CA1051879A - Synthese de l'elymoclavine et de ses derives - Google Patents

Synthese de l'elymoclavine et de ses derives

Info

Publication number: CA1051879A
Authority: CA; Canada
Prior art keywords: methyl; ergolene; methoxy; formula; formyl
Prior art date: 1974-08-02
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

Application number

CA228,474A

Other languages

English (en)

Other versions

CA228474S (en

Inventor

Edmund C. Kornfeld

Nicholas J. Bach

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

Priority date (The priority date 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 date listed.)

1974-08-02

Filing date

1975-06-04

Publication date

1979-04-03

1974-08-02 Priority claimed from US494149A external-priority patent/US3923812A/en

1974-08-02 Priority claimed from US494147A external-priority patent/US3929796A/en

1975-06-04 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1979-04-03 Application granted granted Critical

1979-04-03 Publication of CA1051879A publication Critical patent/CA1051879A/fr

Status Expired legal-status Critical Current

Links

DAVNRFCJMIONPO-UHFFFAOYSA-N elymoclavine Natural products C1=CC(C2C=C(CO)CN(C2C2)C)=C3C2=CNC3=C1 DAVNRFCJMIONPO-UHFFFAOYSA-N 0.000 title abstract description 16
IAOSEBXZNXDPEE-UKRRQHHQSA-N elymoclavine Chemical compound C1=CC=C2[C@H]3C=C(CO)CN(C)[C@@H]3CC3=CN=C1[C]32 IAOSEBXZNXDPEE-UKRRQHHQSA-N 0.000 title abstract description 15
230000015572 biosynthetic process Effects 0.000 title abstract description 10
238000003786 synthesis reaction Methods 0.000 title abstract description 10
238000000034 method Methods 0.000 claims abstract description 18
150000001875 compounds Chemical class 0.000 claims description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
239000007800 oxidant agent Substances 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
108010057464 Prolactin Proteins 0.000 abstract description 19
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229940097325 prolactin Drugs 0.000 abstract description 19
230000002401 inhibitory effect Effects 0.000 abstract description 4
229930014626 natural product Natural products 0.000 abstract description 4
230000003647 oxidation Effects 0.000 abstract description 3
238000007254 oxidation reaction Methods 0.000 abstract description 3
230000003389 potentiating effect Effects 0.000 abstract description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
241000700159 Rattus Species 0.000 description 12
239000000243 solution Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
229960001701 chloroform Drugs 0.000 description 8
239000000203 mixture Substances 0.000 description 8
150000001299 aldehydes Chemical class 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
-1 methergine Natural products 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
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229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
230000028327 secretion Effects 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
239000002026 chloroform extract Substances 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
239000010410 layer Substances 0.000 description 4
229930015720 peptide alkaloid Natural products 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000011282 treatment Methods 0.000 description 4
KCHBNRCSCHMJFD-ZBFHGGJFSA-N (6ar,9s)-9-(hydroxymethyl)-7-methyl-4,6,6a,8-tetrahydroindolo[4,3-fg]quinoline-9-ol Chemical compound C1=CC(C2=C[C@@](O)(CO)CN([C@@H]2C2)C)=C3C2=CNC3=C1 KCHBNRCSCHMJFD-ZBFHGGJFSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
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 3
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HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
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238000004587 chromatography analysis Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
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PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
230000001590 oxidative effect Effects 0.000 description 3
150000003138 primary alcohols Chemical class 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
VRGCYEIGVVTZCC-UHFFFAOYSA-N 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione Chemical compound ClC1=C(Cl)C(=O)C(=O)C(Cl)=C1Cl VRGCYEIGVVTZCC-UHFFFAOYSA-N 0.000 description 2
ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 2
XJOOMMHNYOJWCZ-UHFFFAOYSA-N Agroclavine Natural products C1=CC(C2C=C(C)CN(C2C2)C)=C3C2=CNC3=C1 XJOOMMHNYOJWCZ-UHFFFAOYSA-N 0.000 description 2
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206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
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LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
UPKBEIIDYOMDQW-UKRRQHHQSA-N agroclavine Chemical compound C1=CC=C2[C@H]3C=C(C)CN(C)[C@@H]3CC3=CN=C1[C]32 UPKBEIIDYOMDQW-UKRRQHHQSA-N 0.000 description 2
229950001817 alpha-ergocryptine Drugs 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
XQUUDUKVJKNJNP-OGGGUQDZSA-N ergocornine Chemical compound C([C@H]1N(C)C2)C([C]34)=CN=C4C=CC=C3C1=C[C@H]2C(=O)N[C@@]1(C(C)C)C(=O)N2[C@@H](C(C)C)C(=O)N3CCC[C@H]3[C@]2(O)O1 XQUUDUKVJKNJNP-OGGGUQDZSA-N 0.000 description 2
OFKDAAIKGIBASY-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(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
229960004943 ergotamine Drugs 0.000 description 2
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 2
238000001704 evaporation Methods 0.000 description 2
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238000002474 experimental method Methods 0.000 description 2
201000000079 gynecomastia Diseases 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229910052742 iron Inorganic materials 0.000 description 2
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239000012280 lithium aluminium hydride Substances 0.000 description 2
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 2
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229910052987 metal hydride Inorganic materials 0.000 description 2
150000004681 metal hydrides Chemical class 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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238000007911 parenteral administration Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
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AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
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208000023599 acquired hyperprolactinemia Diseases 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
125000005907 alkyl ester group Chemical group 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
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000003509 anti-fertility effect Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
230000008195 breast development Effects 0.000 description 1
208000011803 breast fibrocystic disease Diseases 0.000 description 1
YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
229910052793 cadmium Inorganic materials 0.000 description 1
BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
SAHHMCVYMGARBT-HEESEWQSSA-N chanoclavine-I Chemical compound C1=CC([C@H]([C@H](NC)C2)\C=C(/C)CO)=C3C2=CNC3=C1 SAHHMCVYMGARBT-HEESEWQSSA-N 0.000 description 1
ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
229960001076 chlorpromazine Drugs 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
230000002196 ecbolic effect Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
OWEUDBYTKOYTAD-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=C2C3=CC=CC4=NC=C([C]34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 OWEUDBYTKOYTAD-MKTPKCENSA-N 0.000 description 1
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 1
229960001405 ergometrine Drugs 0.000 description 1
NESVMZOPWPCFAU-ZPRCMDFASA-N ergosine 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)C2)=C3C2=CNC3=C1 NESVMZOPWPCFAU-ZPRCMDFASA-N 0.000 description 1
230000001076 estrogenic effect Effects 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000002622 gonadotropin Substances 0.000 description 1
229940094892 gonadotropins Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000000380 hallucinogen Substances 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
208000031424 hyperprolactinemia Diseases 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
229930005303 indole alkaloid Natural products 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
150000002475 indoles Chemical class 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
BIXJFIJYBLJTMK-MEBBXXQBSA-N lysergol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=CNC3=C1 BIXJFIJYBLJTMK-MEBBXXQBSA-N 0.000 description 1
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical class [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
229940028370 methergine Drugs 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
RNHDWLRHUJZABX-IAQYHMDHSA-N methyl (6ar,9r)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)OC)C2)=C3C2=CNC3=C1 RNHDWLRHUJZABX-IAQYHMDHSA-N 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000011368 organic material Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000033116 oxidation-reduction process Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
125000000075 primary alcohol group Chemical group 0.000 description 1
239000000047 product Substances 0.000 description 1
201000002140 prolactin producing pituitary tumor Diseases 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
229940001470 psychoactive drug Drugs 0.000 description 1
239000004089 psychotropic agent Substances 0.000 description 1
238000011160 research Methods 0.000 description 1
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
229910001958 silver carbonate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
239000012085 test solution Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
239000011135 tin Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid 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 in position 8
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/10—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hetero atoms directly attached in position 8

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA228,474A 1974-08-02 1975-06-04 Synthese de l'elymoclavine et de ses derives Expired CA1051879A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US494149A US3923812A (en)	1974-08-02	1974-08-02	Synthesis of elymoclavine
US494147A US3929796A (en)	1974-08-02	1974-08-02	Synthesis of penniclavine and elymoclavine

Publications (1)

Publication Number	Publication Date
CA1051879A true CA1051879A (fr)	1979-04-03

Family

ID=27051314

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA228,474A Expired CA1051879A (fr)	1974-08-02	1975-06-04	Synthese de l'elymoclavine et de ses derives
CA228,512A Expired CA1042423A (fr)	1974-08-02	1975-06-04	Synthese de la penniclavine et de ses derives

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA228,512A Expired CA1042423A (fr)	1974-08-02	1975-06-04	Synthese de la penniclavine et de ses derives

Country Status (8)

Country	Link
CA (2)	CA1051879A (fr)
CH (5)	CH612966A5 (fr)
DE (1)	DE2534512A1 (fr)
FR (1)	FR2284327A1 (fr)
GB (2)	GB1521312A (fr)
IE (1)	IE41475B1 (fr)
IL (2)	IL47485A (fr)
NL (2)	NL7508938A (fr)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL7102982A (fr) *	1970-03-20	1971-09-22	Farmaceutici Italia

1975
- 1975-06-04 CA CA228,474A patent/CA1051879A/fr not_active Expired
- 1975-06-04 CA CA228,512A patent/CA1042423A/fr not_active Expired
- 1975-06-09 IE IE1293/75A patent/IE41475B1/en unknown
- 1975-06-16 IL IL47485A patent/IL47485A/xx unknown
- 1975-07-18 CH CH946975A patent/CH612966A5/xx not_active IP Right Cessation
- 1975-07-18 CH CH947075A patent/CH613967A5/xx not_active IP Right Cessation
- 1975-07-18 CH CH121079A patent/CH614206A5/xx not_active IP Right Cessation
- 1975-07-18 CH CH120979A patent/CH613704A5/xx not_active IP Right Cessation
- 1975-07-18 CH CH187679A patent/CH613703A5/xx not_active IP Right Cessation
- 1975-07-25 NL NL7508938A patent/NL7508938A/xx not_active Application Discontinuation
- 1975-07-25 NL NL7508939A patent/NL7508939A/xx not_active Application Discontinuation
- 1975-07-29 GB GB7408/78A patent/GB1521312A/en not_active Expired
- 1975-07-29 GB GB31643/75A patent/GB1521311A/en not_active Expired
- 1975-08-01 FR FR7524133A patent/FR2284327A1/fr active Granted
- 1975-08-01 DE DE19752534512 patent/DE2534512A1/de not_active Ceased
1977
- 1977-10-25 IL IL53215A patent/IL53215A0/xx unknown

Also Published As

Publication number	Publication date
IL47485A0 (en)	1976-03-31
DE2534512A1 (de)	1976-02-12
CH613703A5 (en)	1979-10-15
CH613967A5 (en)	1979-10-31
CH614206A5 (en)	1979-11-15
IE41475L (en)	1976-02-02
FR2284327B1 (fr)	1978-11-10
IE41475B1 (en)	1980-01-16
FR2284327A1 (fr)	1976-04-09
CA1042423A (fr)	1978-11-14
CH613704A5 (en)	1979-10-15
NL7508939A (nl)	1976-02-04
IL53215A0 (en)	1977-12-30
IL47485A (en)	1978-10-31
CH612966A5 (en)	1979-08-31
GB1521311A (en)	1978-08-16
GB1521312A (en)	1978-08-16
NL7508938A (nl)	1976-02-04

Publication	Publication Date	Title
US3901894A (en)	1975-08-26	8-thiomethylergolines
US3920664A (en)	1975-11-18	D-2-halo-6-alkyl-8-substituted ergolines and related compounds
US4054660A (en)	1977-10-18	Method of inhibiting prolactin
EP0026671B1 (fr)	1984-12-05	Dérivés d'ergoline, compositions les contenant, leur préparation et leur utilisation comme médicaments
US4031097A (en)	1977-06-21	Descarboxylysergic acid
US4075212A (en)	1978-02-21	Method of preparing 8,8-disubstituted-6-methylergolines and related compounds
CA1051879A (fr)	1979-04-03	Synthese de l'elymoclavine et de ses derives
US4001242A (en)	1977-01-04	D-6-methyl-8-formyl-10α-alkoxy-8-ergolene
IL42730A (en)	1976-06-30	D-6-methyl-2,8-disubstituted ergolines,their preparation and pharmaceutical compositions containing them
US3968112A (en)	1976-07-06	Synthesis of penniclavine and elymoclavine
CA1142176B (fr)	1983-03-01	2-azaergolines et 2-aza-8 (ou 9)-ergolenes
US3923812A (en)	1975-12-02	Synthesis of elymoclavine
US4609731A (en)	1986-09-02	Process for brominating ergot alkaloids
USRE30219E (en)	1980-02-19	Method of preparing 8,8-disubstituted-6-methylergolines and related compounds
US4082753A (en)	1978-04-04	Penniclavine acetonide
US4054567A (en)	1977-10-18	6-Methyl-8β-hydroxymethyl-8-γ-substituted-9-ergolene compounds
US4098790A (en)	1978-07-04	Ergoline chlorination process
US3880856A (en)	1975-04-29	Ergoline dimers
US3954772A (en)	1976-05-04	Descarboxylysergic acid
US3929796A (en)	1975-12-30	Synthesis of penniclavine and elymoclavine
USRE30218E (en)	1980-02-19	8,8-Disubstituted-6-methylergolines and related compounds
KR950008970B1 (ko)	1995-08-10	t-부틸 에르골린 유도체의 제조방법
US4075213A (en)	1978-02-21	8-Aryl-9-ergolenes
NO774133L (no)	1978-06-07	Ergolinderivater og fremgangsmaate til fremstilling derav
KR790001074B1 (ko)	1979-08-24	8,8-이치환-6-메틸에르골린류의 제조방법