DE2021706C2 - Verfahren zur Herstellung von peptidartigen Mutterkornalkaloiden - Google Patents
Verfahren zur Herstellung von peptidartigen MutterkornalkaloidenInfo
- Publication number
- DE2021706C2 DE2021706C2 DE19702021706 DE2021706A DE2021706C2 DE 2021706 C2 DE2021706 C2 DE 2021706C2 DE 19702021706 DE19702021706 DE 19702021706 DE 2021706 A DE2021706 A DE 2021706A DE 2021706 C2 DE2021706 C2 DE 2021706C2
- Authority
- DE
- Germany
- Prior art keywords
- acid
- general formula
- mmol
- compounds
- mixture
- 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 22
- 230000008569 process Effects 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title description 7
- 229960003133 ergot alkaloid Drugs 0.000 title description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 26
- 150000008064 anhydrides Chemical class 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000003791 organic solvent mixture Substances 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- ZAGRKAFMISFKIO-UHFFFAOYSA-N Isolysergic acid Natural products C1=CC(C2=CC(CN(C2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-UHFFFAOYSA-N 0.000 description 22
- XCGSFFUVFURLIX-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)=C1)C)C1=CC=CC=C1 XCGSFFUVFURLIX-VFGNJEKYSA-N 0.000 description 16
- 229960004943 ergotamine Drugs 0.000 description 16
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 16
- ZAGRKAFMISFKIO-QMTHXVAHSA-N lysergic acid Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-QMTHXVAHSA-N 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- ZAGRKAFMISFKIO-IINYFYTJSA-N (6ar,9s)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC(C2=C[C@@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-IINYFYTJSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HYHBKLWDTGTBME-UHFFFAOYSA-N pyrazin-1-ium;chloride Chemical compound Cl.C1=CN=CC=N1 HYHBKLWDTGTBME-UHFFFAOYSA-N 0.000 description 6
- BOLCFGMGGWCOOE-UHFFFAOYSA-N Ergostine Natural products N12C(=O)C(CC)(NC(=O)C3C=C4C=5C=CC=C6NC=C(C=56)CC4N(C)C3)OC2(O)C2CCCN2C(=O)C1CC1=CC=CC=C1 BOLCFGMGGWCOOE-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- ORBSYPFBZQJNJE-MPKXVKKWSA-N (6ar,9r,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC([C@H]2C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ORBSYPFBZQJNJE-MPKXVKKWSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- -1 B. as Hydrochloride Chemical class 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229960004704 dihydroergotamine Drugs 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 229930015720 peptide alkaloid Natural products 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910021653 sulphate ion Inorganic materials 0.000 description 3
- VAPRZIDWFJHKLR-BWTUWSSMSA-N (6ar,9r)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid;hydrate Chemical compound O.C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 VAPRZIDWFJHKLR-BWTUWSSMSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- SEALOBQTUQIVGU-QNIJNHAOSA-N dihydroergocornine Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)C)C(C)C)=C3C2=CNC3=C1 SEALOBQTUQIVGU-QNIJNHAOSA-N 0.000 description 2
- 229960004290 dihydroergocornine Drugs 0.000 description 2
- DEQITUUQPICUMR-HJPBWRTMSA-N dihydroergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C(C)C)C1=CC=CC=C1 DEQITUUQPICUMR-HJPBWRTMSA-N 0.000 description 2
- 229960004318 dihydroergocristine Drugs 0.000 description 2
- LUZRJRNZXALNLM-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C)C1=CC=CC=C1 LUZRJRNZXALNLM-JGRZULCMSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- HEFIYUQVAZFDEE-MKTPKCENSA-N ergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@@H]1C=C2C=3C=CC=C4NC=C(C=34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 HEFIYUQVAZFDEE-MKTPKCENSA-N 0.000 description 2
- HEFIYUQVAZFDEE-UHFFFAOYSA-N ergocristinine Natural products N12C(=O)C(C(C)C)(NC(=O)C3C=C4C=5C=CC=C6NC=C(C=56)CC4N(C)C3)OC2(O)C2CCCN2C(=O)C1CC1=CC=CC=C1 HEFIYUQVAZFDEE-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 150000007530 organic bases Chemical group 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000124224 Claviceps paspali Species 0.000 description 1
- UJYGDMFEEDNVBF-UHFFFAOYSA-N Ergocorninine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)C(C)C)C(C)C)C2)=C3C2=CNC3=C1 UJYGDMFEEDNVBF-UHFFFAOYSA-N 0.000 description 1
- XWTYUTWHTOOWSS-WTDBAMAISA-N Ergonine Chemical compound CC[C@@]1(NC(=O)[C@H]2CN(C)C3CC4=CNC5=CC=CC(=C45)C3=C2)O[C@@]2(O)C3CCCN3C(=O)[C@H](C(C)C)N2C1=O XWTYUTWHTOOWSS-WTDBAMAISA-N 0.000 description 1
- XWTYUTWHTOOWSS-MWBPXRJMSA-N Ergonine Natural products O=C(N[C@@]1(CC)C(=O)N2[C@H](C(C)C)C(=O)N3[C@@H]([C@]2(O)O1)CCC3)[C@@H]1C=C2[C@H](N(C)C1)Cc1c3c([nH]c1)cccc23 XWTYUTWHTOOWSS-MWBPXRJMSA-N 0.000 description 1
- JFRCRHHCXKEHBW-UHFFFAOYSA-N Ergoptin Natural products O1C2(O)C3CCCN3C(=O)C(CC(C)C)N2C(=O)C1(CC)NC(=O)C(CN(C)C1C2)C=C1C1=C3C2=CNC3=CC=C1 JFRCRHHCXKEHBW-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- YDOTUXAWKBPQJW-UHFFFAOYSA-N alpha-Ergocryptinine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-UHFFFAOYSA-N 0.000 description 1
- YDOTUXAWKBPQJW-NSLWYYNWSA-N alpha-ergocryptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-NSLWYYNWSA-N 0.000 description 1
- 229950001817 alpha-ergocryptine Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- PBUNVLRHZGSROC-VTIMJTGVSA-N dihydro-alpha-ergocryptine Chemical compound C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)CC(C)C)C(C)C)=C3C2=CNC3=C1 PBUNVLRHZGSROC-VTIMJTGVSA-N 0.000 description 1
- QKMRPKVJXKAXHL-OLNIQZLRSA-N dihydroergonine Chemical compound C([C@H]1[C@]2(O)O3)CCN1C(=O)[C@H](C(C)C)N2C(=O)[C@]3(CC)NC(=O)[C@H]1CN(C)[C@H](CC=2C3=C4C=CC=C3NC=2)[C@@H]4C1 QKMRPKVJXKAXHL-OLNIQZLRSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- UJYGDMFEEDNVBF-OGGGUQDZSA-N ergocornine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)C(C)C)C(C)C)C2)=C3C2=CNC3=C1 UJYGDMFEEDNVBF-OGGGUQDZSA-N 0.000 description 1
- JFRCRHHCXKEHBW-YKAZNSBZSA-N ergoptin Chemical compound C([C@H]1[C@]2(O)O3)CCN1C(=O)[C@@H](CC(C)C)N2C(=O)[C@]3(CC)NC(=O)[C@@H](CN(C)[C@@H]1C2)C=C1C1=C3C2=CNC3=CC=C1 JFRCRHHCXKEHBW-YKAZNSBZSA-N 0.000 description 1
- BGHDUTQZGWOQIA-RKUMIMICSA-N ergovaline Natural products O=C(N[C@@]1(C)C(=O)N2[C@H](C(C)C)C(=O)N3[C@@H]([C@]2(O)O1)CCC3)[C@@H]1C=C2[C@H](N(C)C1)Cc1c3c([nH]c1)cccc23 BGHDUTQZGWOQIA-RKUMIMICSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- TUNQTZDLMCRIIZ-UHFFFAOYSA-N pyrrolo[1,2-a]pyrazine hydrochloride Chemical compound Cl.C1=NC=CN2C=CC=C21 TUNQTZDLMCRIIZ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH691269A CH530374A (de) | 1969-05-06 | 1969-05-06 | Neues Verfahren zur Herstellung von Mutterkornpeptidalkaloiden |
| CH1011869 | 1969-07-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2021706A1 DE2021706A1 (de) | 1970-11-19 |
| DE2021706C2 true DE2021706C2 (de) | 1983-08-25 |
Family
ID=25700377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702021706 Expired DE2021706C2 (de) | 1969-05-06 | 1970-05-04 | Verfahren zur Herstellung von peptidartigen Mutterkornalkaloiden |
Country Status (10)
| Country | Link |
|---|---|
| BE (1) | BE749920A (is") |
| CS (1) | CS152357B2 (is") |
| DE (1) | DE2021706C2 (is") |
| DK (1) | DK132029C (is") |
| FR (1) | FR2047237A5 (is") |
| GB (1) | GB1301346A (is") |
| HU (1) | HU162310B (is") |
| NL (1) | NL167438C (is") |
| PL (1) | PL80563B1 (is") |
| SE (1) | SE382634B (is") |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH601321A5 (is") * | 1975-01-06 | 1978-07-14 | Sandoz Ag |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2736728A (en) * | 1954-12-06 | 1956-02-28 | Lilly Co Eli | Preparation of lysergic acid amides |
| US2997470A (en) * | 1956-03-05 | 1961-08-22 | Lilly Co Eli | Lysergic acid amides |
-
1970
- 1970-04-17 GB GB1301346D patent/GB1301346A/en not_active Expired
- 1970-04-27 NL NL7006077A patent/NL167438C/xx not_active IP Right Cessation
- 1970-05-04 SE SE607570A patent/SE382634B/xx unknown
- 1970-05-04 DE DE19702021706 patent/DE2021706C2/de not_active Expired
- 1970-05-04 FR FR7016159A patent/FR2047237A5/fr not_active Expired
- 1970-05-04 PL PL14041270A patent/PL80563B1/pl unknown
- 1970-05-04 CS CS307570A patent/CS152357B2/cs unknown
- 1970-05-04 BE BE749920D patent/BE749920A/xx not_active IP Right Cessation
- 1970-05-05 HU HUSA002084 patent/HU162310B/hu unknown
- 1970-05-05 DK DK229470A patent/DK132029C/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE382634B (sv) | 1976-02-09 |
| DK132029B (da) | 1975-10-13 |
| GB1301346A (is") | 1972-12-29 |
| NL167438C (nl) | 1981-12-16 |
| CS152357B2 (is") | 1973-12-19 |
| BE749920A (fr) | 1970-11-04 |
| NL167438B (nl) | 1981-07-16 |
| DK132029C (da) | 1976-03-01 |
| PL80563B1 (is") | 1975-08-30 |
| DE2021706A1 (de) | 1970-11-19 |
| FR2047237A5 (is") | 1971-03-12 |
| NL7006077A (is") | 1970-11-10 |
| HU162310B (is") | 1973-01-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8125 | Change of the main classification |
Ipc: C07D519/02 |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition |