DE497097C - Process for the preparation of amino acid amides - Google Patents
Process for the preparation of amino acid amidesInfo
- Publication number
- DE497097C DE497097C DEC38112D DEC0038112D DE497097C DE 497097 C DE497097 C DE 497097C DE C38112 D DEC38112 D DE C38112D DE C0038112 D DEC0038112 D DE C0038112D DE 497097 C DE497097 C DE 497097C
- Authority
- DE
- Germany
- Prior art keywords
- parts
- amino acid
- preparation
- acid amides
- iodophosphonium
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 5
- 150000001413 amino acids Chemical class 0.000 title claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 7
- QAXHWUAAPKHMGA-UHFFFAOYSA-N iodophosphane Chemical compound IP QAXHWUAAPKHMGA-UHFFFAOYSA-N 0.000 description 7
- -1 B. hydrohalic acids Chemical class 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 2
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 108010008488 Glycylglycine Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940043257 glycylglycine Drugs 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PZMLXPJGXAXJGQ-UHFFFAOYSA-N iodophosphonous acid Chemical compound OP(O)I PZMLXPJGXAXJGQ-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/08—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents
- C07K1/086—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/08—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents
- C07K1/082—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents containing phosphorus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/08—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents
- C07K1/088—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using activating agents containing other elements, e.g. B, Si, As
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Darstellung von Aminosäureamiden Unterwirft man Säureamide der Behandlung mit Mineralsäuren, z. B. Halogenwasserstoffsäuren, so tritt unter Rückbildung von Säure und Atnmonial;derivat Hydrolyse auf, eine Reaktion, die praktisch zur Hydrolyse von Eiweißkörpern Verwendung findet. Infolge der Instabilität der Säureamidbindung ist man nicht in der Lage, Acylderivate der Sättreamide von ihrem Acyl zu befreien, ohne auch die Säureamidbindung zu lösen. Dies gilt für jede Art Acyle, aliphatische, aromatische, halogensubstituierte oder Sttlfonylderiv ate.Process for the preparation of amino acid amides One submits to acid amides treatment with mineral acids, e.g. B. hydrohalic acids, it occurs below Regression of acid and atmospheric; derivative hydrolysis on, a reaction which is practical for the hydrolysis of protein bodies is used. As a result of the instability of the Acid amide bond one is unable to obtain acyl derivatives of the saturation side from their To free acyl without also breaking the acid amide bond. This applies to every species Acyl, aliphatic, aromatic, halogen-substituted or Sttlfonylderiv ate.
Aus den Arbeiten . Emil Fischers (Band 48 [igi5] S. 368) ist bekannt, daß es durch Reduktion mit konzentriertem Jodwasserstoff gelingt, sulfonylierte Aminogruppen von dem Substituenten zu befreien.From the work. Emil Fischers (Volume 48 [igi5] p. 368) is known that it succeeds by reduction with concentrated hydrogen iodide, sulfonylated To free amino groups from the substituent.
Es wurde nun gefunden, daß Säureamidbindungen völlig beständig gegen jodwasserstoffsäure sind, während sie durch Chlor-und Bromwasserstoffsäure hydrolysiert werden. 'Man ist so in die Lage versetzt, aus sulfonylierten Säureatnidderivaten ohne Lösung der Säureamidbindung den Acylrest zu entfernen. Auf diese Weise kann man zu Arzneimitteln gelangen, die bisher der Synthese nicht zugänglich sind.It has now been found that acid amide bonds are completely resistant to are hydroiodic acid while hydrolyzed by hydrochloric and hydrobromic acid will. 'One is thus able to make sulfonylated acid nide derivatives to remove the acyl residue without dissolving the acid amide bond. That way you can one arrives at drugs that have not been synthesized up to now.
Um an Jodwasserstoff zu sparen, setzt man zweckmäßig jodphosphonium zu. Beispiel 6 Teile Toluolsulfogly cylglycin (H o p p e -S e y 1 e r, Zeitschr. f. physiol. Chemie, Band 154, S. 2io) werden mit 6o Teilen Jodwasserstoff (r,96) und 5 Teilen Jodphosphonium auf 55° unter Schütteln etwa 5bis6 Stunden erhitzt. Das Reaktionsprodukt wird nach Entfernen des Tolylmercaptans vom Jod befreit und eingedampft. Das Glycylglycin wird in nahezu theoretischer Ausbeute gewonnen. Beispiel e 87 Teile Toluolsulfoglycyl - d, i - alanin (Hoppe - S e y 1 e r , Zeitschr. f. physiol. Chemie, Band 154, S. 211) mit iooo Teilen Jodwasserstoff und 8o Teilen Jodphosphonium auf die gleiche Weise behandelt, geben nach dem Aufarbeiten 9o Prozent der Theorie Glycyl-d, i-alanin. Beispiel 3 45 Teile Toluolsulfoglycy l - d, i - leucin (Hoppe - S e y 1 e r , Zeitschr. f. phy siol. Chemie, Band 154, S. 212) mit 4o Teilen Jodphosphonium in 5oo Teilen Jodwasserstoff sättre geben etwa 9o Prozent der Theorie Glycyl-d, i-leucin. Beispiel 8 Teile -Toluolsulfod - d - alanyl - i - leucin (H o p p e - S e v 1 e r , Zeitschr. f. physiol. Chemie, Band y1 5q., S. 21q.) mit 8o Teilen Jodwasserstoff und 8 Teilen Jodphosphoniüm umgesetzt, geben das d-Alanyl-i-leucin. -Nach der gleichen Methode lassen sich cl, i-Leucylglycin, d, 1 Alanylglycin und andere Derivate herstellen. Statt von Toluolsulfoverbindungen kann man auch von Benzols.ulfov erhindungen ausgehen, doch ist die Toluolsulfogruppe aus wirtschaftlichen Gründen vorzuziehen. Beispiel s 4,6 Teile Äthansulfoglycylglycin (gewonnen durch Umsetzen von Äthansulfochlori,cl mit Glykokoll, Umwandlung des Äthansulfoglycins in das Säurechlorid mittels Thionylchlorids und Umsetzen des Säurechlorids mit Glykokoll) werden mit 6o Teilen Jodwasserstoff (1,g6)- und 5 Teilen Jodpliosphonitun schwach unter Schütteln einige Stunden erwärmt. Man erhält das GlvcN>1-gllycin in über goprozentiger Ausbeute. w Der Zusatz von Jodphosphonium kann unterbleiben, wenn keine Gefahr besteht, daß das bei der Reaktion frei werdende Jod unter den Reaktionsbedingungen die Base selbst verändert. . Statt des Jodphosphoniums kann mit dem gleichen Erfolg auch roter Phosphor zugesetzt werden. Die Reaktion läuft auch ohne diesen "Zusatz in der gleichen Weise ab.In order to save on hydrogen iodide, it is advisable to add iodophosphonium. EXAMPLE 6 parts of toluenesulfoglycylglycine (Hoppe-Seyer, Zeitschr. F. Physiol. Chemie, Volume 154, p. 2io) are mixed with 60 parts of hydrogen iodide (r, 96) and 5 parts of iodophosphonium to 55 ° with shaking about 5 to 6 parts Heated for hours. After removing the tolyl mercaptan, the reaction product is freed from iodine and evaporated. The glycylglycine is obtained in almost theoretical yield. Example e 87 parts of toluenesulfoglycyl-d, i-alanine (Hoppe-S ey 1 er, Zeitschr. F. Physiol. Chemie, Volume 154, p. 211) treated in the same way with 1000 parts of hydrogen iodide and 80 parts of iodophosphonium give way working up 90 percent of the theory of glycyl-d, i-alanine. Example 3 45 parts of toluenesulfoglycy 1 - d, i - leucine (Hoppe - S ey 1 er, Zeitschr. F. Phy siol. Chemie, Volume 154, p. 212) with 40 parts of iodophosphonium in 500 parts of hydrogen iodide give about 90 percent of the saturation Theory glycyl-d, i-leucine. Example 8 parts of toluenesulfod-d-alanyl-i-leucine (Hoppe-S ev 1 er, Zeitschr. F. Physiol. Chemie, Volume y1 5q., P. 21q.) Reacted with 80 parts of hydrogen iodide and 8 parts of iodophosphonium, give the d-alanyl-i-leucine. -The same method can be used to prepare cl, i-leucylglycine, d, 1-alanylglycine and other derivatives. Instead of toluene sulpho compounds, one can also start from benzene sulpho compounds, but the toluene sulpho group is to be preferred for economic reasons. Example s 4.6 parts of ethanesulphoglycylglycine (obtained by reacting ethanesulphochlori, cl with glycocoll, converting ethanesulphoglycine into the acid chloride by means of thionyl chloride and reacting the acid chloride with glycocoll) are weakly reduced with 60 parts of hydrogen iodide (1, g6) and 5 parts of iodophosphonite Shake heated for a few hours. The GlvcN> 1-gllycine is obtained in over 100 percent yield. w The addition of iodophosphonium can be omitted if there is no risk that the iodine released during the reaction will change the base itself under the reaction conditions. . Instead of iodophosphonium, red phosphorus can also be added with the same success. The reaction proceeds in the same way without this addition.
Die nach dem vorliegenden Verfahren dargestellten Aminosäureamide sollen in der medizinischen Diagnostik sowie zur Her stellung neuer Heilmittel Verwendung finden.The amino acid amides prepared by the present process are to be used in medical diagnostics and for the manufacture of new remedies Find.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC38112D DE497097C (en) | 1926-04-14 | 1926-04-14 | Process for the preparation of amino acid amides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC38112D DE497097C (en) | 1926-04-14 | 1926-04-14 | Process for the preparation of amino acid amides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE497097C true DE497097C (en) | 1930-05-02 |
Family
ID=7023143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEC38112D Expired DE497097C (en) | 1926-04-14 | 1926-04-14 | Process for the preparation of amino acid amides |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE497097C (en) |
-
1926
- 1926-04-14 DE DEC38112D patent/DE497097C/en not_active Expired
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