
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2019087161A1

  公开（公告）日：2019-05-09

  Disclosed are peptide conjugates that are calcitonin gene-related peptide (CGRP) receptor antagonists comprising a CGRP peptide, wherein at least one amino acid of the peptide is covalently conjugated to a lipid-containing moiety. Also disclosed are pharmaceutical compositions and kits comprising such conjugates, methods of preparing such conjugates, and uses of such antagonists.

  披露了肽共轭物，它们是降钙素基因相关肽（CGRP）受体拮抗剂，包括一个CGRP肽，其中肽的至少一个氨基酸以共价结合的方式与含脂肪的基团结合。还披露了包含这种共轭物的药物组合物和试剂盒，制备这种共轭物的方法，以及这种拮抗剂的用途。
• INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES
  申请人：Corden Pharma Colorado, Inc.

  公开号：EP2205624B1

  公开（公告）日：2016-09-07
• Insulinotropic peptide synthesis using solid and solution phase combination techniques
  申请人：King Barry Thomas

  公开号：US20090149628A1

  公开（公告）日：2009-06-11

  The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to one of the fragments. The fragments are then coupled together in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to other fragments. The present invention is very useful for forming insulinotropic peptides such as Exenatide(1-39) and its natural and non-natural counterparts.
• PEPTIDE CONJUGATE CGRP RECEPTOR ANTAGONISTS AND METHODS OF PREPARATION AND USES THEREOF
  申请人：Auckland UniServices Limited

  公开号：US20200353088A1

  公开（公告）日：2020-11-12

  Disclosed are peptide conjugates that are calcitonin gene-related peptide (CGRP) receptor antagonists comprising a CGRP peptide, wherein at least one amino acid of the peptide is covalently conjugated to a lipid-containing moiety. Also disclosed are pharmaceutical compositions and kits comprising such conjugates, methods of preparing such conjugates, and uses of such antagonists.