CN103030761A - New member in cucurbituril family, namely hinged cucurbit (14) uril and synthesis and separation method thereof - Google Patents

Abstract

The new member of the cucurbit ring family of the present invention-spliced fourteen-membered cucurbit ring and its synthesis and separation method belongs to new organic macrocyclic compounds and its synthesis and separation method. The compound consists of 14 glycoside urea monomers (C ₄ H ₆ N ₄ O ₂ ) Through 28 methylene (-CH ₂ -) bridges to form a folded "8"-shaped cage compound, the general chemical composition formula is: C ₈₄ H ₈₄ N ₅₆ O ₂₈ , the molecular weight is 2324; it is a white crystal , easily soluble in water and polar organic solvents, the compound is spliced with fourteen-membered cucurbit rings (tQ[14]) through (fluorine spectrum, carbon spectrum), mass spectrometry, single crystal structure analysis, etc. to confirm it accurately, the compound Synthesized by the traditional melon ring synthesis method, and then separated by column chromatography.

Description

A new member of the melon ring family—spliced fourteen-membered melon ring and its synthesis and separation method

technical field

The present invention relates to a novel macrocyclic compound and its synthesis and separation methods. Specifically, it is a new member of the melon ring family—spliced fourteen-membered melon ring and its synthesis and separation method.

Background technique:

In 1981, the Mock research group characterized the first member of the cucurbit ring family - the six-membered cucurbit ring (Q[6]) by single crystal X-ray diffraction method. In 2000, the Day research group and Kim research group simultaneously reported three The homologues of the six-membered melon ring—the five-membered melon ring (Q[5]), the seven-membered melon ring (Q[7]) and the eight-membered melon ring (Q[8]); in 2002, the Day research group reported that the package A ten-membered melon ring with a five-membered melon ring (Q[5]Q[10]); American scholar Isaacs’ research group synthesized and isolated a series of new types of melon rings with specific structures, such as the trans six-membered melon ring reported in 2005 ring (Q[6]*) and trans seven-membered melon ring (Q[7]*); in 2006, a dislocation-bridged ten-membered melon ring was synthesized; in 2007, a dislocation-bridged six-membered melon ring was synthesized ; the missing six-membered melon ring was reported in 2011. It makes people realize that the cucurbit ring is a macrocyclic cage compound with one or several hydrophobic cavities formed by n glycoside urea units and 2n methylene bridges, and the open ports are covered with polar carbonyl oxygen atoms. The melon ring cavity can not only contain non-polar organic molecules, but also use the terminal polar carbonyl oxygen to coordinate with cations such as metals, thus forming a unique melon ring chemistry, and because of its novelty and involvement The wide range of research fields (including host-guest chemistry, supramolecular chemistry, biochemistry, medicinal chemistry, polymers, materials, catalysis, etc.) has attracted the attention of scholars from all over the world.

Although there are many members of the common melon ring family, such as the five-, six-, seven-, eight-, and ten-membered melon rings, as well as the trans six- and seven-membered melon rings, dislocation bridging six, and ten-membered melon rings mentioned above. So far, there is no report on the isolation and characterization of melon rings with a polymerization degree greater than 10 by a research group at home and abroad. For the existing five-, six-, seven-, eight-, and ten-membered melon rings, those with an odd degree of polymerization generally have better water solubility, such as the five-membered melon ring (Q[5]: solubility ²⁰ is about 5.6g) , Seven-membered melon ring (Q[7]: the solubility ^{of 20} is about 1.7g); while the melon ring with an even degree of polymerization is extremely difficult to dissolve in water, such as Q[6], Q[8] and Q[10] , are often troubled by the solubility of the cucurbit ring when performing host-guest chemistry. In addition, the oil solubility of these melon rings is not good, and the research on host-guest chemistry of oil-soluble guests is limited, which affects the development of melon ring chemistry. At present, the host-guest chemistry, supramolecular chemistry, biochemistry, and medicinal chemistry in solution are mainly based on the seven-membered melon ring with good water solubility. Therefore, researchers from various countries have been working hard to find melon rings that are not only hydrophilic but also oil-soluble, so that the chemical content of the host and guest of the melon rings will be more colorful.

This patent application is the synthesis and separation of the spliced fourteen-membered melon ring (tQ[14]), and the most powerful means to characterize the new compound by using NMR (hydrogen spectrum, carbon spectrum), mass spectrometry, and single crystal structure analysis. The obtained nine-yuan melon ring was confirmed accurately. Utilize glycoside urea and paraformaldehyde under the condition of concentrated hydrochloric acid medium, reflux temperature for 5-8 hours, cool, add water step by step to dilute to separate eight-membered melon ring (Q[8]) and six-membered melon ring (Q[8]) with poor water solubility Q[6]) and a small amount of ten-membered melon rings (Q[5]Q[10]) including the non-membered melon rings. Concentrate the mother liquor containing five-membered cucurbit rings (Q[5]), seven-membered cucurbit rings (Q[7]), a small amount of spliced fourteen-membered cucurbit rings (tQ[14]) and a small amount of glycoside uridine polymers, and load To Dowex cationic exchange resin is the chromatographic column of stationary phase, with 1:(1～4):(0.01～1) water: acetic acid: concentrated hydrochloric acid is eluent, obtains five-membered melon ring (Q[5 ]), seven-membered melon ring (Q[7]), etc., and finally a pure spliced fourteen-membered melon ring (tQ[14]). The property research shows that the spliced fourteen-membered cucurbit ring (tQ[14]) has good water solubility and can be dissolved in polar organic solvents such as dimethyl sulfoxide and dimethyl formamide, showing its special hydrophilic and lipophilic properties.

Summary of the invention: The purpose of this invention is to synthesize, isolate and study new cucurbit ring compounds. The spliced fourteen-membered cucurbit ring (tQ[14]) reported in this invention is a new member of the cucurbit ring family that has been reported so far. member. The compound is composed of 14 glycoside uridine monomers (C ₄ H ₆ N ₄ O ₂ ) bridged by 28 methylene groups (-CH ₂ -) to form a folded "8"-shaped cage compound. Its chemical composition has the general formula It is: C ₈₄ H ₈₄ N ₅₆ O ₂₈ .

The structure is shown in Figure 1; the molecular weight is 2324; it is a white crystal, easily soluble in water and polar organic solvents, such as dimethyl sulfoxide.

The synthesis and isolation method of the new member of the cucurbit ring family of the present invention—twisting fourteen-membered cucurbit ring (tQ[14]), includes the synthesis method of the mixture of twisting fourteen-membered cucurbit ring and other cucurbit rings. The glycoside urea and paraformaldehyde are heated and refluxed at 100°C for 5~8 hours in concentrated hydrochloric acid medium, the weight ratio of glycoside urea and paraformaldehyde is 2~2.5:1, and cooled to obtain a mixed solution of various melon rings , and then follow these steps in order to separate:

(1) Under strong stirring, slowly pour the mixture into methanol, the volume ratio of the mixture to methanol is 1:8~12, to obtain a light yellow precipitate, filter to obtain a filter residue, which is a mixture of various melon rings ;

(2) Dry the filter residue at room temperature to obtain light yellow powder;

(3) Extract the yellow powder with 2~3 times the amount of neutral boiling water, oscillate ultrasonically for 3~5 minutes, and repeatedly extract 5~8 times;

(4) Concentrate the extract until the concentration of the concentrate is 1.0-1.1 grams of solids per milliliter.

(5) Load the concentrated solution onto a silica gel G or Dowex cation exchange resin column.

(6) Rinse with a volume ratio of 1:(1~4):(0.01~1) water:acetic acid:concentrated hydrochloric acid solution to separate Q[5], Q[7], and tQ[14] in sequence.

Separation step (4) During the process of concentrating the leach solution, if there are other white crystals of melon rings with less solubility, the white crystals should be filtered before proceeding to step (5).

Step (5) The column chromatography stationary phase is silica gel G or Dowex cationic exchange resin.

Step (6) is to gradually increase the polarity of the eluent according to the eluted substances, that is, to increase the ratio of acetic acid and hydrochloric acid. When leaching tQ[14], the ratio of acetic acid and hydrochloric acid reaches the maximum value.

The twisted fourteen-membered melon ring (tQ[14]) referred to in the patent of the present invention is the most powerful means to characterize the new compound through NMR (hydrogen spectrum, carbon spectrum), mass spectrum, single crystal structure analysis, etc. The fourteen-membered melon ring (tQ[14]) was followed for an unmistakable confirmation.

Description of drawings :

Fig. 1 Schematic diagram of the crystal structure of the twisted fourteen-membered melon ring (tQ[14]) (left panel): top view; (right panel): side view.

Fig. 2 The ¹ H NMR spectra of spliced fourteen-membered melon ring (tQ[14]) in deuterated water (top) and deuterated dimethyl sulfoxide (bottom), respectively.

Fig. 3 The ¹³ C NMR spectra of spliced fourteen-membered melon ring (tQ[14]) in deuterated water (upper picture) and deuterated dimethyl sulfoxide (lower picture), respectively.

Fig. 4 Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) of spliced fourteen-membered melon ring (tQ[14]).

Fig. 5 The infrared spectrum of the complex formed by spliced fourteen-membered cucurbit ring (tQ[14]) and rare earth metal ion Eu.

Figure 6. Differential thermal analysis spectrum (left figure) of the spliced fourteen-membered cucurbit ring (tQ[14]) and the complex formed by the spliced fourteen-membered cucurbit ring (tQ[14]) and the rare earth metal ion Eu; Reanalyzed spectrum (right panel).

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Specific implementation method:

Example 1: Synthetic implementation method of spliced fourteen-membered melon ring (tQ[14]):

Weigh 50 grams of glycoside urea, 20 grams of paraformaldehyde, 200 mL of concentrated hydrochloric acid, reflux for 6 hours, and cool. Under strong stirring, slowly pour the reaction solution into methanol, the volume ratio of the mixture to methanol is 1:8~12, and a light yellow precipitate is obtained, which is filtered to obtain a filter residue, which is a mixture of various melon rings. Use 2~3 times the amount of neutral boiling water to extract the yellow powder, oscillate ultrasonically for 3~5 minutes, and repeatedly extract 5~8 times. Concentrate the filtrate containing five-membered cucurbit rings (Q[5]), seven-membered cucurbit rings (Q[7]), a small amount of spliced fourteen-membered cucurbit rings (tQ[14]) and a small amount of glycoside urea polymers to a certain Volume (not too viscous, so as not to affect the sample on the column, take 15 mL of the concentrated solution (1.0-1.1 grams of solid per milliliter). Load the concentrated solution on a chromatographic column (40mm ?? 800mm) with silica gel G as the stationary phase, Take 1: (1 ~ 4): (0.01 ~ 1) water: acetic acid: concentrated hydrochloric acid as the eluent. Increase the polarity of the eluent according to the material gradient of the elution, that is, the amount of acetic acid and hydrochloric acid. Obtained accordingly The five-membered melon ring (Q[5]) and the seven-membered melon ring (Q[7]) were finally obtained by splicing the fourteen-membered melon ring (tQ[14]). The yield is about 1% of the theoretical yield.

Example 2: Synthetic implementation method of spliced fourteen-membered melon ring (tQ[14]):

Weigh 50 grams of glycoside urea, 20 grams of paraformaldehyde, 200 mL of concentrated hydrochloric acid, reflux for 6 hours, and cool. Under strong stirring, slowly pour the reaction solution into methanol, the volume ratio of the mixture to methanol is 1:8~12, and a light yellow precipitate is obtained, which is filtered to obtain a filter residue, which is a mixture of various melon rings. Use 2~3 times the amount of neutral boiling water to extract the yellow powder, oscillate ultrasonically for 3~5 minutes, and repeatedly extract 5~8 times. Concentrate the filtrate containing five-membered cucurbit rings (Q[5]), seven-membered cucurbit rings (Q[7]), a small amount of spliced fourteen-membered cucurbit rings (tQ[14]) and a small amount of glycoside urea polymers to a certain Volume (not too viscous, so as not to affect the sample on the column, take 15 mL of the concentrated solution (1.0-1.1 grams of solids per mL). Load the concentrated solution on a chromatographic column (40mm?? 800mm), using 1:(1~4):(0.01~1) water: acetic acid: concentrated hydrochloric acid as the eluent. Increase the polarity of the eluent according to the material gradient of the elution, that is, the amount of acetic acid and hydrochloric acid. According to this, the five-membered melon ring (Q[5]) and the seven-membered melon ring (Q[7]) are obtained, and finally the pure product is spliced with the fourteen-membered melon ring (tQ[14]). The yield accounts for about the theoretical yield 1%.

Claims (5)

1. newcomer in the melon ring family-hinge joint ten quaternary melon rings (tQ[14]), this compound is by 14 glycosides urea monomer (C ₄H ₆N ₄O ₂) by 28 methylene radical (CH ₂-) bridging forms the cage compound of the folding figure of eight, its chemical constitution general formula is: C ₈₄H ₈₄N ₅₆O ₂₈, structure is referring to accompanying drawing 1; Molecular weight is 2324; Be white crystal, soluble in water and polar organic solvent is such as methyl-sulphoxide.

2. according to the synthetic separation method of newcomer-hinge joint ten quaternary melon rings in the melon ring claimed in claim 1 family (tQ[14]), the synthetic method that comprises the mixture of hinge joint ten quaternary melon rings and other melon ring, be with glycosides urea and Paraformaldehyde 96 in the concentrated hydrochloric acid medium, 100 ℃ of reflux 5 ~ 8 hours, the weight proportion of glycosides urea and Paraformaldehyde 96 is 2 ~ 2.5:1, cool off, get the mixed solution of multiple melon ring, it is characterized in that following these steps to successively separate:

(1) under violent stirring, mixed solution slowly to be poured in the methyl alcohol, the volume ratio of mixed solution and methyl alcohol is 1:8 ~ 12, gets faint yellow precipitation, filters, and gets filter residue, filter residue is the mixture of multiple melon ring;

(2) with the filter residue Air drying, get pale yellow powder;

(3) the neutral boiling water with 2 ~ 3 times of amounts leaches yellow powder, ultrasonic oscillation 3 ~ 5 minutes, and lixiviate is 5 ~ 8 times repeatedly;

(4) vat liquor is concentrated, until being every milliliter, concentrated solution concentration contains solid 1.0-1.1 gram;

(5) with the upper silica gel G of concentrated solution filling or the cationic exchange resin column of Dowex;

(6) with volume ratio 1:(1 ~ 4): (0.01 ~ 1) water: acetic acid: concentrated hydrochloric acid solution drip washing, isolate successively Q[5], Q[7], and tQ[14].

3. the synthetic separation method of newcomer-hinge joint ten quaternary melon rings in the melon ring according to claim 2 family (tQ[14]), it is characterized in that separating step (4) is in the leaching liquid concentration process, when occurring if any the white crystals thing of the less melon ring of other solvability, carry out again step (5) after should be first will the white crystals thing filtering.

4. the synthetic separation method of newcomer-hinge joint ten quaternary melon rings in the melon ring according to claim 2 family (tQ[14]) is characterized in that the column chromatography stationary phase is silica gel G or the cationic exchange resin of Dowex.

5. the synthetic separation method of newcomer-hinge joint ten quaternary melon rings in the melon ring according to claim 2 family (tQ[14]), it is characterized in that the material that goes out according to drip washing, the polarity of step increase leacheate, namely increase acetic acid and hydrochloric acid proportioning, as drip washing tQ[14] time, acetic acid and hydrochloric acid proportioning reach maximum value.

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