CS231591A3 - Process for preparing 6-acyl, 7-acyl and 6,7-diacyl analogs of forskolin and their intermediates - Google Patents

Process for preparing 6-acyl, 7-acyl and 6,7-diacyl analogs of forskolin and their intermediates Download PDF

Info

Publication number: CS231591A3
Authority: CS; Czechoslovakia
Prior art keywords: alkyl; hydrogen; compound; acyl; compounds
Prior art date: 1990-07-24

Application number

CS912315A

Other languages

Czech (cs)

English (en)

Inventor

Souza Noel John Dr De

Premanand Durgarao Dr Desai

Shrikant Vishwanath Savanur

Jurgen Dr Blumbach

Original Assignee

Hoechst Ag

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.)

1990-07-24

Filing date

1991-07-23

Publication date

1992-02-19

1991-07-23 Application filed by Hoechst Ag filed Critical Hoechst Ag

1992-02-19 Publication of CS231591A3 publication Critical patent/CS231591A3/cs

Links

OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 title claims description 13
SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 title claims description 7
OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 title claims description 7
239000000543 intermediate Substances 0.000 title description 3
238000004519 manufacturing process Methods 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 80
-1 -37-aryl Chemical group 0.000 claims description 26
238000000034 method Methods 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
150000002367 halogens Chemical group 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical group 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
125000000547 substituted alkyl group Chemical group 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
229910052799 carbon Inorganic materials 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
239000011593 sulfur Substances 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
125000002348 vinylic group Chemical group 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
239000000243 solution Substances 0.000 description 18
229920002554 vinyl polymer Polymers 0.000 description 18
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 14
239000000047 product Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
239000000203 mixture Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
230000010933 acylation Effects 0.000 description 5
238000005917 acylation reaction Methods 0.000 description 5
239000012267 brine Substances 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011734 sodium Substances 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
238000003756 stirring Methods 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
241001510512 Chlamydia phage 2 Species 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000012445 acidic reagent Substances 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
239000003708 ampul Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000009835 boiling Methods 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
241001107954 Jola Species 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000002585 base Substances 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
230000020176 deacylation Effects 0.000 description 1
238000005947 deacylation reaction Methods 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005252 haloacyl group Chemical group 0.000 description 1
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 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
239000000155 melt Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

CS912315A 1990-07-24 1991-07-23 Process for preparing 6-acyl, 7-acyl and 6,7-diacyl analogs of forskolin and their intermediates CS231591A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP90114126		1990-07-24

Publications (1)

Publication Number	Publication Date
CS231591A3 true CS231591A3 (en)	1992-02-19

Family

ID=8204251

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS912315A CS231591A3 (en)	1990-07-24	1991-07-23	Process for preparing 6-acyl, 7-acyl and 6,7-diacyl analogs of forskolin and their intermediates

Country Status (15)

Country	Link
EP (1)	EP0468444A1 (ja)
JP (1)	JPH04234380A (ja)
KR (1)	KR920002575A (ja)
CN (1)	CN1058402A (ja)
AU (1)	AU8121091A (ja)
CA (1)	CA2047616A1 (ja)
CS (1)	CS231591A3 (ja)
FI (1)	FI913508A7 (ja)
HU (1)	HU208968B (ja)
IE (1)	IE912594A1 (ja)
IL (1)	IL98916A0 (ja)
MX (1)	MX9100343A (ja)
PL (1)	PL291198A1 (ja)
YU (1)	YU128191A (ja)
ZA (1)	ZA915761B (ja)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0482885A (ja) *	1990-07-23	1992-03-16	Nippon Kayaku Co Ltd	６―アシル―７―デアセチルフォルスコリン誘導体の新規な製造法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2614891B1 (fr) *	1987-05-04	1991-05-24	Roussel Uclaf	Nouveaux derives de la forskoline, leur procede de preparation, leur application comme medicaments, les compositions pharmaceutiques les renfermant ainsi que des intermediaires de leur procede de preparation

1991
- 1991-07-22 KR KR1019910012502A patent/KR920002575A/ko not_active Withdrawn
- 1991-07-22 FI FI913508A patent/FI913508A7/fi unknown
- 1991-07-22 YU YU128191A patent/YU128191A/sh unknown
- 1991-07-22 IL IL98916A patent/IL98916A0/xx unknown
- 1991-07-23 JP JP3182433A patent/JPH04234380A/ja active Pending
- 1991-07-23 EP EP91112325A patent/EP0468444A1/en not_active Withdrawn
- 1991-07-23 AU AU81210/91A patent/AU8121091A/en not_active Abandoned
- 1991-07-23 ZA ZA915761A patent/ZA915761B/xx unknown
- 1991-07-23 PL PL29119891A patent/PL291198A1/xx unknown
- 1991-07-23 CA CA002047616A patent/CA2047616A1/en not_active Abandoned
- 1991-07-23 CS CS912315A patent/CS231591A3/cs unknown
- 1991-07-23 CN CN91105003A patent/CN1058402A/zh active Pending
- 1991-07-23 MX MX9100343A patent/MX9100343A/es unknown
- 1991-07-23 IE IE259491A patent/IE912594A1/en unknown
- 1991-07-24 HU HU912491A patent/HU208968B/hu not_active IP Right Cessation

Also Published As

Publication number	Publication date
YU128191A (sh)	1994-09-09
PL291198A1 (en)	1992-03-09
EP0468444A1 (en)	1992-01-29
ZA915761B (en)	1992-04-29
FI913508A0 (fi)	1991-07-22
FI913508A7 (fi)	1992-01-25
HU208968B (en)	1994-02-28
MX9100343A (es)	1992-02-28
HUT59122A (en)	1992-04-28
IL98916A0 (en)	1992-07-15
KR920002575A (ko)	1992-02-28
JPH04234380A (ja)	1992-08-24
HU912491D0 (en)	1991-12-30
IE912594A1 (en)	1992-01-29
AU8121091A (en)	1992-01-30
CN1058402A (zh)	1992-02-05
CA2047616A1 (en)	1992-01-25

Publication	Publication Date	Title
HUT58310A (en)	1992-02-28	Anti-atherosclerotic and anti-thrombotic 1-benzopyran-4-one- and 2-amino-1,3-benzoxazin-4-one derivatives, process for producing them and pharmaceutical compositions containing them
CA2196065A1 (en)	1996-02-08	2-phenyl indoles as anti-oestrogen drugs
JPH0676403B2 (ja)	1994-09-28	新規なベンゾ［５，６シクロヘプタ［１，２−ｂピリジン誘導体及びこれを含有する抗アレルギー剤
EP0076075A1 (en)	1983-04-06	Pharmaceutically active benzopyran compounds
EP0222413A2 (en)	1987-05-20	Novel forskolin derivatives
JP2983231B2 (ja)	1999-11-29	インドロカルバゾル誘導体、その調製方法および薬剤としての使用
US5438050A (en)	1995-08-01	Indolocarbazole derivatives, processes for their preparation and compositions containing them
HU182084B (en)	1983-12-28	Process for preparing new piperidino-propoxy-quinolines and -coumarins
JP3009465B2 (ja)	2000-02-14	６，９−ビス（置換アミノ）ベンゾ〔ｇ〕イソキノリン−５，１０−ジオン類
US5221681A (en)	1993-06-22	Substituted benzoxazepines and benzothiazepines
HU202853B (en)	1991-04-29	Process for producing 3-aminodihydrobenzo(b)pyran and benzothiopyran derivatives and pharmaceutical compositions comprising same as active ingredient
EP0311378B1 (en)	1994-04-27	6-Substituted alkoxy-2-oxo-1, 2-dihydroquinoxaline derivatives
JPH0227358B2 (ja)	1990-06-15
Inoue et al.	1994	Total synthesis of (±)-surugatoxin
JP3043802B2 (ja)	2000-05-22	エトポシド同族体類
CS231591A3 (en)	1992-02-19	Process for preparing 6-acyl, 7-acyl and 6,7-diacyl analogs of forskolin and their intermediates
HUT71132A (en)	1995-11-28	Bis-aryl-carbinol derivatives, pharmaceutical compositions containing them and process for producing
White et al.	1970	Stereospecific synthesis of dl-cyclopenin and dl-cyclopenol
US5091388A (en)	1992-02-25	Pyridobenzoindole derivatives, their preparation and compositions which contain them
US4609733A (en)	1986-09-02	3-keto-substituted-N-pyridylindoles
PT96656A (pt)	1991-10-31	Processo de preparacao de derivados do pirazol e de composicoes farmaceuticas que os contem
EP0755928B1 (en)	2002-04-10	5-aminoflavone derivatives
HU208966B (en)	1994-02-28	Process for producing 6-(substituted amino-propionyl)-forskoline derivatives
FI76803C (fi)	1988-12-12	Foerarande foer framstaellning av 2-(4,5-dihydro-1h-imidazol-2-yl-1,2,4,5-tetrahydropyrrolo/3,2,1-hi/ indoler vilka har aktivitet mot 2-adrenergiska receptorer.
NO784094L (no)	1979-06-15	3-di-n-propyl-acetoxy-benzodiazepin-2-oner og fremgangsmaate til deres fremstilling