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Chiral alpha-amino acid derivative and preparation method thereof

A technology of chiral amino acids and derivatives, which is applied in the preparation of carbamic acid derivatives, sulfonamides, and organic compounds, and can solve the problems of cumbersome processes, poor applicability, and unsatisfactory catalytic asymmetric synthesis.

Active Publication Date: 2017-11-07
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In other related studies, there are few reports on the efficient synthesis of α-amino acid esters through the enamine pathway catalyzed by small organic molecules.
However, the target product obtained in most researches is often the protecting group of the amino group is still an aryl group, and this aromatic amine structure does not use the application in organic synthesis, and requires a further deprotection / protection process, which makes the process too cumbersome and difficult to apply. poor
In the majority of studies, the direct synthesis of α-amino acid esters was only reported in 2014 by Jocabosen et al., who successfully realized the synthesis of α-amino acid esters through the catalysis of bifunctional catalyst thiourea, but the catalytic The selectivity has not yet met the requirements of catalytic asymmetric synthesis, and the chiral control in the reaction process requires the reaction to be carried out at a lower temperature, which still has great disadvantages

Method used

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  • Chiral alpha-amino acid derivative and preparation method thereof
  • Chiral alpha-amino acid derivative and preparation method thereof
  • Chiral alpha-amino acid derivative and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093] Embodiment 1, N, the preparation of O-acetal

[0094] Method 1: Using CbzNH 2 As the starting material, the target branched chain N, O-acetal compound is obtained through condensation of amine and glyoxylate. The specific synthesis steps are:

[0095] CbzNH 2 (Benzyl carbamate), ethyl glyoxylate are mixed at a molar ratio of 1:1.3, acetic acid and acetic anhydride are mixed at a volume ratio of 1:3 as a reaction solvent, stirred at 60°C for 1 day, and unreacted Acetic anhydride and acetic acid can obtain the corresponding stable branched chain Cbz protected amino N, O-acetal compound, the specific reaction equation is as figure 2 shown;

[0096] Method 2: Realized by step-by-step synthesis, first through CbzNH 2 Condensation with glyoxylic acid ester to obtain N, O hemiacetal, and then protect the hydroxyl group with a protecting group, and then obtain the raw material of N, O acetal. The specific method includes the following process steps:

[0097] CbzNH 2 (Benz...

Embodiment 2

[0100] Embodiment 2, N, the preparation of O-acetal

[0101] CbzNH 2 (Benzyl carbamate) and chloral were mixed at a molar ratio of 1:1.3, reacted in ethyl acetate at 60°C for 1 day, and the solvent was removed by rotary evaporation to obtain solid N,O hemiacetal, and then added 5 Molar equivalent of acetic anhydride, 1% molar equivalent of pyridine, react at 25°C for 1 day, remove unreacted acetic anhydride, and obtain branched N,O-acetal compound of Cbz protected amino group, specific reaction equation Such as image 3 shown.

[0102]

[0103] The structure is confirmed as follows: 1 H NMR (400MHz, CDCl 3 )δ7.37(s,5H),6.93(d,J=10.0Hz,1H),5.69(s,1H),5.19(s,2H),2.17(s,3H). 13 C NMR (101MHz, CDCl 3 )δ168.16, 135.51, 128.80, 128.72, 128.53, 98.21, 81.38, 68.26, 20.69.

Embodiment 3

[0104] Embodiment 3, N, the preparation of O-acetal

[0105] CbzNH 2 (Benzyl carbamate), mixed trifluoroacetaldehyde hydrate at a molar ratio of 1:1.3, reacted in ethyl acetate at 60°C for 1 day, and removed the solvent by rotary evaporation to obtain solid N, O hemiacetal, and then added 5 molar equivalents of acetic anhydride, 1% molar equivalents of pyridine, react at 25°C for 1 day, remove unreacted acetic anhydride, and obtain branched N,O-acetal compounds of Cbz protected amino groups, specific reactions Equation such as image 3 shown.

[0106]

[0107] The structure is confirmed as follows: 1 H NMR (500MHz, CDCl 3 )δ7.35(q, J=15.0Hz, 5H), 6.80(s, 1H), 5.66(d, J=9.0Hz, 1H), 5.17(d, J=12.0Hz, 2H), 2.14(s, 3H). 13 C NMR (126MHz, CDCl 3 )δ168.09, 154.27, 135.26, 128.79, 128.75, 128.53, 128.47, 122.80, 120.57, 72.72, 72.43, 72.14, 71.85, 68.32, 20.52.

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PUM

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Abstract

The invention discloses a chiral alpha-amino acid derivative and a preparation method thereof. The structural formula of the chiral alpha-amino acid derivative disclosed by the invention is of formula I shown in the specification. The preparation method of the derivative comprises the following steps: mixing a carbonyl compound with a N,O-acetal mixture, a chiral primary tert-diamine organic small molecule catalyst, strong acid and weak acid, and performing a reaction, thereby obtaining the chiral alpha-amino acid derivative. The chiral alpha-amino acid derivative comprises aldehyde and / or ketone. The chiral alpha-amino acid derivative disclosed by the invention is prepared under catalysis of the chiral primary tert-diamine organic small molecule catalyst of a simple structure via one-step synthesis without solvent, thus being simple and efficient.

Description

technical field [0001] The invention relates to a chiral α-amino acid derivative and a preparation method thereof, belonging to the technical field of organic synthesis. Background technique [0002] At the beginning of the 20th century, Mannich et al. reported the first Mannich reaction, which realized the functionalization process of the α-position of N. Subsequently, the report and application of the Mannich reaction were widely developed, and the report on the application of asymmetric methods was not until 1997. Achieved by Kobayashi through a chiral Zr catalyst. The application of Mannich reaction to realize the construction of chiral skeleton has been further developed, and the construction of amino acid skeleton at α-position and β-position directly through Mannich reaction is also a new synthetic method. [0003] The chiral amino acid structure has a very wide range of applications, and can be applied to the synthesis of ligands in organic synthesis and the design ...

Claims

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Application Information

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IPC IPC(8): C07C271/22C07C271/16C07C311/09C07C269/00C07C303/40
CPCC07C271/22C07B2200/07C07C271/16C07C311/09
Inventor 罗三中尤扬恩张龙
Owner INST OF CHEM CHINESE ACAD OF SCI
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