CN112624956A - Novel process for preparing 3-indolesulfonic acid derivatives - Google Patents
Novel process for preparing 3-indolesulfonic acid derivatives Download PDFInfo
- Publication number
- CN112624956A CN112624956A CN201910951188.0A CN201910951188A CN112624956A CN 112624956 A CN112624956 A CN 112624956A CN 201910951188 A CN201910951188 A CN 201910951188A CN 112624956 A CN112624956 A CN 112624956A
- Authority
- CN
- China
- Prior art keywords
- acid derivative
- indolesulfonic
- acid derivatives
- compound
- indolesulfonic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
Abstract
The invention provides a novel preparation method of a 3-indolsulfonic acid derivative, which realizes a one-pot one-time purification method by changing a technical route, and obtains the 1-position modified 3-indolsulfonic acid derivative with high yield. The method has the advantages of simple operation, mild reaction conditions, cheap and easily obtained reagents, high yield, one-time separation and purification, suitability for mass production, synthesized target products, coupling with carrier protein, expression of specific antibody for recognizing 3-indolsulfonic acid, and provision of material basis and technical route for detecting uremia.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a 3-indolsulfonic acid derivative.
Background
Uremia is the terminal stage of chronic renal failure and is a common clinical syndrome of various end-stage renal diseases. In clinical manifestations of patients, metabolic disorders are generally manifested by accumulation of protein metabolites, including urea, guanidine compounds, creatinine, amines, indoles, phenols, and middle molecular weight substances. Indoles, amines and phenols are toxins produced by the metabolism of uremic bacteria. The indolesulfonic acid compounds are considered to be one of the major causes of uremia, and the content of indolesulfuric acid in serum of patients with chronic renal failure has increased by about 60-fold. Therefore, the determination of the concentration of 3-indolesulfonic acid in serum is of great significance for the examination and diagnosis of uremia. Traditionally, serum uremic toxins have been monitored and analyzed primarily by gas chromatography and high performance liquid chromatography. Although these methods are excellent in both sensitivity and accuracy, they have high requirements for instrumentation and equipment and high dependence on instrumentation and analysis. Therefore, the preparation of the 3-indonesulfonic acid compound with 1-position derivatization of a specific functional group, the coupling of the 3-indonesulfonic acid compound with an antibody and the preparation of a specific detection 3-indonesulfonic acid antibody have important significance.
Structure of 3-indolesulfonic acid derivative:
the technical route previously reported for 3-indolesulfonic acid derivatives:
the preparation of the derivative is carried out by the technical route of the prior patent (JPH 10265457A): the method of three-pot and three-time purification is adopted, the steps are long, and the introduction of amine functional groups adopts a protection-deprotection strategy.
The preparation of the derivative, the reagent used in the prior patent (JPH10265457A) comprises: toxic benzylamine, expensive transition metal reagent palladium carbon and flammable and explosive hazardous gas hydrogen.
The preparation of the derivative is complicated in the process used in the prior patent (JPH 10265457A): the post-treatment is complex, three steps of purification are needed, not only the loss of compounds but also the waste of solvents are caused, and the environmental pollution and the cost are increased; at the same time, the hydrogenation operation is strictly complicated.
The total yield of the derivative in the prior patent (JPH 10265457A): because the polarity of the compounds is large, silica gel columns and palladium carbon are seriously adsorbed, the compound loss is caused by purification, and the total yield in three steps is only 23 percent.
Disclosure of Invention
The technical route for synthesizing the 3-indolesulfonic acid derivative adopted by the invention is as follows:
the specific operation for synthesizing the 3-indolesulfonic acid derivative adopted by the invention is as follows: dissolving 3-indolsulfonic acid potassium salt (50.3mg,0.2 mmol,1.0 equivalent) in 1mL DMF, adding 60% NaH (16mg,0.4mmol,2.0 equivalent) at zero degree, stirring at zero degree for half an hour, adding epichlorohydrin (16 uL, 0.4mmol,2.0 equivalent), stirring at room temperature for three hours, allowing LC-MS detection raw material to disappear (mass spectrum negative ion absorption, M-H ═ 268.0), adding water for quenching, removing DMF under reduced pressure, directly adding ammonia reagent group, sealing for reaction overnight, and allowing LC-MS detection raw material to reactThe material disappeared and the product formed (ms anion M-H285.0), HPLC (C18, 10% -75% MeOH/H)2O) purification to give the title compound (29mg, 51% yield).
The specific operation for synthesizing the 3-indolesulfonic acid derivative adopted by the invention is as follows: dissolving 3-indolsulfonic acid potassium salt (1.06g,4mmol, 1.0 equivalent) in 15mL DMF, adding 60% NaH (320mg,8mmol,2.0 equivalent) at zero degree, stirring at zero degree for half an hour, adding epichlorohydrin (320 uL, 8mmol,2.0 equivalent), stirring at room temperature for three hours later, allowing LC-MS detection raw material to disappear (mass spectrometry negative ion absorption, M-H ═ 268.0), adding water for quenching, removing DMF under reduced pressure, directly adding ammonia reagent group, sealing for reaction overnight, allowing LC-MS detection raw material to disappear, and generating a product (mass spectrometry negative ion M-H ═ 285.0), and performing HPLC (C18, 10% -75% MeOH/H)2O) purification to give the title compound (585mg, 51% yield).
The synthetic method of the 3-indonesulfonic acid derivative has the advantages of simple operation, one-pot method, mild reaction conditions, no toxic reagent, cheap and easily-obtained reagent, high yield of the target product, easy separation and purification, one-time purification and suitability for mass production. The efficient selective synthesis of the 3-indolesulfonic acid derivative has great significance for detecting, diagnosing and treating uremia.
The hydrogen spectrum characterization of the synthesized 3-indole sulfonic acid derivative is as follows:1h NMR (300MHz, DMSO-d6) δ 7.50 (d, J ═ 7.8Hz,1H),7.43(d, J ═ 8.3Hz,1H),7.18(s,1H),7.10(t, J ═ 7.6Hz,1H),6.97(t, J ═ 7.4 Hz,1H),5.76(bs,2H), 4.25-4.05 (m,2H), 4.04-3.91 (m,1H),2.83(dd, J ═ 12.8,3.2Hz,1H), 2.67(dd, J ═ 12.8,9.0Hz,1H) calculated: [ M-H ]]-,C11H13N2O5S285.0, actual negative ion peak: [ M-H ]]-, C11H13N2O5S=285.0
Drawings
FIG. 1 is a hydrogen spectrum of the synthesized 3-indolesulfonic acid derivative.
FIG. 2 is a mass spectrum-negative ion absorption of the synthesized 3-indolesulfonic acid derivative.
Claims (4)
- A novel process for the preparation of 3-indolesulfonic acid derivatives wherein the compound has the structure:(1) the method comprises the following steps: the preparation method of the 3-indole sulfonic acid derivative comprises the following steps: dissolving 3-indole sulfonic acid potassium in DMF, adding 60% NaH at zero, slowly heating to room temperature, stirring for half an hour, adding epoxy chloropropane, stirring for three hours at room temperature, removing the LC-MS detection raw material, performing mass spectrum negative ion, adding water for quenching, removing the DMF under reduced pressure, directly adding an ammonia reagent group, performing sealing reaction overnight, removing the LC-MS detection raw material, performing mass spectrum negative ion, and performing HPLC purification to obtain the target compound.
- 2. The process for preparing 3-indolesulfonic acid derivatives as claimed in claim 1, wherein NH is the only ammonia reagent3Methanol, NH3Ethanol, NH3The nucleophilic reagent is/1, 4-dioxane or ammonia water.
- 3. The process for producing a 3-indolesulfonic acid derivative according to claim 1, characterized in that: compound 1/epichlorohydrin/NH3The nucleophile used was a solution of amine in methanol at a molar ratio of (1/1.5/10).
- 4. The process for producing a 3-indolesulfonic acid derivative according to claim 1, characterized in that: adopts a one-pot one-time purification method.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910951188.0A CN112624956A (en) | 2019-10-08 | 2019-10-08 | Novel process for preparing 3-indolesulfonic acid derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910951188.0A CN112624956A (en) | 2019-10-08 | 2019-10-08 | Novel process for preparing 3-indolesulfonic acid derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112624956A true CN112624956A (en) | 2021-04-09 |
Family
ID=75283257
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910951188.0A Pending CN112624956A (en) | 2019-10-08 | 2019-10-08 | Novel process for preparing 3-indolesulfonic acid derivatives |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112624956A (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10265457A (en) * | 1997-03-19 | 1998-10-06 | Kureha Chem Ind Co Ltd | Indoxyl sulfate derivative, antigen, antibody and detection of indoxyl sulfate using the same |
CN101434571A (en) * | 2007-11-13 | 2009-05-20 | 杭州容立医药科技有限公司 | Cycloalkano [1,2-b] indole sulfonic acid amide, and method for synthesizing isomer or salt thereof |
CN102272128A (en) * | 2008-11-06 | 2011-12-07 | 弗特克斯药品有限公司 | Modulators of atp-binding cassette transporters |
US20120035346A1 (en) * | 2009-01-15 | 2012-02-09 | Terpetschnig Ewald A | Luminescent compounds |
CN105348268A (en) * | 2015-09-24 | 2016-02-24 | 四川大学 | Substituted carbazole-indole sulfonate derivative, and preparation method therefor and use thereof |
CN106946758A (en) * | 2017-03-07 | 2017-07-14 | 丽水学院 | A kind of synthetic method of 3 (trifluoroacetyl) indole derivativeses |
-
2019
- 2019-10-08 CN CN201910951188.0A patent/CN112624956A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10265457A (en) * | 1997-03-19 | 1998-10-06 | Kureha Chem Ind Co Ltd | Indoxyl sulfate derivative, antigen, antibody and detection of indoxyl sulfate using the same |
CN101434571A (en) * | 2007-11-13 | 2009-05-20 | 杭州容立医药科技有限公司 | Cycloalkano [1,2-b] indole sulfonic acid amide, and method for synthesizing isomer or salt thereof |
CN102272128A (en) * | 2008-11-06 | 2011-12-07 | 弗特克斯药品有限公司 | Modulators of atp-binding cassette transporters |
US20120035346A1 (en) * | 2009-01-15 | 2012-02-09 | Terpetschnig Ewald A | Luminescent compounds |
CN105348268A (en) * | 2015-09-24 | 2016-02-24 | 四川大学 | Substituted carbazole-indole sulfonate derivative, and preparation method therefor and use thereof |
CN106946758A (en) * | 2017-03-07 | 2017-07-14 | 丽水学院 | A kind of synthetic method of 3 (trifluoroacetyl) indole derivativeses |
Non-Patent Citations (2)
Title |
---|
YONG-LIANG ZHAO,等: "Identification of Racemic and Chiral Carbazole Derivatives Containing an Isopropanolamine Linker as Prospective Surrogates against Plant Pathogenic Bacteria: In Vitro and In Vivo Assays and Quantitative Proteomics", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
花林: "Fischer法合成吲哚磺酸类化合物的研究", 《中国优秀博硕士学位论文全文数据库(硕士) 工程科技Ⅰ辑》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Foo et al. | Total Synthesis–Guided Structure Elucidation of (+)-Psychotetramine | |
CN109735328B (en) | Fluorescent probe for detecting intracellular hydrogen sulfide and preparation method and application thereof | |
WO2012007585A1 (en) | Derivatization of oligosaccharides | |
CN106749884B (en) | A kind of phosphorylation peptide gathering material and the preparation method and application thereof | |
CN109928937A (en) | Water-soluble column [n] aromatic hydrocarbons and its synthetic method | |
CN103713057B (en) | Method for degrading heparan sulfate and detecting heparan sulfate disaccharide composition | |
CN112624956A (en) | Novel process for preparing 3-indolesulfonic acid derivatives | |
CN110343734A (en) | A kind of L-glufosinate-ammonium chemical-enzymatic production method | |
TW201536755A (en) | Compounds and methods for analysis and synthesis of saccharide compounds | |
CN104826618B (en) | Aminodiol hydrophilic chromatography stationary phase and preparation method thereof | |
CN104130195A (en) | Synthetic method for carbendazim hapten | |
CN106946926A (en) | One kind have multiple tooth ammonia carboxylic class dimer chelating agent and preparation method thereof, using and separating medium | |
Zhu et al. | Determination of biogenic amines in alcoholic beverages using a novel fluorogenic compound as derivatizing reagent | |
CN114486835B (en) | Rapid detection method for tryptophan in food by using cholesteric chiral molecular clamp | |
Ito et al. | An Improved Procedure for Aryne Generation from o‐Triazenylarylboronic Acids through One‐Pot Boronate Formation/Silica Gel Treatment | |
CN103940936B (en) | Detection method of 4alpha-hydroxy-L-proline and trace L-proline in 4alpha-hydroxy-L-proline | |
CN113402352A (en) | Stable isotope amino compound labeling reagent and synthetic method and application thereof | |
CN105949250A (en) | Preparation method of alpha-2,3-sialyllactulose | |
CN108018323B (en) | Preparation method of adenylyl succinic acid or salt | |
CN114113357A (en) | Etimicin starting material gentamicin C1aIs detected by | |
Qin et al. | Detection and separation of chito/chitin oligosaccharides | |
Komarova et al. | Water-dependent reduction of carbohydrate azides by dithiothreitol | |
Baer et al. | Bisglycosidylamines, a new class of amino sugars | |
CN111205213A (en) | Chemical cross-linking agent and preparation and application thereof | |
Xie et al. | The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210409 |
|
RJ01 | Rejection of invention patent application after publication |