多西他赛杂质44 | 147058-27-3

• 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: 多西他赛杂质44
• 中文别名: 多西他赛杂质46
• 英文名称: methyl (2R,3S)-2-hydroxy-3-[(S)-α-methylbenzylamino]-3-phenylpropionate
• 英文别名: methyl (2R,3S)-2-hydroxy-3-phenyl-3-<(S)-1-methylbenzylamino>propanoate；(2R,3S)-2-hydroxy-3-phenyl-3-(((S)-1-phenethyl)amino)propionic acid methyl ester；methyl (2R,3S)-2-hydroxy-3-phenyl-3-[(S)-1-phenylethylamino]propionate；methyl (2R,3S)-2-hydroxy-3-[(S)-1-phenyl]ethylamino-3-phenylpropionate；methyl (2R,3S)-2-hydroxy-3-[1-(S)-phenyl]ethylamino-3-phenylpropionate；methyl (2R,3S)-2-hydroxy-3-phenyl-3-[[(1S)-1-phenylethyl]amino]propanoate
• CAS: 147058-27-3
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: CCUHNAGNTZGTTF-RRQGHBQHSA-N

物化性质

• 沸点：
  444.6±45.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  多西他赛杂质44 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 4-甲基苯磺酸吡啶 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 为溶剂， 20.0~80.0 ℃ 、2.38 MPa 条件下， 反应 78.0h， 生成 (4S,5R)-2,2-二甲基-4-苯基-3-叔丁氧基羰基-3,5-氧氮杂环戊烷甲酸
  参考文献：
  名称：

  A practical access to chiral phenylisoserinates, preparation of Taxotere® analogs

  摘要：

  A practical diastereoselective synthesis of phenylisoserine methyl esters 8a-c is described using alpha-methyl-benzylamine as the chiral template of a Staudinger reaction. Optically pure diastereoisomers 6a-c were easily recovered by crystallization. After opening of these intermediate azetidinones by hydrochloric acid and methanol, regioselective cleavage of the chiral auxiliary was achieved by hydrogenation over palladium. Phenylisoserinates 8b,c were used to prepare analogs of Taxotere(R).

  DOI：

  10.1016/s0040-4039(00)61724-0
• 作为产物：
  描述：

  [(3S,4R)-2-oxo-4-phenyl-1-[(1S)-1-phenylethyl]azetidin-3-yl] acetate 在 盐酸 、 氢氧化钾 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 多西他赛杂质44
  参考文献：
  名称：

  A practical access to chiral phenylisoserinates, preparation of Taxotere® analogs

  摘要：

  A practical diastereoselective synthesis of phenylisoserine methyl esters 8a-c is described using alpha-methyl-benzylamine as the chiral template of a Staudinger reaction. Optically pure diastereoisomers 6a-c were easily recovered by crystallization. After opening of these intermediate azetidinones by hydrochloric acid and methanol, regioselective cleavage of the chiral auxiliary was achieved by hydrogenation over palladium. Phenylisoserinates 8b,c were used to prepare analogs of Taxotere(R).

  DOI：

  10.1016/s0040-4039(00)61724-0

文献信息

• A Highly Diastereoselective Synthesis of α-Hydroxy-β-amino Acid Derivatives via a Lewis Acid Catalyzed Three-Component Condensation Reaction
  作者：Federico Gassa、Alessandro Contini、Gabriele Fontana、Sara Pellegrino、Maria Luisa Gelmi

  DOI：10.1021/jo1011762

  日期：2010.11.5

  A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley’s lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection

  一系列的非常高效的三组分合成顺式α羟基-β氨基酯，在高diastereoselection和产率获得，实现了由醛，苄胺，和从莱伊的内酯衍生的乙烯酮甲硅烷基缩醛开始。优化了合成方案，无需分离中间体即可获得上述化合物。通过关键反应步骤的计算模型研究了观察到的非立体定向的起源。
• Process for the preparation of .beta.-phenylisoserine and .beta.-lactam
  申请人：Rhone-Poulence Rorer S.A.

  公开号：US05939561A1

  公开（公告）日：1999-08-17

  The present invention relates to new process for the preparation of .beta.-phenylisoserine and its analogues of general formula: ##STR1## which are particularly useful for preparing taxane derivatives which have remarkable antitumour and antileukaemic activities.

  本发明涉及一种新的制备β-苯基异丝氨酸及其类似物的方法，其一般化学式如下：##STR1## 这些化合物特别适用于制备具有显著抗肿瘤和抗白血病活性的紫杉醇衍生物。
• Process for the preparation of .beta.-phenylisoserine and its analogues
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05608102A1

  公开（公告）日：1997-03-04

  This invention relates to a method for preparing .beta.-phenylisoserine and analogues thereof having general formula (I) ##STR1## from an aromatic aldehyde and an .alpha.-methylarylamine-S, and through a lactam of general formula (II) as described herein. The acids of general formula (I) (R.dbd.H) may be used to prepare taxane derivatives having remarkable antitumoral and antileukaemic activity.

  这项发明涉及一种制备β-苯基异丝氨酸及其类似物的方法，其通式为(I)。从芳香醛和α-甲基芳基胺-S，以及本文所述的通式(II)的内酰胺中制备。通式(I)中的酸(R=H)可用于制备具有显著抗肿瘤和抗白血病活性的紫杉醇衍生物。
• 一种多西紫杉醇侧链的合成方法
  申请人：重庆市碚圣医药科技股份有限公司

  公开号：CN112574134A

  公开（公告）日：2021-03-30

  一种多西紫杉醇侧链的合成方法，以(2R，3S)‑2‑羟基‑3‑苯基‑3‑(((S)‑1‑苯乙基)氨基)丙酸甲酯为原料，在钯碳、氢气的参与下发生还原反应，得到(2R，3S)‑3‑苯基异丝氨酸甲酯盐，再通过二碳酸二叔丁酯取代反应制得(2R，3S)‑3‑叔丁氧羰基‑2‑羟基‑3‑苯基丙酸甲酯，接着通过环化保护反应制得(4S，5R)‑3‑叔丁氧羰基‑2‑(4‑甲氧基苯基)‑4‑苯基‑5‑噁唑啉羧酸甲酯，最后通过水解得到多西紫杉醇侧链粗品，多西紫杉醇侧链粗品通过重结晶进一步纯化后得到多西紫杉醇侧链成品。本发明合成方法是一种安全环保、经济、高效、适宜大规模工业化生产的合成方法。
• Method for the preparation of .beta.-phenylisoserine derivatives
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05681970A1

  公开（公告）日：1997-10-28

  Method for the preparation of .beta.-phenylisoserine derivatives of general formula (I) involving the action of an anhydride and hydrogen with a product of general formula (II). The products of general formula (I) are especially useful in the preparation of taxoids having outstanding antitumour properties. In general formulae (I) and (II), Ar is an aryl radical, Ph is a phenyl radical or an optionally substituted .alpha. or .beta.-naphtyl, R is a hydrogen atom or an alkyl radical optionally substituted by a phenyl radical and R.sub.1 is an optionally substituted phenyl radical or a R.sub.2 --O radical wherein R.sub.2 is an alkyl, alkenyl, cycloalkyl, phenyl or heterocyclyl. ##STR1##

  一种制备β-苯基异丝氨酸衍生物的方法，包括使用酸酐和氢与通式（II）的产物作用。通式（I）的产物在制备具有出色抗肿瘤性能的紫杉醇中特别有用。在通式（I）和（II）中，Ar是芳基基团，Ph是苯基基团或可选择取代的α或β-萘基基团，R是氢原子或可选择取代苯基的烷基基团，R1是可选择取代的苯基基团或R2-O基团，其中R2是烷基，烯基，环烷基，苯基或杂环基。