CH283634A - Process for the preparation of a peptide-like derivative of the lysergic acid series. - Google Patents
Process for the preparation of a peptide-like derivative of the lysergic acid series.Info
- Publication number
- CH283634A CH283634A CH283634DA CH283634A CH 283634 A CH283634 A CH 283634A CH 283634D A CH283634D A CH 283634DA CH 283634 A CH283634 A CH 283634A
- Authority
- CH
- Switzerland
- Prior art keywords
- methyl ester
- histidine
- preparation
- lysergyl
- lysergic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- ZAGRKAFMISFKIO-QMTHXVAHSA-N lysergic acid Chemical class C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-QMTHXVAHSA-N 0.000 title description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- NCIHPOHJJSIWSC-QMTHXVAHSA-N (6ar,9r)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl azide Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(=O)N=[N+]=[N-])=C3C2=CNC3=C1 NCIHPOHJJSIWSC-QMTHXVAHSA-N 0.000 claims description 2
- 238000000354 decomposition reaction Methods 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 239000013067 intermediate product Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- NCIHPOHJJSIWSC-IINYFYTJSA-N (6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carbonyl azide Chemical compound C(=O)([C@@H]1CN(C)[C@@H]2CC3=CNC4=CC=CC(C2=C1)=C34)N=[N+]=[N-] NCIHPOHJJSIWSC-IINYFYTJSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- GSWAOPJLTADLTN-UHFFFAOYSA-N oxidanimine Chemical compound [O-][NH3+] GSWAOPJLTADLTN-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
Verfahren zur Darstellung eines peptidartigen Derivates der Lysergsäure-Reihe. Das vorliegende Patent betrifft ein Ver fahren zur Darstellung von d - Lysergyl-1- histidin-rnethylester,welches dadurch gekenn zeichnet ist., dass nian d-Lysergsätire-azid mit 1-Histidin-inethylester kondensiert.
<I>Beispiel:</I> Eine Lösung von 1,0 g d-Isolysergsäure- azid in 120 em3 Äther mischt man mit einer bösung von 1,16 g 1-Ilistidin-iriethylester (ent sprechend 2 Äquivalenten, auf das Azid be zogen) in einem Gemisch von 50 em3 Äther und 10 em3 Isopropylalkoliol, worin sich das d-Isolysergsäure-azid bis zu einem Gleichge wicht in d-Lysergsäure-azid umlagert., und lässt bei 20" C 12 Stunden stehen.
Nachdem man den stickstoffwasserstoff- sauren Histidiri-methylester durch Ausschüt teln mit dreimal 20 em3 Wasser entfernt. hat, dampft man die mit Natriumsulfat getrock nete Reaktionslösung unter Vakuum ein. Das Rohprodukt wird ehromatographiseh zerlegt. Dazu wird der Rückstand in wenig Chloroform gelöst und an eine Säule aus 300g Ahimi- niumoxyd aufgezogen. Beim Entwickeln mit dem gleichen Lösungsmittel werden wenig dunkle Nebenprodukte ins Filtrat gewaschen.
Beim Weiterentwickeln mit Chloroform, das 1% Alkohol enthält, beobachtet man im UV- Licht die Aufspaltung der breiten blauleuch tenden Hauptzone in zwei getrennte Bänder. Aus der besser haftenden Zone lassen sich 0,3 bis 0,5 g des Lysergsäure-Deriv ates eluie- ren. Der d-Ly sergyl-l-histidin-metliylester ist in Alkohol, Aceton und Chloroform leicht, in Benzol schwerlöslich.
Er kristallisiert aus keinem dieser Lösungsmittel.
Beim Neutralisieren der alkoholischen Lö sung der Base mit alkoholischer Salzsäure, wobei zwei Äquivalente Sä Lire verbraucht wer den, erhält man das Dichlorhydrat, das auf Zusatz von Äther auskristallisiert. Das d- Ly ser gyl-l-Iristidin -methylester-diclilorhy drat, C231-I2503N5 . 2 HCI, schmilzt unscharf bei 1.90" C (korr.) unter Zersetzung. Das Salz ist in Wasser ziemlich leicht. löslich.
[all' = +13 (e = 0,25 in Methanol).
Process for the preparation of a peptide-like derivative of the lysergic acid series. The present patent relates to a process for the preparation of d-lysergyl-1-histidine-methyl ester, which is characterized in that nian d-lysergyl-azide condenses with 1-histidine-methyl ester.
<I> Example: </I> A solution of 1.0 g of d-isolysergic acid azide in 120 em3 ether is mixed with a solution of 1.16 g of 1-ilistidine-iriethyl ester (corresponding to 2 equivalents, based on the azide pulled) in a mixture of 50 em3 ether and 10 em3 isopropyl alcohol, in which the d-isolysergic acid azide is rearranged to an equilibrium in d-lysergic acid azide., and left at 20 "C for 12 hours.
After the histidiral methyl ester is removed by shaking with three times 20 cubic meters of water. the reaction solution getrock designated with sodium sulfate is evaporated under vacuum. The crude product is broken down by chromatography. To do this, the residue is dissolved in a little chloroform and drawn up on a column of 300 g ammonium oxide. When developing with the same solvent, a few dark by-products are washed into the filtrate.
When developing further with chloroform, which contains 1% alcohol, the splitting of the broad blue luminous main zone into two separate bands can be observed in UV light. 0.3 to 0.5 g of the lysergic acid derivative can be eluted from the better adhering zone. The d-lysergyl-1-histidine methyl ester is easily soluble in alcohol, acetone and chloroform, and is sparingly soluble in benzene.
It does not crystallize from any of these solvents.
When the alcoholic solution of the base is neutralized with alcoholic hydrochloric acid, whereby two equivalents of acid are consumed, the dichlorohydrate is obtained, which crystallizes out on addition of ether. The d-ly ser gyl-l-iristidine methyl ester diclilorhydrate, C231-I2503N5. 2 HCI, melts indistinctly at 1.90 "C (corr.) With decomposition. The salt is quite easily soluble in water.
[all '= +13 (e = 0.25 in methanol).
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH283634T | 1948-09-17 | ||
| CH269795T | 1948-09-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH283634A true CH283634A (en) | 1952-06-15 |
Family
ID=25731128
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH283634D CH283634A (en) | 1948-09-17 | 1948-09-17 | Process for the preparation of a peptide-like derivative of the lysergic acid series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH283634A (en) |
-
1948
- 1948-09-17 CH CH283634D patent/CH283634A/en unknown
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