Fmoc-L/D-Pmp(O-tBu)2-OH | 138228-86-1

• 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: Fmoc-L/D-Pmp(O-tBu)2-OH
• 英文别名: N^αFmoc-(o,o-di-t-butyl)phosphono-p-methylphenylalanine；4-<(di-tert-butylphosphono)methyl>-N-(fluoren-9-ylmethoxycarbonyl)-D,L-phenylalanine；N^α-Fmoc-Pmp(OBu^t)-OH；N-fluoren-9-ylmethoxycarbonyl 4-(di-tert-butylphosphonomethyl)-D,L-phenylalanine；4-[Bis(tert-butyl)phosphonomethyl]-N-Fmoc-DL-phenylalanine；4[Bis(t-butyl)phosphonomethyl]-N-Fmoc-DL-phenylalanine；3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphorylmethyl]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 138228-86-1
• 化学式: C₃₃H₄₀NO₇P
• 分子量: 593.657
• InChiKey: ORTJTEQKISNAEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Fmoc-L/D-Pmp(O-tBu)2-OH 生成 H-Arg-Glu-.Asn-Glu-Pmp-Met-Pro-Met-Ala-Pro-Glu-Ile-His-OH
  参考文献：
  名称：

  Solid-phase synthesis of nonhydrolyzable phosphotyrosyl peptide analogues with Nα-Fmoc-(O,O-di-t-butyl)phosphono-p-methylphenylalanine

  摘要：

  A new, protected derivative of phosphonomethylphenylalanine is used to synthesize nonhydrolyzable analogs of phosphotyrosyl peptides for use as inhibitors and affinity ligands of proteins that recognize phosphotyrosyl sequences.

  DOI：

  10.1016/0040-4039(91)80753-s
• 作为产物：
  描述：

  4-[Bis(tert-butyl)phosphonomethyl]-D,L-phenylalanine methyl ester 、 9-芴基甲基1-苯并三唑基碳酸酯 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醚 、 氯仿 为溶剂， 生成 Fmoc-L/D-Pmp(O-tBu)2-OH
  参考文献：
  名称：

  Phosphonoalkyl phenylalanine compounds suitably protected for use in

  摘要：

  该披露涉及提供含有膦酸衍生物的苯丙氨酸及其光学活性异构体，这些衍生物以一种使它们适合于利用标准固相或溶液相技术轻松地纳入多肽的方式进行官能化。

  公开号：

  US05475129A1

文献信息

• LARGE SCALE PREPARATION OF CELL PERMEABLE, NON-PHOSPHATE-CONTAINING GRB2 SH2 DOMAIN INHIBITORS
  作者：Ding-Guo Liu、Zhu-Jun Yao、Yang Gao、Terrence R. Burke

  DOI：10.1080/00304940009356287

  日期：2000.4

  Inhibitors of cellular signal transduction are emerging as important new therapeutics for several diseases including cancers' and diabetes.' Antagonists of aberrant protein-tyrosine kinasedependent signalling are particularly interesting7 with analogues l4 and 2s representing two noteworthy examples which have been reported recently to potently inhibit Grb2 SH2 domain binding both in extracellular

  细胞信号转导抑制剂正在成为包括癌症和糖尿病在内的多种疾病的重要新疗法。异常蛋白酪氨酸激酶依赖性信号传导的拮抗剂特别令人感兴趣 7，其中类似物 14 和 2s 代表了两个值得注意的例子，最近据报道它们在细胞外测定和全细胞制备中均能有效抑制 Grb2 SH2 结构域结合。Grb2 SH2 结构域在多种癌症（包括乳腺癌和白血病）中发挥的核心作用，使 1 和 2 成为有用的药理学工具和治疗剂的潜在价值。以前 1 和 2 都仅以毫克级制备。然而，由于需要显着更大的数量，本文报道了它们通过适用于相关信号转导抑制剂放大的技术在数百毫克规模上的合成。特别值得注意的是应用径向压缩技术以实现近 1 g 规模的最终产品 HPLC 纯化。
• Application of azide–alkyne cycloaddition ‘click chemistry’ for the synthesis of Grb2 SH2 domain-binding macrocycles
  作者：Won Jun Choi、Zhen-Dan Shi、Karen M. Worthy、Lakshman Bindu、Rajeshri G. Karki、Marc C. Nicklaus、Robert J. Fisher、Terrence R. Burke

  DOI：10.1016/j.bmcl.2006.08.004

  日期：2006.10

  domain-binding assays the monomeric (S)-Pmp-containing macrocycle exhibited a K(d) value of 0.23microM, while the corresponding dimeric macrocycle was found to have greater than 50-fold higher affinity. The open-chain dimer was also found to have affinity equal to the dimeric macrocycle. This work represents the first application of 'click chemistry' to the synthesis of SH2 domain-binding inhibitors and

  铜（I）促进的[3 + 2]叠氮化物与末端炔烃的惠斯根环加成反应被用于基于Grb2 SH2域结合基序“ Pmp-Ac（6）c-Asn”制备含三唑的大环，其中Pmp和Ac（6）c分别代表4-膦酰基甲基苯丙氨酸和1-氨基环己烷羧酸。当在1mM底物浓度下进行环加成反应时，单体单元发生环化。在2mM底物浓度下，主要产物是大环二聚体。在Grb2 SH2域结合测定中，含单体（S）-Pmp的大环化合物的K（d）值为0.23microM，而相应的二聚体大环化合物的亲和力高出50倍以上。还发现开链二聚体的亲和力等于二聚体大环。
• Process of making benzylic .alpha.,.alpha.-diflurophosphonates from
  申请人：The United States of America as represented by the Secretary of the

  公开号：US05264607A1

  公开（公告）日：1993-11-23

  The disclosure is concerned with providing phosphonic acid-containing derivatives of phenylalanine and optically active isomers thereof, which are functionalized in a manner which makes them suitable for facile incorporation into peptides using standard solid-phase or solution-phase techniques. The disclosure is also concerned with providing an advantageous one-step reaction method for preparing benzylic .alpha.,.alpha.-difluorophosphonates from corresponding benzylic ketophosphonates.

  该公开涉及提供含有膦酸衍生物的苯丙氨酸及其光学活性异构体，这些衍生物以一种使它们适合通过标准固相或溶液相技术轻松地纳入肽中的方式进行官能化。该公开还涉及提供一种有利的一步反应方法，用于从相应的苯基酮膦酸酯制备苄基α,α-二氟膦酸酯。
• New synthesis of D,L-fmoc protected 4- phosphonomethylphenylalanine derivatives and their enzymatic resolution
  作者：Krystyna baczko、Wang-Qing Liu、Bernard P. Roques、Christlane Garbay-Jaureguiberry

  DOI：10.1016/0040-4020(95)01003-3

  日期：1996.2

  enzymatic resolution of ethyl 4-[(dimethylphosphono)methyl]-D,L-phenylalaninate succeeded. These results are discussed by comparison with the literature data. The L and D amino acids were used to prepare separately, through solid-phase peptide synthesis, followed by deprotection of dimethylphosphonate group by trimethylsilyliodide (TMSI) in acetonitrile, the L and D isomers of Glu-Asp-Val- Pmp-Glu-Asn-Leu-His-Thr

  描述了适用于固相肽合成的N - Fmoc 4-膦酰基甲基-D，L-苯丙氨酸在二叔丁基或二甲基膦酸酯形式（Fmoc-Pmp（OR）2）保护下的新合成方法。这些O的水解稳定类似物的拆分通过非对映异构体盐的部分重结晶或使用枯草杆菌蛋白酶嘉士伯酯酶尝试了β-磷酸酪氨酸。只有4-[（（二甲基膦酰基）甲基]乙基-D，L-苯丙氨酸乙酯的酶促拆分成功。通过与文献数据进行比较来讨论这些结果。氨基酸的L和d被用来分别制备，通过固相肽合成，接着在乙腈中由三甲基甲dimethylphosphonate基的脱保护（TMSI），GLU-ASP-Val-的L和d异构体PMP -Glu-ASN -Leu-His-Thr，一种肽，对应于磷酸酶PTP 1C的潜在磷酸化位点。
• Preparation of fluoro- and hydroxy-4-(phosphonomethyl)-D,L-phenylalanine suitably protected for solid-phase synthesis of peptides containing hydrolytically stable analogs of O-phosphotyrosine
  作者：Terrence R. Burke、Mark S. Smyth、Motoyoshi Nomizu、Akira Otaka、Peter R. Roller

  DOI：10.1021/jo00058a009

  日期：1993.3

  4-[(Di-tert-butylphosphono)methyl]-N-(fluoren-9-ylmethoxycarbonyl)-D,L-phenylalanine [O-di-tert-butyl-Pmp-N-Fmoc, 3] has previously been shown to be a useful reagent for the solid-phase synthesis of peptides containing the hydrolytically stable O-phosphotyrosyl mimetic, phosphonomethylphenylalanine (Pmp, 2). One potential limitation of Pmp-containing peptides relative to the corresponding phosphotyrosyl prototypes is the higher pK(a2) value of phosphonic acids as compared to that of phosphates. In an effort to prepare Pmp analogues which more closely approximate phosphotyrosyl residues, O-di-tert-butyl-Pmp-N-Fmoc derivatives were made bearing monofluoro (4), difluoro (5), and hydroxy (6) substituents at the phosphonate methylene. The synthetic utility of analogues 4 and 6 was demonstrated by solid-phase synthesis of the hexameric peptide, H-Gly-X-Val-Pro-Met-Leu-OH, where X = monofluoro Pmp and hydroxy Pmp, respectively. These peptides are analogues of the SH2 recognition motif ''phosphoTyr-Val-Pro-Met-Leu'', which is important for mitogenic cellular signal transduction. The hydrolytic lability of difluoro Pmp analogue 5 precluded its usefulness in peptide synthesis. Along with O-di-tert-butyl-Pmp-N-Fmoc (3), monofluoro (4) and hydroxy (6) derivatives may prove to be useful synthons in the preparation of peptides containing hydrolytically stable analogues of phosphotyrosyl residues.