CN108329225B - P-dibenzoyl dimer derivative and synthetic method and application thereof - Google Patents
P-dibenzoyl dimer derivative and synthetic method and application thereof Download PDFInfo
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- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
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- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
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Abstract
The invention discloses a p-dibenzoyl dimer derivative and a synthetic method and application thereof. The p-dibenzoyl dimer derivative has a structure shown in a general formula (I), wherein n is 1,2,3, R is C5‑C13Alkyl chains, phenyl or substituted phenyl, biphenyl or substituted biphenyl. The invention takes amino acid with side chain as aminoalkyl, p-dibenzoyl chloride and alkylamine as starting materials, and synthesizes the dimer derivative of p-dibenzoyl amide of amino acid alkyl amide through four-step reaction. The synthesized derivative has the potential of treating infection caused by gram-positive bacteria and gram-negative bacteria with drug resistance, is suitable for antibacterial surface treatment, particularly is used as an antibacterial active additive component for resisting pollution of the positive bacteria and the negative bacteria, and has high application value.
Description
Technical Field
The invention relates to a p-dibenzoyl dimer derivative, a preparation method and application thereof, in particular to a p-dibenzoyl dimer derivative of amino acid alkylamide, a preparation method thereof and application of the compound in the aspect of antibiosis. The invention belongs to the technical field of medicines.
Background
The problem of antibiotic resistance has become one of the most important public health issues in the 21 st century. The emergence of drug-resistant strains such as MRSE, MRSA, VRE and the like, and multi-drug-resistant bacteria negative bacteria such as pseudomonas aeruginosa, klebsiella pneumoniae, acinetobacter baumannii and the like becomes a significant threat to the health and survival of human beings at present and in the future. On the other hand, the development speed of conventional antibiotics cannot keep up with the drug resistance development speed of bacteria, so that the number of new antibiotics approved for clinical use is steadily decreasing, and therefore, the development of antibacterial drugs with new structures and new action modes to overcome the problem of drug resistance of bacteria is urgently needed.
The natural antibacterial peptide is the first defense line of immune system against the invasion of microorganisms, and has antibacterial and antifungal activities. Antimicrobial peptides are amphiphilic molecules with a net positive charge, having a topological conformation in which lipophilic residues and hydrophilic positive charges are distributed in different regions of the polypeptide. Unlike conventional antibiotics acting on specific targets in bacterial metabolic process, the antibacterial peptide acts on bacterial cell membranes by using the conformational characteristics of the antibacterial peptide, namely, the positive charge of the antibacterial peptide and the negative charge on the bacterial cell membranes are subjected to electrostatic attraction, and the hydrophobic residues of the antibacterial peptide are inserted into the bacterial cell membranes to destroy the integrity and increase the permeability of the bacterial cell membranes, thereby finally leading to irreversible bacterial death. The new action mechanism of the antibacterial peptide determines that the bacteria are not easy to induce drug resistance. However, the existing antibacterial peptide generally has the problems of weak antibacterial activity, poor stability, high production cost and the like, so an antibacterial peptide mimetic with a brand-new structure, strong antibacterial activity and good stability is urgently needed to be provided to solve the technical problems existing at present.
Disclosure of Invention
One of the purposes of the invention is to provide an antibacterial peptide mimic with a brand-new structure, and the antibacterial peptide mimic has the advantages of strong antibacterial activity, good stability and the like.
The second object of the present invention is to provide a method for preparing the above-mentioned antibacterial peptide mimetic.
A further object of the invention is the use of the above-mentioned antibacterial peptidomimetics for antibacterials.
In order to achieve the purpose, the invention adopts the following technical means:
according to the integral topological conformation and the antibacterial function of the antibacterial peptide, the p-dibenzoyl dimer derivative of the cationic amino acid alkylamide with a brand new structure is synthesized, and researches show that the synthesized derivative has the potential of treating infection caused by gram-positive bacteria and gram-negative bacteria including drug resistance, is suitable for antibacterial surface treatment, is particularly used as an antibacterial active additive component for resisting pollution of the positive bacteria and the negative bacteria, and has high application value.
The invention relates to a p-dibenzoyl dimer derivative, which has a structure shown in a general formula (I):
in the formula:
n is selected from any integer of 1,2 and 3;
r is selected from C5-C13Alkyl chains, phenyl or substituted phenyl, biphenyl or substituted biphenyl.
Among them, preferably, in the formula, n is 3.
Wherein, preferably, said C5-C13The alkyl chain comprising n-C5H11、n-C6H13、n-C7H14、n-C8H17、n-C9H19、n-C10H21、n-C11H23、n-C12H25、n-C13H27Phenyl or substituted phenyl, biphenylmethyl and substituted biphenylmethyl.
Furthermore, the invention also discloses a method for synthesizing the p-dibenzoyl dimer derivative, which comprises the following steps:
(2) the amino acid methyl ester 2-1 protected by the side chain Cbz and p-dibenzoyl chloride are reacted in CH2Cl2In a solvent, at NEt3Compound 2-2 is synthesized in the presence of a catalyst;
(2) hydrolyzing the dimethyl ester of the compound 2-2 to obtain a compound 2-3;
(3) carrying out condensation reaction on the compound 2-3 and amine, and then removing a benzyloxycarbonyl protecting group to obtain a compound of a general formula (I);
the synthetic scheme of the compounds of the invention is shown in figure 1.
Among them, it is preferable that the amine in the step (3) is selected from n-hexylamine, n-heptylamine, n-octylamine, n-nonylamine, n-decylamine, n-dodecylamine, n-tridecylamine, n-tetradecylamine, or 4-phenylbenzylamine.
Among them, preferably, the condensing agent in step (3) is EDC, HATU, HBTU, TBTU or BOP, more preferably EDC.
Furthermore, the invention also provides the application of the dibenzoyl dimer derivative in preparing antibacterial drugs. And as an antimicrobial component in the preparation of cosmetics, household products, textiles and plastics products.
Among them, the bacteria are preferably drug-resistant gram-positive bacteria or drug-resistant gram-negative bacteria. More preferably, the bacteria are methicillin-resistant staphylococcus epidermidis, methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus faecalis, escherichia coli and multidrug-resistant pseudomonas aeruginosa.
The p-dibenzoyl dimer derivative is an antibacterial peptide mimic, and is expected to be developed into a supplementary medicament or an antibiotic substitute for treating infectious diseases; in addition, the invention can also be used in the quality guarantee and quality guarantee of cosmetics, household products, textiles and plastic products, including surface antibacterial treatment, as an antibacterial active ingredient against gram-positive bacteria, gram-negative bacteria and the like.
Drawings
FIG. 1 is a scheme for the synthesis of compounds of the present invention.
1) Terephthaloyl dichloride, Et3N,CH2Cl2；2)LiOH,MeOH/H2O；3)i)RCH2NH2,EDC,HOBt,DIPEA,DMF；ii)TFA/CH2Cl2Or Pd/C, H2,HCl(aq),MeOH.
Abbreviation list
The invention disclosed herein uses the following chemical nomenclature:
DMF N, N-dimethylformamide
DIPEA N, N-diisopropylethylamine
EDC 1-ethyl- (dimethylaminopropyl) carbodiimide hydrochloride
HOBt 1-hydroxybenzotriazole
THF tetrahydrofuran
MeOH methanol
TFA trifluoroacetic acid
CH2Cl2Methylene dichloride
NEt3Triethylamine
TFA trifluoroacetic acid
Cbz carbobenzoxy acyl
MRSA methicillin-resistant Staphylococcus aureus
Detailed Description
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. The examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
EXAMPLE 1 Synthesis of Compound 2-2
Will N6- ((benzyloxycarbonyl)) -L-lysine methyl ester hydrochloride (10g,30.2mmol) was dissolved in anhydrous bisIn methyl chloride, the solution was cooled to-20 ℃. DIPEA (6.3mL,36.2mmol) was then added and p-dibenzoyl chloride (2.9g,13.7mmol) was added in portions. The reaction was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was neutralized with hydrochloric acid (0.1M) and diluted with 200ml of distilled water. After separation of the two phases, the aqueous phase was extracted three times with dichloromethane (3 × 100 mL). The combined organic phases were washed with purified water, saturated brine and dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was separated by silica gel column chromatography to give 2-2(9.76g, 95.1%) as a white solid.1H NMR(400MHz,CDCl3)δ7.85(s,2H),7.34-7.31(m,5H),6.85(d,J＝6.5Hz,1H),5.06(d,J＝12.7Hz,1H),5.01(d,J＝12.7Hz,1H),4.86(br.s 1H),4.82-4.75(dd,J＝6.0,11.0Hz,1H),3.78(s,3H),3.21-3.19(m,2H),2.04-1.97(m,1H),1.85-1.83(m,1H),1.56-1.40(m,4H).13C NMR(101MHz,CDCl3)δ172.93,166.32,156.61,136.57,136.48,128.49,128.06,127.98,127.40,66.58,52.55,52.51,40.34,31.83,29.37,22.37.HRMS(ESI-TOF)m/z Calcd for C38H50N5O10[M+NH4]+:736.3558,found:736.3556.
EXAMPLE 2 Synthesis of Compounds 2-3
Compound 2-2 was suspended in methanol (100mL) and cooled to 0 ℃. Lithium hydroxide (13.5mL,27mmol,2M aqueous solution) was added dropwise to the suspension, and the reaction mixture was allowed to react overnight at room temperature. Upon completion of the reaction, the pH of the solution was adjusted to 7 with citric acid in an ice water bath. The white filter cake obtained by filtration was washed with water and a small amount of methanol and dried under vacuum to give 2-3(7.04g, 84.3%) as a white solid.1H NMR(400MHz,CD3OD)δ7.94(s,2H),7.32-7.27(m,5H),5.09-5.03(m,2H),4.59(dd,J＝4.5,9.2Hz,1H),3.15-3.12(m,2H),2.01-1.99(m,1H),1.92-1.86(m,1H),1.61-1.49(m,4H).13C NMR(101MHz,CD3OD)δ174.95,167.17,157.37,138.55,137.60,129.60,128.98,128.95,128.69,66.35,54.09,31.52,30.30,24.49.HRMS(ESI-TOF)m/z Calcd for C36H42N4NaO10[M+Na]+:713.2799,found:713.2800.
EXAMPLE 3 Synthesis of end products 2-4(a-i)
General procedure for the Synthesis of the final products 2-4 (a-i):
compound 2-3(1 eq) was dissolved in anhydrous DMF (5 mL). EDC (2.4 equiv.), HOBt (3.6 equiv.) and DIPEA (2.88 equiv.) were added sequentially at 0 ℃. The reaction mixture was stirred at this temperature for 0.5-1 h, then different amines (2.4 eq) and DIPEA (2.4 eq) were added and the reaction was stirred at 30 ℃ for 1 day. After completion of the reaction, DMF was removed under reduced pressure, and the residue was separated by silica gel column chromatography to obtain a crude product. The crude product was dissolved in a mixed solvent of DCM (4mL) and TFA (8mL), and the reaction was refluxed for 4 to 6 hours. The solvent is removed under reduced pressure and the residue is chromatographed on C-18 reverse phase silica gel (H)2MeOH 1:1 to 1:10), solvent was removed and lyophilized to give white powder as the final product.
Example 3-1: n is a radical of1,N4-bis ((S) -6-amino-1- (hexylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4a)
This compound was synthesized from compound 2-3(100mg,0.14mmol) and n-hexylamine (34.4mg,0.34mmol) according to the general procedure to give (45.5mg, 55.2%) as a white powder.1H NMR(400MHz,CD3OD)δ8.00(s,2H),4.54(dd.J＝6.4,11Hz,1H),3.21(t,J＝7.09Hz,2H),2.96-2.91(m,2H),1.98-1.80(m,2H),1.77-1.68(m,2H),1.57-1.45(m,4H),1.37-1.29(m,6H),0.90(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.99,169.25,138.07,128.77,55.39,40.53,40.51,32.61,32.58,30.30,28.13,27.61,23.60,14.33.HRMS(ESI-TOF)m/z Calcd for C32H57N6O4[M+H]+:589.4441,found:589.4442.
Example 3-2: n is a radical of1,N4-bis ((S) -6-amino-1- (heptylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4b)
The compound was prepared by reacting compound 2-3(100mg,0.14mmol) with n-heptyleneAmine (39.1mg,0.34mmol) was synthesized according to the general procedure to give (34mg, 39.3%) as a white powder 1H NMR (400MHz, CD)3OD)δ7.98(s,2H),4.55(dd,J＝5.8,8.7Hz,1H),3.31(t,J＝7.1Hz,2H),3.06-2.92(m,2H),1.99-1.80(m,2H),1.77-1.68(m,2H),1.61-1.45(m,4H),1.34-1.31(m,8H),0.90(t,J＝7.1Hz,3H).13C NMR(101MHz,CD3OD)δ174.09,169.26,138.04,128.84,55.52,40.53,32.96,32.59,30.39,30.10,28.16,27.94,24.20,23.67,14.47.HRMS(ESI-TOF)m/z Calcd for C34H61N6O4[M+H]+:617.4754,found:617.4744.
Examples 3 to 3: n is a radical of1,N4-bis ((S) -6-amino-1- (octylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4c)
This compound was synthesized from compound 2-3(100mg,0.14mmol) and n-octylamine (44mg,0.34mmol) according to the general procedure to give (41.3mg, 45.6%) as a white powder.1H NMR(400MHz,CD3OD)δ8.00(s,2H),4.56(dd.J＝6.0,11.0Hz,1H),3.22(t,J＝7.2H,2H),2.96-2.91(m,2H),1.99-1.80(m,2H),1.77-1.69(m,2H),1.60-1.47(m,4H),1.31-1.28(m,10H),0.89(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.99,169.25,138.08,128.79,55.35,40.51,32.96,32.57,30.37,28.16,27.96,24.12,23.70,14.43.HRMS(ESI-TOF)m/z Calcd for C36H65N6O4[M+H]+:645.5067,found:645.5052.
Examples 3 to 4: n is a radical of1,N4-bis ((S) -6-amino-1- (nonanamido) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4d)
This compound was synthesized from compound 2-3(100mg,0.14mmol) and n-nonanamine (49mg,0.34mmol) according to the general procedure to give (41mg, 43.5%) as a white powder.1H NMR(400MHz,CD3OD)δ7.96(s,2H),4.52(dd.J＝6.0,11.0Hz,1H),3.18(t,J＝7.2H,2H),2.94-2.90(m,2H),1.97-1.80(m,2H),1.77-1.68(m,2H),1.60-1.45(m,4H),1.35-1.28(m,12H),0.89(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.96,169.22,138.09,128.78,55.35,40.54,40.52,33.00,32.59,30.62,30.39,30.34,28.15,27.94,24.10,23.67,14.40.HRMS(ESI-TOF)m/z Calcd for C38H69N6O4[M+H]+:673.5380,found:673.5377.
Examples 3 to 5: n is a radical of1,N4-bis ((S) -6-amino-1- (decylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4e)
This compound was synthesized from compound 2-3(100mg,0.14mmol) and n-decylamine (49mg,0.34mmol) according to the general procedure to give (38mg, 38.6%) as a white powder.1H NMR(400MHz,CD3OD)δ7.98(s,2H),4.54(dd.J＝6.4,11Hz,1H),3.21(t,J＝7.2Hz,2H),2.96-2.91(m,2H),1.99-1.68(m,2H),1.77-1.69(m,2H),1.58-1.45(m,4H),1.37-1.27(m,14H),0.89(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.99,169.25,138.08,128.80,55.34,40.52,33.05,32.58,30.71,30.69,30.45,30.42,30.37,28.16,27.96,24.13,23.73,14.44.HRMS(ESI-TOF)m/z Calcd for C40H73N6O4[M+H]+:701.5693,found:701.5700.
Examples 3 to 6: n is a radical of1,N4-bis ((S) -6-amino-1- (dodecaamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4f)
This compound was synthesized from compound 2-3(200mg,0.28mmol) and n-dodecylamine (126mg,0.68mmol) according to the general procedure to give (54.8mg, 25.8%), a white powder, 1H NMR (400MHz, CD3OD) δ 7.97(s,2H),4.54(t.J ═ 6.75Hz,1H),3.21(m,2H),2.94(t, J ═ 7.2Hz,2H),1.97-1.81(m,2H),1.74-1.69(m,2H),1.61-1.45(m,4H),1.32-1.28(m,18H),0.89(t, J ═ 7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.98,169.23,138.07,128.75,55.34,40.49,33.05,32.58,30.76,30.72,30.70,30.68,30.45,30.40,30.35,28.14,27.95,24.10,23.71,14.43.HRMS(ESI-TOF)m/z Calcd for C44H81N6O4[M+H]+:757.6319,found:757.6306.
Examples 3 to 7: n is a radical of1,N4-bis ((S) -6-amino-1- (tridecylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4g)
This compound was synthesized from compound 2-3(200mg,0.28mmol) and n-tridecylamine (136mg,0.68mmol) according to the general procedure to give (42.5mg, 19.3%) as a white powder.1H NMR(400MHz,CD3OD)δ8.01(s,2H),4.59(t.J＝6.75Hz,1H),3.26(m,2H),2.99(t,J＝7.2Hz,2H),2.03-1.84(m,2H),1.79-1.73(m,2H),1.57-1.52(m,4H),1.32-1.29(m,20H),0.91(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.93,169.24,138.13,128.76,55.27,40.43,33.06,32.62,30.76,30.75,30.70,30.68,30.45,30.40,30.36,28.18,27.96,24.08,23.72,14.42.HRMS(ESI-TOF)m/z Calcd for C46H85N6O4[M+H]+:785.6632,found:785.6613.
Examples 3 to 8: n is a radical of1,N4-bis ((S) -6-amino-1- (tetradecylamino) -1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4h)
This compound was synthesized from compounds 2-3(200mg,0.28mmol) and n-tetradecylamine (145mg,0.68mmol) according to the general procedure to give (36mg, 15.8%) as a white powder.1H NMR(400MHz,CD3OD)δ7.97(s,2H),4.54(t.J＝6.9Hz,1H),3.21(t,J＝6.3Hz,2H),2.93(t,J＝7.5Hz,2H),1.94-1.82(m,2H),1.72-1.70(m,2H),1.52-1.50(m,4H),1.31-1.27(m,22H),0.90(t,J＝7.2Hz,3H).13C NMR(101MHz,CD3OD)δ173.94,169.24,138.11,128.76,55.27,40.51,33.07,32.60,30.79,30.77,30.76,30.72,30.70,30.48,30.42,30.36,27.18,27.96,24.09,23.73,14.44.HRMS(ESI-TOF)m/z Calcd for C48H89N6O4[M+H]+:813.6945,found:813.6913.
Examples 3 to 9: n is a radical of1,N4-bis ((S) -6-amino-1- (([1, 1' -bisbenzene)]-4-ylmethyl) amino-1-carbonylhex-2-yl) -1, 4-benzenedicarboxamide (2-4i)
This compound was synthesized from compound 2-3(200mg,0.28mmol) and 4-phenylbenzylamine (124mg,0.68mmol) according to the general procedure to give (16mg, 7.5%) as a white powder.1H NMR(400MHz,CD3OD)δ7.99(s,2H),7.59-7.56(m,4H),7.44-7.37(m,4H),7.34-7.30(m,1H),4.62(dd.J＝7.0,11.0Hz,1H),4.46(s,2H),2.95-2.90(m,2H),2.02-1.86(m,2H),1.76-1.68(m,2H),1.62-1.45(m,2H).13C NMR(101MHz,CD3OD)δ174.14,139.47,142.04,141.48,138.96,138.12,129.87,129.06,128.82,128.36,128.10,127.87,55.43,43.83,40.52,32.48,28.15,24.13.HRMS(ESI-TOF)m/z Calcd for C46H53N6O4[M+H]+:753.4128,found:753.4111.
Test examples in vitro antibacterial Activity test of the Compound of the present invention
Test materials and sources
1. Test compounds: the p-dibenzoyl dimer derivatives prepared in examples 3-1 to 3-9 of the present invention.
2. Bacteria for experiments: methicillin-resistant staphylococcus epidermidis (MRSE, RP62A), methicillin-resistant staphylococcus aureus (MRSA, ATCC 33591), vancomycin-resistant enterococcus faecalis (VRE, ATCC 25922), escherichia coli (e.coli, ATCC 25922), multidrug-resistant pseudomonas aeruginosa (p.aeruginosa, ATCC 27853).
Second, test method
1. And (3) detecting a culture medium:
the liquid culture medium formula is as follows (g/L): peptone: 20.0 g; beef extract: 5.0 g; sodium chloride: 5.0 g. The pH value is 7.5 +/-0.1. The formula usage is as follows: weighing the raw materials, heating and dissolving in 1000ml of distilled water, stirring continuously, boiling for 1 minute, subpackaging in a Erlenmeyer flask, and autoclaving at 121 ℃ for 20 minutes for later use.
2. Grouping tests:
sample group: respectively adding 2 mul/hole test compound into a 96-hole plate, and respectively adding suspensions of methicillin-resistant staphylococcus epidermidis, methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus faecalis, escherichia coli and multidrug-resistant pseudomonas aeruginosa into corresponding holes, wherein the total volume is 150 mul/hole.
Detection of bacteria control group: DMSO with the same volume as the test compound of the sample group is respectively added into a 96-well plate, and suspension of methicillin-resistant staphylococcus epidermidis, methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus faecalis, escherichia coli and multidrug-resistant pseudomonas aeruginosa is respectively added into corresponding holes, wherein the total volume is 150 mu l/hole.
Medium blank control group: 150 μ l/well assay medium.
3. And (3) testing a sample:
the solutions were prepared for assay by dilution in duplicate gradients after 9 samples were dissolved in DMSO to a final concentration of between 0.5-100. mu.g/mL.
Third, test results
The results of the three measurements are shown in Table 1 below:
TABLE 1
Experimental results show that the compounds 2-4d have strong capacity of resisting gram-positive bacteria and gram-negative bacteria and have various application prospects.
Claims (12)
1. A p-dibenzoyl dimer derivative having the structure of formula (I):
in the formula:
n is selected from any integer of 1,2 and 3;
r is selected from C5-C13Alkyl chains, phenyl or biphenyl.
2. The p-dibenzoyl dimer derivative of claim 1, wherein n is 3.
3. The p-dibenzoyl dimer derivative of claim 1, wherein C is5-C13Alkyl chain being n-C5H11、n-C6H13、n-C7H14、n-C8H17、n-C9H19、n-C10H21、n-C11H23、n-C12H25Or n-C13H27。
4. A method for synthesizing the p-dibenzoyl dimer derivative of claim 1, comprising the steps of:
(1) the amino acid methyl ester 2-1 protected by the side chain Cbz and p-dibenzoyl chloride are reacted in CH2Cl2In a solvent, at NEt3Compound 2-2 is synthesized in the presence of a catalyst;
(2) hydrolyzing the dimethyl ester of the compound 2-2 to obtain a compound 2-3;
(3) carrying out condensation reaction on the compound 2-3 and amine, and then removing a benzyloxycarbonyl protecting group to obtain a compound of a general formula (I);
wherein n is selected from any integer of 1,2 and 3, and R is selected from C5-C13Alkyl chains, phenyl or biphenyl.
5. The method of claim 4, wherein C is5-C13Alkyl chain being n-C5H11、n-C6H13、n-C7H14、n-C8H17、n-C9H19、n-C10H21、n-C11H23、n-C12H25Or n-C13H27。
6. The process of claim 4, wherein the amine of step (3) is selected from n-hexylamine, n-heptylamine, n-octylamine, n-nonylamine, n-decylamine, n-dodecylamine, n-tridecylamine, n-tetradecylamine, and 4-phenylbenzylamine.
7. The method of claim 4, wherein the condensing agent of step (3) is EDC, HATU, HBTU, TBTU or BOP.
8. The method of claim 7 wherein the condensing agent of step (3) is EDC.
9. Use of a dibenzoyl dimer derivative according to any one of claims 1-3 for the preparation of an antibacterial agent.
10. Use of the p-dibenzoyl dimer derivative according to any one of claims 1 to 3 as an antibacterial ingredient in the preparation of cosmetics, household products, textiles and plastics products.
11. The use of claim 9 or 10, wherein the bacteria are resistant gram positive or negative bacteria.
12. The use of claim 11, wherein the bacteria are methicillin-resistant staphylococcus epidermidis, methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus faecalis, escherichia coli, multidrug-resistant pseudomonas aeruginosa.
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