methyl 4-<(di-tert-butylphosphono)difluoromethyl>-N-(benzyloxycarbonyl)-D,L-phenylalaninate | 146745-48-4

• 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: methyl 4-<(di-tert-butylphosphono)difluoromethyl>-N-(benzyloxycarbonyl)-D,L-phenylalaninate
• 英文别名: Methyl 4-[bis(tert-butoxy)phosphoryldifluoromethyl]-N-(benzyloxycarbonyl)-D,L-phenylalaninate；methyl 3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl-difluoromethyl]phenyl]-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 146745-48-4
• 化学式: C₂₇H₃₆F₂NO₇P
• 分子量: 555.556
• InChiKey: WPXUQJIHTXQMBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 4-<(di-tert-butylphosphono)difluoromethyl>-N-(benzyloxycarbonyl)-D,L-phenylalaninate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以40%的产率得到methyl 4-<(di-tert-butylphosphono)difluoromethyl>-D,L-phenylalaninate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jo00058a009
• 作为产物：
  描述：

  双(1,1-二甲基乙基)[[4-(二乙氧基甲基)苯基]羟甲基]膦酸酯 在 palladium on activated charcoal 盐酸 、 重铬酸吡啶 、 二乙胺基三氟化硫 、 4 A molecular sieve 、 Celite 、 氢气 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， -78.0~25.0 ℃ 、275.79 kPa 条件下， 反应 8.41h， 生成 methyl 4-<(di-tert-butylphosphono)difluoromethyl>-N-(benzyloxycarbonyl)-D,L-phenylalaninate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jo00058a009

文献信息

• Phosphonoalkyl phenylalanine compounds suitably protected for use in
  申请人：The United States of America as represented by the Department of Health

  公开号：US05475129A1

  公开（公告）日：1995-12-12

  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.

  本公开涉及提供含磷酸基的苯丙氨酸衍生物及其光学活性异构体，它们以一种使其适合于使用标准固相或溶液相技术轻松地纳入肽中的方式进行了功能化。
• 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.

  本公开涉及提供含有磷酸基的苯丙氨酸衍生物及其手性活性异构体，它们以一种使它们适合使用标准固相或溶液相技术容易地纳入肽中的方式进行官能化。本公开还涉及提供一种优越的一步反应方法，用于从相应的苄基酮磷酸酯制备苄基α，α-二氟磷酸酯。
• US5264607A
  申请人：——

  公开号：US5264607A

  公开（公告）日：1993-11-23
• US5475129A
  申请人：——

  公开号：US5475129A

  公开（公告）日：1995-12-12
• [EN] PHOSPHONOALKYL PHENYLALANINE COMPOUNDS SUITABLY PROTECTED FOR USE IN PEPTIDE SYNTHESIS<br/>[FR] COMPOSES DE PHOSPHONOALKYLE PHENYLALANINE PROTEGES DE MANIERE APPROPRIEE UTILISABLES DANS LA SYNTHESE PEPTIDIQUE
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：WO1993025561A1

  公开（公告）日：1993-12-23

  (EN) 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.(FR) Dérivés contenant de l'acide phosphonique issus de la phénylalanine et de ses isomères optiquement actifs. Ces dérivés sont fonctionnalisés de manière à pouvoir être incorporés facilement dans des peptides à l'aide de techniques standard en phase solide ou en solution.