CN109762034B

CN109762034B - Preparation method of novel terephthalaldehyde D-glucosamine Schiff base

Info

Publication number: CN109762034B
Application number: CN201910134408.0A
Authority: CN
Inventors: 韩志钟; 翁清花; 方玉婵; 易锦泉; 陈程云; 康杰
Original assignee: Fujian Medical University
Current assignee: Fujian Medical University
Priority date: 2019-02-23
Filing date: 2019-02-23
Publication date: 2022-04-29
Anticipated expiration: 2039-02-23
Also published as: CN109762034A

Abstract

The invention discloses a preparation method of novel p-terephthalaldehyde D-glucosamine Schiff base, which comprises the following steps: weighing D-glucosamine hydrochloride, putting the D-glucosamine hydrochloride into a beaker, adding anhydrous methanol, adding sodium hydroxide for reaction, filtering to remove NaCl, slowly dropwise adding an anhydrous methanol solution of terephthalaldehyde into the filtrate, reacting at the temperature of 35 ℃ in a water bath, cooling, standing overnight, separating out solid powder, filtering, washing for a plurality of times by using cold anhydrous methanol, and performing vacuum drying to obtain terephthalaldehyde D-glucosamine Schiff base; the compound has good water solubility, good optical performance and certain bacteriostatic activity. The compound can be used as a fluorescent probe for tumor cell imaging, and is expected to expand the application range of Schiff base fluorescent dyes.

Description

Preparation method of novel terephthalaldehyde D-glucosamine Schiff base

Technical Field

The invention belongs to the field of synthesis and preparation of Schiff bases, and particularly relates to synthesis and preparation methods of two novel p-terephthalaldehyde D-glucosamine Schiff bases.

Background

Schiff base is synthesized into a compound containing imino (-C = N-) by Hugo Schiff with salicylaldehyde, aniline and copper ions for the first time. The Schiff base is a compound containing amino (-NH)₂and-NH-) and aldehyde group (-CHO) to produce organic compound containing imino group or imino group. Different groups can be introduced into the Schiff base structure through different reactants, and the Schiff base has different functions due to the various groups. The Schiff base and the complex thereof have good activities of resisting tumor, bacteria, oxidation, virus and the like, have good application prospects in the fields of chemical catalysis, biomedicine, functional materials, food industry and the like, and play an important role in the electrochemical field.

D-glucosamine is a natural amino monosaccharide, is distributed in almost all tissues of the human body, particularly in articular cartilage, is involved in the construction of human tissues and cell membranes, and is an intermediate substance in the synthesis of protein macromolecules. The D-glucosamine has various biological activities, has good killing effect on tumor cancer cells, and has little toxicity on normal cells of a human body. The D-glucosamine has a plurality of reaction centers in a molecule, amino can be subjected to condensation reaction with an aldehyde compound to prepare Schiff base, and saccharides are introduced into the Schiff base and a metal complex structure thereof, so that a drug with low toxicity and good anticancer activity is expected to be obtained; and the glucose contains a plurality of hydroxyl groups, so that the synthesized Schiff base has good water solubility.

The invention adopts the reaction of terephthalaldehyde and D-glucosamine to successfully synthesize two novel terephthalaldehyde D-glucosamine Schiff bases, and performs the research of performance characterization and bacteriostatic activity.

Disclosure of Invention

The invention aims to provide two novel terephthalaldehyde D-glucosamine Schiff bases and a synthesis method thereof. The Schiff base synthesized by the method has a certain bacteriostatic action, has an autofluorescence effect, and has application prospects in the fields of biology, medicines and the like.

In order to achieve the purpose, the invention adopts the following technical scheme:

a preparation method of novel terephthalaldehyde D-glucosamine Schiff base comprises the following steps: weighing 2.5mmol of D-glucosamine hydrochloride, placing into a beaker, adding 15mL of anhydrous methanol, adding 2.5mmol of sodium hydroxide, reacting for 5min, filtering to remove NaCl, slowly dropwise adding anhydrous methanol solution containing 2.5mmol of terephthalaldehyde into the filtrate, reacting for 50min in a water bath at 35 ℃, cooling, standing overnight, separating out solid powder, filtering, washing with cold anhydrous methanol for several times, and vacuum drying to obtain a compound L₁。

A preparation method of novel terephthalaldehyde D-glucosamine Schiff base comprises the following steps: weighing 2.5mmol of D-glucosamine hydrochloride, placing into a beaker, adding 15mL of anhydrous methanol, adding 2.5mmol of sodium hydroxide, reacting for 5min, filtering to remove NaCl, slowly dropwise adding anhydrous methanol solution containing 1.0mmol of terephthalaldehyde into the filtrate, reacting for 50min in a water bath at 35 ℃, cooling, standing overnight, separating out solid powder, filtering, washing with cold anhydrous methanol for several times, and vacuum drying to obtain a compound L₂。

Specifically, the invention adopts the following technical scheme: the molecular structural formulas of the two novel Schiff bases are respectively as follows: c₁₄H₁₇O₆N（L₁) And C₂₀H₂₈O₁₀N₂（L₂) The preparation method comprises the following specific steps: weighing 2.5mmol of D-glucosamine hydrochloride, placing into a beaker, adding 15mL of anhydrous methanol, adding 2.5mmol of sodium hydroxide, reacting for 5min, filtering to remove NaCl, slowly dropwise adding 2.5mmol of terephthalaldehyde anhydrous methanol solution into the filtrate, reacting for 50min in a water bath at 35 ℃, cooling, standing overnight, separating out solid powder, filtering, washing with cold anhydrous methanol for several times, and vacuum drying to obtain a compound L₁. Compound L₂Method for synthesizing and L₁Similarly, the amount of terephthalaldehyde added was changed to 1 mmol, and the rest was the same.

The invention has the following remarkable advantages: a novel p-terephthalaldehyde D-glucosamine asymmetric Schiff base and a symmetric bis-Schiff base are designed and synthesized, and the compound has good water solubility, good optical performance and certain bacteriostatic activity. The compound can be used as a fluorescent probe for tumor cell imaging, is expected to expand the application range of Schiff base fluorescent dyes, and has important significance for the research of the fluorescent probe.

Drawings

FIG. 1 is a scheme showing the synthesis of terephthalaldehyde D-glucosamine Schiff base;

FIG. 2 is Compound L₁And L₂Schematic structural comparison of (1);

FIG. 3 is Compound L₁And L₂Ultraviolet-visible absorption spectrum of;

FIG. 4 is Compound L₁And L₂(ii) a fluorescence emission spectrum of;

FIG. 5 is Compound L₁And L₂(ii) an infrared spectrum;

FIG. 6 is Compound L₁Is/are as follows¹³C-NMR；

FIG. 7 is Compound L₁Is/are as follows¹H-NMR；

FIG. 8 is Compound L₂Is/are as follows¹³C-NMR；

FIG. 9 is Compound L₂Is/are as follows¹H-NMR。

Detailed Description

The invention is described in detail below with reference to the following figures and examples:

as shown in fig. 1, a synthetic route diagram introduces: weighing 2.5mmol of D-glucosamine hydrochloride, placing into a beaker, adding 10 mL of anhydrous methanol, adding 2.5mmol of sodium hydroxide, reacting for 5min, filtering to remove NaCl, slowly dropwise adding 10 mL of anhydrous methanol solution dissolved with 2.5mmol of terephthalaldehyde into the filtrate, reacting for 50min in a water bath at 35 ℃, cooling, standing overnight, precipitating solid powder, filtering, washing with cold anhydrous methanolWashing for several times and vacuum drying to obtain compound L₁. Compound L₂Method for synthesizing and L₁Similarly, the amount of terephthalaldehyde added was changed to 1 mmol, and the rest was the same. FIG. 2 shows the structural schematic of two novel compounds, L₁And L₂Are novel p-terephthalaldehyde D-glucosamine asymmetric Schiff base and symmetric bis-Schiff base respectively.

(II) ultraviolet spectrum characterization: determination of glucosamine Schiff base L at room temperature₁And L₂Ultraviolet visible absorption spectrum in anhydrous methanol. It can be seen from fig. 3 that the spectra of the two synthesized schiff bases are similar, and the strong absorption peak at 200 nm is caused by N → pi transition of C = N double bond connected with sugar ring; absorption peak of aromatic aldehyde_maxGenerally, about 250 nm, the C = N double bond of the Schiff base and the benzene ring form a larger conjugated pi-electron system, so that the absorption peak generates red shift. Schiff base L₁And L₂λ of_maxAt 251 nm, 270 nm and 278 nm, respectively, the absorption peaks can be attributed to different n → pi, pi → pi transitions.

(III) fluorescence spectrum characterization: the fluorescence emission spectrum of Schiff base in anhydrous methanol (see FIG. 4) was measured at room temperature, with excitation wavelength of 243 nm. The synthesized Schiff base molecule contains a pi electron conjugated system and a benzene ring with a rigid planar structure, so the synthesized Schiff base molecule can emit fluorescence. From the above fluorescence spectrum, it is seen that the substituents attached to the benzene ring are different, resulting in fluorescence wavelength and fluorescence intensity, but the fluorescence spectra are very similar due to the similar structures.

(iv) fourier transform infrared spectroscopy characterization (FT-IR): and (3) carrying out surface organic functional group analysis on the synthesized Schiff base compound by a Fourier transform infrared spectrometer. Taking a proper amount of dry sample powder to be tested and KBr (spectrally pure SP) to be uniformly ground in an agate mortar, tabletting and testing. Glucosamine schiff base compound L₁And L₂The IR spectrum is shown in FIG. 5 and Table 1. Characteristic absorption peaks of C = N double bonds appear in infrared spectra, and characteristic absorption peaks of sugar rings and benzene rings appear simultaneously, which indicates that Schiff bases are formed.With a compound L₁The infrared absorption spectrum analysis of (1) is exemplified by: since glucosamine has a plurality of hydroxyl groups on the molecule, the concentration is 3455 cm^-1A strong and wide stretching vibration absorption peak appears at 1640 cm^-1The characteristic absorption peak of C = N appears, and is 1084 cm^-1The characteristic absorption peak of the pyranyl ether group is 1578 cm^-1、1477 cm^-1、1453 cm^-1The stretching vibration peak of the benzene ring skeleton appears. At 589 cm^-1、563 cm^-1And 549 cm^-1Where the pyranose backbone vibrates. Compound L₁Has an infrared spectrum of 1689 cm^-1A characteristic absorption peak of-CHO appears, and the compound L₂The peak of aldehyde groups disappeared, demonstrating that both aldehyde groups of terephthalaldehyde were replaced, and also laterally evidencing compound L₂And (4) generating.

TABLE 1 Compound L₁And L₂Infrared spectrum data comparison

All units are cm^-1。

And (V) nuclear magnetic carbon spectrum and hydrogen spectrum analysis: and carrying out structural characterization on the synthesized Schiff base compound by nuclear magnetic resonance spectrum NMR (figures 6-9). And (3) respectively measuring the nuclear magnetic resonance carbon spectrum and the hydrogen spectrum of the Schiff base compound by using deuterated DMSO as a solvent (see tables 2-3).

First, L₁And L₂The nuclear magnetic carbon spectrum and the hydrogen spectrum of the Schiff base are pure and have no impurity peak, which indicates that the synthesized Schiff base has high purity. L is₁And L₂The nuclear magnetic resonance carbon spectrum of the Schiff base has characteristic absorption peaks of-C = N-which are respectively positioned at 161.79 ppm and 162.13 ppm, which indicates that the Schiff base is successfully synthesized; and relative to L₂Carbon spectrum of, L₁the-CHO characteristic absorption peak at 193.40 ppm in (A) indicates that only one aldehyde group is substituted for L₁The synthesis is successful. L is₁And L₂Also appears characteristic peaks of-C = N-, located at 8.32 and 8.25 ppm, respectively; l is₂Does not appear in the hydrogen spectrum of-CHO characteristic absorption Peak, indicating Compound L₂In which there is no L₁In addition, the result of integration of the hydrogen spectrum shows the correlation with L₁The number of H in the structure corresponds to the structural formula, so that the compound L can be proved₁Also has no L₂Is present.

TABLE 2 Compound L₁And L₂Comparison of nuclear magnetic resonance carbon spectral data

TABLE 3 comparison of NMR Hydrogen spectra data for Compounds L1 and L2

Compound (I)	Hydrogen spectrum of nuclear magnetic resonanceδ/ppm
			¹H-NMR (500 MHz, DMSO-d ₆)
L₁	2.91 (t, 1H, CH₂) 3.18-3.49 (m, 4H, sugar ring), 3.70-3.78 (m, 1H, CH)₂)，4.62 (t, 1H, OH)，4.78 (t, 1H, OH)，4.98（d, 1H, CH-N），5.04 (d, 1H, OH)，6.67 (d, 1H, OH)，7.99 (s, 4H, ArH)，8.32 (s, 1H, - CH=N-)，10.07 (s, 1H，-CHO)
		L₂	2.93~2.84 (m, 1H, CH₂) 3.17 to 3.54 (m, 4H, sugar ring), 3.70 to 3.78 (ddd, 1H, CH)₂)，4.59 (t, 1H, OH)， 4.75 (t, 1H, OH)，4.92（d, 2H, CH-N），4.98 (d, 1H, OH)，6.62 (d, 1H, OH)，7.83 (s, 2H, ArH)，8.25 (s, 1H, -CH=N-)

(VI) research on bacteriostatic activity

The bacteriostatic activity of the drug was studied by 96-well plate titer assay. The specific process is as follows:

1. and (3) resuscitation: the Escherichia coli is recovered one day before experimentPerforming amplification culture on the next day, and performing experiment when OD 600 nm reaches 0.6 (logarithmic growth phase); drug concentration dilution: drug dilution is carried out by LB culture medium-2 times dilution method; plate 3: uniformly planting escherichia coli liquid reaching logarithmic phase into a 96-well plate by 100 mu L per hole; and 4, dosing: the prepared compound L₁And L₂The drug of (4) was added to a 96-well plate at 100. mu.L per well. Culturing at 5.37 deg.C for 24 hr, and measuring OD 600 nm.

Coli inhibition activity test was performed on two compounds, wherein, when 0.5 mg of the drug was used, compound L₁And L₂The inhibition rate of (A) is more than 80%. The results show that Compound L₁And L₂All have certain bacteriostatic effect.

Claims

1. P-terephthalaldehyde D-glucosamine symmetric bis-Schiff base L₂The preparation method of (A), the L₂The structural formula is as follows:

r is:

，

the method comprises the following steps: weighing 2.5mmol of D-glucosamine hydrochloride, placing into a beaker, adding 15mL of anhydrous methanol, adding 2.5mmol of sodium hydroxide, reacting for 5min, filtering to remove NaCl, slowly dropwise adding anhydrous methanol solution containing 1.0mmol of terephthalaldehyde into the filtrate, reacting for 50min under the condition of 35 ℃ water bath, cooling, standing overnight, separating out solid powder, filtering, washing with cold anhydrous methanol for several times, and vacuum drying to obtain p-terephthalaldehyde D-glucosamine symmetric bis-Schiff base L₂。