CN113999163A - Synthetic cannabinoid hapten compounds, methods of making and uses thereof - Google Patents
Synthetic cannabinoid hapten compounds, methods of making and uses thereof Download PDFInfo
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- CN113999163A CN113999163A CN202111294303.5A CN202111294303A CN113999163A CN 113999163 A CN113999163 A CN 113999163A CN 202111294303 A CN202111294303 A CN 202111294303A CN 113999163 A CN113999163 A CN 113999163A
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- synthetic cannabinoid
- hapten
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
Abstract
The invention relates to a synthetic cannabinoid hapten compound, a preparation method and application thereof.
Description
Technical Field
The invention relates to a synthetic cannabinoid hapten compound and a preparation method and application thereof.
Background
Aiming at the detection of trace and trace substances in a test material, an immunoassay based on antibody-antigen reaction is the most common and efficient detection means in field detection. One of the key steps in immunoassay is the synthesis of hapten, which requires modification of the antigen molecule to introduce a group that can attach to the arm.
The introduction of the arm should keep the chemical property and structural information of the antigen molecule as much as possible, and the introduction steps should be simple and efficient, and the antigen molecule with a special group is the hapten molecule.
The synthetic cannabinoids are drugs with strong addiction, and the whole class of tubulose compounds is announced in China at present. The synthetic cannabinoid molecule has a simple structure, and therefore, the place to introduce the synthetic cannabinoid hapten needs to be carefully selected.
Accordingly, the present invention provides a synthetic cannabinoid hapten compound for use in detecting the content of synthetic cannabinoids.
Disclosure of Invention
The main object of the present invention is to overcome the above mentioned disadvantages of the existing products and to provide a synthetic cannabinoid hapten compound, its preparation method and use.
In order to achieve the above objects, the present invention employs the following technical scheme for synthesizing cannabinoid hapten compounds:
the structural formula of the compound is as follows:
wherein Linker is a single bond, a double bond, a triple bond, C1-8A hydrocarbon group of (a), p-phenyl group, m-phenyl group, o-phenyl group, 1, 4-divinylphenyl group, vinylphenyl group, ethynylphenyl group, 1, 4-diacetylynylphenyl group, biphenyl group, 1, 4-methylenephenyl group, or 9, 10-anthracenyl group;
x, Y each independently is O, NH or no atom;
R1、R2each independently is substituted or unsubstituted C6-C10Aryl of (2), substituted or unsubstituted C3-C10Substituted or unsubstituted heterocyclyl containing 1 to 3 heteroatoms; substituted or unsubstituted heterocyclyl-substituted methyl or ethyl containing 1 to 3 heteroatoms.
Preferably, the compound has the following structural formula:
the invention also provides a preparation method of the synthetic cannabinoid hapten compound, wherein tertiary leucine methyl ester and N-5 benzyl valerate-carbazole 3-formic acid are subjected to condensation reaction to generate a benzyl protected intermediate; deprotection of the intermediate under reducing conditions produces the synthetic cannabinoid hapten compound.
Preferably, the preparation method comprises the following steps:
(1) carrying out condensation reaction on tert-leucine methyl ester and N-5 benzyl valerate-carbazole 3-formic acid under the catalysis of DMAP to generate a benzyl protected intermediate;
(2) deprotecting said benzyl-protected intermediate under reductive conditions to produce said synthetic cannabinoid hapten compound;
the invention also provides application of the synthetic cannabinoid hapten compound in detecting the content of the synthetic cannabinoid.
The synthetic cannabinoid hapten compound containing terminal carboxyl and the preparation method thereof can conveniently prepare antigen by connecting protein through subsequent amidation, esterification and other reactions, and is one of necessary technologies in the rapid detection of synthetic cannabinoids.
Drawings
FIG. 1 is a high resolution mass spectrum of the synthetic cannabinoid hapten compound of example 1.
FIG. 2 is a scheme showing the synthesis of cannabinoid hapten compounds in example 11H-NMR spectrum.
FIG. 3 is a synthesis of cannabinoid hapten compound from example 113C-NMR spectrum.
Figure 4 is an HPLC profile of the synthetic cannabinoid hapten compound of example 1.
Detailed Description
In order to clearly understand the technical contents of the present invention, the following examples are given in detail.
Example 1
The preparation method of the synthetic cannabinoid hapten compound provided by the invention specifically comprises the following steps:
dissolving tert-leucine methyl ester (159mg,1.1mmol) in 15mL of anhydrous carbon tetrachloride at-20 ℃, adding 4-Dimethylaminopyridine (DMAP) (5.6mg,0.05mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI) (382mg,2mmol), then adding dropwise anhydrous oxygen-free carbon tetrachloride solution (15mL) of 5-carbazolylpentanoate (405mg,1mmol), stirring and slowly raising the temperature to room temperature, keeping the room temperature for 12 hours, then heating to 40 ℃ and heating for 2 hours; after cooling, ammonium chloride solution was added, the solvent was removed by rotary evaporation, 150mL of ethyl acetate was added and dissolved, and the insoluble material was removed by filtration through celite, using 30mL of diethyl ether-ethyl acetate 1:1, washing diatomite by the solution, separating liquid, extracting for 3 times by using dichloromethane, combining organic phases, and drying by using anhydrous magnesium sulfate; filtering to remove the drying agent, and performing rotary evaporation to remove the solvent; purifying by silica gel column chromatography (petroleum ether: ethyl acetate 4:1) to obtain methyl protected intermediate;
the intermediate was dissolved in 25mL of dichloromethane without further purification, 10% Pd/C was added, heated to 60 ℃ and stirred overnight; the reaction solution was washed with ether, the insoluble matter was removed by filtration with celite, the celite was washed with 30mL of a solution of ethyl acetate-methanol 1:1, the pH was adjusted to 2 with 30% hydrochloric acid, a large amount of solid was precipitated, and the solid was filtered, air-dried, and recrystallized with acetone-petroleum ether to give a synthetic cannabinoid hapten compound as a white solid (289mg, 66%).
The corresponding high resolution mass spectrum, hydrogen spectrum, carbon spectrum and HPLC spectrum are shown in FIGS. 1, 2, 3 and 4, respectively.
1H NMR(600MHz,Methanol-d4)δ8.66–8.63(m,1H),8.15(d,J＝7.7Hz,1H),7.95(dd,J＝8.6,1.6Hz,1H),7.56–7.44(m,3H),7.24(t,J＝7.4Hz,1H),4.67(s,1H),4.38(t,J＝7.2Hz,2H),3.76(s,3H),2.29(t,J＝7.3Hz,2H),1.88(p,J＝7.4Hz,2H),1.64(p,J＝7.4Hz,2H),1.30–1.19(m,1H),1.12(s,9H).
13C NMR(151MHz,Methanol-d4)δ177.14,173.49,171.20,143.82,142.48,127.57,126.47,125.63,124.17,123.85,121.55,121.30,120.85,110.46,109.75,62.79,62.70,52.35,43.65,35.67,34.51,30.82,29.45,27.35,23.64.(ESI/TOF)m/z:Calcd.for C25H31N2O5[M+H]+439.2233；Found:439.2227.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (5)
1. A synthetic cannabinoid hapten compound having the structural formula:
wherein Linker is a single bond, a double bond, a triple bond, C1-8A hydrocarbon group of (a), p-phenyl group, m-phenyl group, o-phenyl group, 1, 4-divinylphenyl group, vinylphenyl group, ethynylphenyl group, 1, 4-diacetylynylphenyl group, biphenyl group, 1, 4-methylenephenyl group, or 9, 10-anthracenyl group;
x, Y each independently is O, NH or no atom;
R1、R2each independently is substituted or unsubstituted C6-C10Aryl of (2), substituted or unsubstituted C3-C10Substituted or unsubstituted heterocyclyl containing 1 to 3 heteroatoms; substituted or unsubstituted heterocyclyl-substituted methyl or ethyl containing 1 to 3 heteroatoms.
2. The synthetic cannabinoid hapten compound according to claim 1, wherein said compound has the following structural formula:
3. a process for the synthesis of cannabinoid hapten compounds as claimed in claim 1 or 2, characterized in that tertiary leucine methyl ester is subjected to condensation reaction with N-5 benzyl valerate-carbazole 3-carboxylic acid to yield benzyl protected intermediates; deprotection of the intermediate under reducing conditions produces the synthetic cannabinoid hapten compound.
4. The method of claim 3, comprising the steps of:
(1) carrying out condensation reaction on tert-leucine methyl ester and N-5 benzyl valerate-carbazole 3-formic acid under the catalysis of DMAP to generate a benzyl protected intermediate;
(2) deprotecting said benzyl-protected intermediate under reductive conditions to produce said synthetic cannabinoid hapten compound;
5. use of the synthetic cannabinoid hapten compound of claim 1 or 2 for detecting the content of synthetic cannabinoid.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1814301A (en) * | 1996-09-30 | 2006-08-09 | 茨诺瓦研究有限公司 | Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same |
| CN101657759A (en) * | 2007-08-01 | 2010-02-24 | 株式会社艾迪科 | Alkali-developable photosensitive resin composition and ss-diketone |
| US20160084859A1 (en) * | 2014-09-19 | 2016-03-24 | Randox Laboratories Limited | Detection of indazole synthetic cannabinoids |
| JP2016124835A (en) * | 2015-01-06 | 2016-07-11 | パナソニックＩｐマネジメント株式会社 | Immunogens, methods for producing antibodies using the same, and monoclonal antibodies |
-
2021
- 2021-11-03 CN CN202111294303.5A patent/CN113999163A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1814301A (en) * | 1996-09-30 | 2006-08-09 | 茨诺瓦研究有限公司 | Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same |
| CN1951502A (en) * | 1996-09-30 | 2007-04-25 | 茨诺瓦研究有限公司 | Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same |
| CN101657759A (en) * | 2007-08-01 | 2010-02-24 | 株式会社艾迪科 | Alkali-developable photosensitive resin composition and ss-diketone |
| US20160084859A1 (en) * | 2014-09-19 | 2016-03-24 | Randox Laboratories Limited | Detection of indazole synthetic cannabinoids |
| JP2016124835A (en) * | 2015-01-06 | 2016-07-11 | パナソニックＩｐマネジメント株式会社 | Immunogens, methods for producing antibodies using the same, and monoclonal antibodies |
Non-Patent Citations (2)
| Title |
|---|
| BRANDON C. PRESLEY等: "Metabolic profiling of synthetic cannabinoid 5F-ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra-high-performance liquid chromatography/high-resolution mass spectrometry", 《RAPID COMMUN MASS SPECTROM.》, pages 1 - 16 * |
| MARIA ANDERSSON等: "Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry", 《RAPID COMMUN. MASS SPECTROM.》, vol. 30, pages 1067 - 1078 * |
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