PT85581B - Processo para a preparacao de n-(s-3-alquilheptanoil)-d-gama-glutamil-glicil-d-alanina - Google Patents

Processo para a preparacao de n-(s-3-alquilheptanoil)-d-gama-glutamil-glicil-d-alanina Download PDF

Info

Publication number: PT85581B
Authority: PT; Portugal
Prior art keywords: acid; methyl; trans; hydroxy; ethyl
Prior art date: 1986-08-27

Application number

PT85581A

Other languages

English (en)

Portuguese (pt)

Other versions

PT85581A (en

Inventor

Charles W Murtiashaw

Original Assignee

Pfizer

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.)

1986-08-27

Filing date

1987-08-25

Publication date

1990-05-31

1986-08-27 Priority claimed from PCT/US1986/001772 external-priority patent/WO1988001612A1/en

1986-08-27 Priority claimed from PCT/US1986/001775 external-priority patent/WO1988001613A1/en

1987-08-25 Application filed by Pfizer filed Critical Pfizer

1987-09-01 Publication of PT85581A publication Critical patent/PT85581A/pt

1990-05-31 Publication of PT85581B publication Critical patent/PT85581B/pt

Links

238000000034 method Methods 0.000 title claims description 88
238000002360 preparation method Methods 0.000 title claims description 40
230000008569 process Effects 0.000 title claims description 27
239000002253 acid Substances 0.000 claims description 48
150000001875 compounds Chemical class 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 36
-1 trans-R-4-hepten-2-ol Chemical compound 0.000 claims description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 29
239000002904 solvent Substances 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
239000003153 chemical reaction reagent Substances 0.000 claims description 20
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
150000002148 esters Chemical class 0.000 claims description 18
230000007062 hydrolysis Effects 0.000 claims description 15
238000006460 hydrolysis reaction Methods 0.000 claims description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
229910052500 inorganic mineral Inorganic materials 0.000 claims description 14
239000011707 mineral Substances 0.000 claims description 14
238000005984 hydrogenation reaction Methods 0.000 claims description 13
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 9
150000002431 hydrogen Chemical class 0.000 claims description 9
VOGZQUBNQCQGNN-WEWAHIQMSA-N (e,3r)-hept-4-en-3-ol Chemical compound CC\C=C\[C@H](O)CC VOGZQUBNQCQGNN-WEWAHIQMSA-N 0.000 claims description 8
KWUXUOPPQQMMIL-MXTDHUQFSA-N (e,3r)-hex-4-en-3-ol Chemical compound CC[C@@H](O)\C=C\C KWUXUOPPQQMMIL-MXTDHUQFSA-N 0.000 claims description 8
239000012442 inert solvent Substances 0.000 claims description 8
KWUXUOPPQQMMIL-HWKANZROSA-N (e)-hex-4-en-3-ol Chemical compound CCC(O)\C=C\C KWUXUOPPQQMMIL-HWKANZROSA-N 0.000 claims description 7
239000003960 organic solvent Substances 0.000 claims description 7
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 7
RFYQVSFBWCSKGJ-QMMMGPOBSA-N (3r)-3-ethylhept-4-enoic acid Chemical compound CCC=C[C@H](CC)CC(O)=O RFYQVSFBWCSKGJ-QMMMGPOBSA-N 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 6
XRWMJTDFZGUSLR-ZETCQYMHSA-N (3r)-3-methylhept-4-enoic acid Chemical compound CCC=C[C@H](C)CC(O)=O XRWMJTDFZGUSLR-ZETCQYMHSA-N 0.000 claims description 5
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 5
VOGZQUBNQCQGNN-AATRIKPKSA-N (e)-hept-4-en-3-ol Chemical compound CC\C=C\C(O)CC VOGZQUBNQCQGNN-AATRIKPKSA-N 0.000 claims description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 4
230000005494 condensation Effects 0.000 claims description 4
238000002425 crystallisation Methods 0.000 claims description 4
230000008025 crystallization Effects 0.000 claims description 4
238000010438 heat treatment Methods 0.000 claims description 4
230000001590 oxidative effect Effects 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
239000010936 titanium Substances 0.000 claims description 4
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 3
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 3
229910052719 titanium Inorganic materials 0.000 claims description 3
238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
230000009467 reduction Effects 0.000 claims description 2
125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 10
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims 6
RFYQVSFBWCSKGJ-GJIOHYHPSA-N (e,3r)-3-ethylhept-4-enoic acid Chemical compound CC\C=C\[C@H](CC)CC(O)=O RFYQVSFBWCSKGJ-GJIOHYHPSA-N 0.000 claims 2
NRBOLXCMYWKXSS-UHFFFAOYSA-N 4-methylhexane-1,1-diol Chemical compound CCC(C)CCC(O)O NRBOLXCMYWKXSS-UHFFFAOYSA-N 0.000 claims 2
125000004185 ester group Chemical group 0.000 claims 2
QVTWBMUAJHVAIJ-UHFFFAOYSA-N hexane-1,4-diol Chemical compound CCC(O)CCCO QVTWBMUAJHVAIJ-UHFFFAOYSA-N 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
WZHKDGJSXCTSCK-FNORWQNLSA-N (E)-Hept-3-ene Chemical compound CCC\C=C\CC WZHKDGJSXCTSCK-FNORWQNLSA-N 0.000 claims 1
KFXPOIKSDYRVKS-UHFFFAOYSA-N (Z)-4-Heptenoic acid Natural products CCC=CCCC(O)=O KFXPOIKSDYRVKS-UHFFFAOYSA-N 0.000 claims 1
XRWMJTDFZGUSLR-KPJROHGDSA-N (e,3r)-3-methylhept-4-enoic acid Chemical compound CC\C=C\[C@H](C)CC(O)=O XRWMJTDFZGUSLR-KPJROHGDSA-N 0.000 claims 1
FLYIRERUSAMCDQ-UHFFFAOYSA-N 2-azaniumyl-2-(2-methylphenyl)acetate Chemical compound CC1=CC=CC=C1C(N)C(O)=O FLYIRERUSAMCDQ-UHFFFAOYSA-N 0.000 claims 1
KFXPOIKSDYRVKS-ONEGZZNKSA-N 4-Heptenoic acid Chemical compound CC\C=C\CCC(O)=O KFXPOIKSDYRVKS-ONEGZZNKSA-N 0.000 claims 1
ONKMSEGLLBBJKF-UHFFFAOYSA-N 5-methylhept-1-en-1-ol Chemical compound OC=CCCC(CC)C ONKMSEGLLBBJKF-UHFFFAOYSA-N 0.000 claims 1
CUKAXHVLXKIPKF-UHFFFAOYSA-N hept-4-en-1-ol Chemical compound CCC=CCCCO CUKAXHVLXKIPKF-UHFFFAOYSA-N 0.000 claims 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 1
CEOCUCXOSQUXGV-UHFFFAOYSA-N methanidylphosphanium Chemical compound [PH3]=C CEOCUCXOSQUXGV-UHFFFAOYSA-N 0.000 claims 1
230000008707 rearrangement Effects 0.000 claims 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
229920002554 vinyl polymer Polymers 0.000 claims 1
239000000047 product Substances 0.000 description 118
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
239000000203 mixture Substances 0.000 description 43
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
239000000243 solution Substances 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
239000003921 oil Substances 0.000 description 19
239000012044 organic layer Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000706 filtrate Substances 0.000 description 18
150000001299 aldehydes Chemical class 0.000 description 16
239000003054 catalyst Substances 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
239000000543 intermediate Substances 0.000 description 15
239000010410 layer Substances 0.000 description 15
238000003756 stirring Methods 0.000 description 15
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
238000001914 filtration Methods 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
239000007787 solid Substances 0.000 description 11
238000005160 1H NMR spectroscopy Methods 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
239000000284 extract Substances 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000004957 immunoregulator effect Effects 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 7
239000003480 eluent Substances 0.000 description 7
238000005507 spraying Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
239000003810 Jones reagent Substances 0.000 description 6
239000005909 Kieselgur Substances 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
238000004821 distillation Methods 0.000 description 6
125000004356 hydroxy functional group Chemical group O* 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000007858 starting material Substances 0.000 description 6
238000005406 washing Methods 0.000 description 6
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 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
238000006809 Jones oxidation reaction Methods 0.000 description 5
238000009835 boiling Methods 0.000 description 5
239000007789 gas Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
238000011282 treatment Methods 0.000 description 4
230000008016 vaporization Effects 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 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
239000003377 acid catalyst Substances 0.000 description 3
150000001336 alkenes Chemical class 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
238000011109 contamination Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
238000002955 isolation Methods 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000002524 organometallic group Chemical group 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
102000004196 processed proteins & peptides Human genes 0.000 description 3
238000012545 processing Methods 0.000 description 3
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000009834 vaporization Methods 0.000 description 3
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 3
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 2
ZXABMDQSAABDMG-UHFFFAOYSA-N 3-ethenoxyprop-1-ene Chemical compound C=CCOC=C ZXABMDQSAABDMG-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000009471 action Effects 0.000 description 2
239000008272 agar Substances 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
230000001010 compromised effect Effects 0.000 description 2
MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 2
MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000006735 epoxidation reaction Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000003022 immunostimulating agent Substances 0.000 description 2
230000003308 immunostimulating effect Effects 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
239000007788 liquid Substances 0.000 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000002243 precursor Substances 0.000 description 2
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
238000011084 recovery Methods 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000008107 starch Substances 0.000 description 2
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
ILYVXUGGBVATGA-HSHFZTNMSA-N (2r)-2-aminopropanoic acid;hydrochloride Chemical compound Cl.C[C@@H](N)C(O)=O ILYVXUGGBVATGA-HSHFZTNMSA-N 0.000 description 1
RNZKYQHTFUFVSS-ZLUZDFLPSA-N (2r,6r)-2-amino-6-[[4-carboxy-4-[[(2s)-2-[[(2r)-2-hydroxypropanoyl]amino]propanoyl]amino]butanoyl]amino]-7-(carboxymethylamino)-7-oxoheptanoic acid Chemical compound C[C@@H](O)C(=O)N[C@@H](C)C(=O)NC(C(O)=O)CCC(=O)N[C@@H](C(=O)NCC(O)=O)CCC[C@@H](N)C(O)=O RNZKYQHTFUFVSS-ZLUZDFLPSA-N 0.000 description 1
YOTCOXJRZMRFKJ-QMMMGPOBSA-N (3r)-3-ethylhept-4-enoyl chloride Chemical compound CCC=C[C@H](CC)CC(Cl)=O YOTCOXJRZMRFKJ-QMMMGPOBSA-N 0.000 description 1
BTSIZIIPFNVMHF-ONEGZZNKSA-N (E)-2-penten-1-ol Chemical compound CC\C=C\CO BTSIZIIPFNVMHF-ONEGZZNKSA-N 0.000 description 1
DTCCTIQRPGSLPT-ONEGZZNKSA-N (E)-2-pentenal Chemical compound CC\C=C\C=O DTCCTIQRPGSLPT-ONEGZZNKSA-N 0.000 description 1
JHEPBQHNVNUAFL-AATRIKPKSA-N (e)-hex-1-en-1-ol Chemical compound CCCC\C=C\O JHEPBQHNVNUAFL-AATRIKPKSA-N 0.000 description 1
PGPXSPCSXBRFNI-FCZSHJHJSA-N (e,5r)-5-ethenoxyhept-3-ene Chemical compound CC\C=C\[C@@H](CC)OC=C PGPXSPCSXBRFNI-FCZSHJHJSA-N 0.000 description 1
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
LTDYEDCDJFHPFI-HSHFZTNMSA-N 2-aminoacetic acid;(2r)-2-aminopropanoic acid Chemical compound NCC(O)=O.C[C@@H](N)C(O)=O LTDYEDCDJFHPFI-HSHFZTNMSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
DVESMWJFKVAFSP-UHFFFAOYSA-N 3-Methyl-heptanoic acid Chemical compound CCCCC(C)CC(O)=O DVESMWJFKVAFSP-UHFFFAOYSA-N 0.000 description 1
YOTCOXJRZMRFKJ-UHFFFAOYSA-N 3-ethylhept-4-enoyl chloride Chemical compound CCC=CC(CC)CC(Cl)=O YOTCOXJRZMRFKJ-UHFFFAOYSA-N 0.000 description 1
108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
241000206761 Bacillariophyta Species 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
238000009631 Broth culture Methods 0.000 description 1
125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
238000005821 Claisen rearrangement reaction Methods 0.000 description 1
PXXNTAGJWPJAGM-VCOUNFBDSA-N Decaline Chemical compound C=1([C@@H]2C3)C=C(OC)C(OC)=CC=1OC(C=C1)=CC=C1CCC(=O)O[C@H]3C[C@H]1N2CCCC1 PXXNTAGJWPJAGM-VCOUNFBDSA-N 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
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241001331845 Equus asinus x caballus Species 0.000 description 1
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
206010062016 Immunosuppression Diseases 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
239000002841 Lewis acid Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
229910017917 NH4 Cl Inorganic materials 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
239000004677 Nylon Substances 0.000 description 1
BUIQRTDBPCHRIR-UHFFFAOYSA-L O[Cr](Cl)(=O)=O Chemical compound O[Cr](Cl)(=O)=O BUIQRTDBPCHRIR-UHFFFAOYSA-L 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108010013639 Peptidoglycan Proteins 0.000 description 1
244000137852 Petrea volubilis Species 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
241000700159 Rattus Species 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
240000006365 Vitis vinifera Species 0.000 description 1
235000014787 Vitis vinifera Nutrition 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
206010052428 Wound Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000002411 adverse Effects 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229920000180 alkyd Polymers 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000002924 anti-infective effect Effects 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
DTCCTIQRPGSLPT-UHFFFAOYSA-N beta-Aethyl-acrolein Natural products CCC=CC=O DTCCTIQRPGSLPT-UHFFFAOYSA-N 0.000 description 1
230000008512 biological response Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000007767 bonding agent Substances 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
244000309464 bull Species 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004927 clay Substances 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
230000029087 digestion Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
VOGZQUBNQCQGNN-UHFFFAOYSA-N hept-4-en-3-ol Chemical compound CCC=CC(O)CC VOGZQUBNQCQGNN-UHFFFAOYSA-N 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
230000002519 immonomodulatory effect Effects 0.000 description 1
229960001438 immunostimulant agent Drugs 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
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238000011065 in-situ storage Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
238000005259 measurement 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
GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
244000000010 microbial pathogen Species 0.000 description 1
244000005700 microbiome Species 0.000 description 1
HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 1
210000003739 neck Anatomy 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
BTSIZIIPFNVMHF-UHFFFAOYSA-N nor-leaf alcohol Natural products CCC=CCO BTSIZIIPFNVMHF-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
238000005949 ozonolysis reaction Methods 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
230000037361 pathway Effects 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
239000006187 pill Substances 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
238000011027 product recovery Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group 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
230000001105 regulatory effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000010583 slow cooling Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
210000005239 tubule Anatomy 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

PT85581A 1986-08-27 1987-08-25 Processo para a preparacao de n-(s-3-alquilheptanoil)-d-gama-glutamil-glicil-d-alanina PT85581B (pt)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
PCT/US1986/001772 WO1988001612A1 (en)	1986-08-27	1986-08-27	Processes and intermediates for n-(s-3-alkyl-heptanoyl)-d-gamma-glutamyl-glycyl-d-alanine
PCT/US1986/001775 WO1988001613A1 (en)	1986-08-27	1986-08-27	Crystalline n-(s-3-methylheptanoyl)-d-gamma-glutamyl-glycyl-d-alanine, and processes and intermediates therefor

Publications (2)

Publication Number	Publication Date
PT85581A PT85581A (en)	1987-09-01
PT85581B true PT85581B (pt)	1990-05-31

Family

ID=26773904

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PT85581A PT85581B (pt)	1986-08-27	1987-08-25	Processo para a preparacao de n-(s-3-alquilheptanoil)-d-gama-glutamil-glicil-d-alanina

Country Status (12)

Country	Link
JP (1)	JPH0637517B2 (da)
KR (1)	KR900004106B1 (da)
CN (1)	CN1021436C (da)
DK (1)	DK444887A (da)
EG (1)	EG18303A (da)
IL (1)	IL83657A (da)
MY (1)	MY101823A (da)
NZ (1)	NZ221570A (da)
PH (1)	PH27397A (da)
PL (1)	PL156175B1 (da)
PT (1)	PT85581B (da)
YU (1)	YU46663B (da)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN113548977A (zh) *	2021-07-12	2021-10-26	广州乐信生物科技有限公司	N-甲基-β-丙氨酸衍生物的制备方法

1987
- 1987-08-13 EG EG467/87A patent/EG18303A/xx active
- 1987-08-24 YU YU155987A patent/YU46663B/sh unknown
- 1987-08-25 MY MYPI87001442A patent/MY101823A/en unknown
- 1987-08-25 PT PT85581A patent/PT85581B/pt not_active IP Right Cessation
- 1987-08-25 PL PL1987267444A patent/PL156175B1/pl unknown
- 1987-08-26 NZ NZ221570A patent/NZ221570A/xx unknown
- 1987-08-26 IL IL83657A patent/IL83657A/xx not_active IP Right Cessation
- 1987-08-26 DK DK444887A patent/DK444887A/da not_active Application Discontinuation
- 1987-08-26 CN CN87105898A patent/CN1021436C/zh not_active Expired - Fee Related
- 1987-08-26 KR KR1019870009313A patent/KR900004106B1/ko not_active Expired
- 1987-08-27 JP JP62214128A patent/JPH0637517B2/ja not_active Expired - Lifetime
1989
- 1989-08-01 PH PH39031A patent/PH27397A/en unknown

Also Published As

Publication number	Publication date
YU46663B (sh)	1994-01-20
EG18303A (en)	1992-12-30
CN1021436C (zh)	1993-06-30
JPH0637517B2 (ja)	1994-05-18
MY101823A (en)	1992-01-31
DK444887A (da)	1988-02-28
PH27397A (en)	1993-06-21
NZ221570A (en)	1989-09-27
PL267444A1 (en)	1988-07-21
KR900004106B1 (ko)	1990-06-15
YU155987A (en)	1989-02-28
CN87105898A (zh)	1988-03-09
PT85581A (en)	1987-09-01
IL83657A (en)	1992-03-29
PL156175B1 (en)	1992-02-28
DK444887D0 (da)	1987-08-26
KR880002896A (ko)	1988-05-12
IL83657A0 (en)	1988-01-31
JPS6368598A (ja)	1988-03-28

Legal Events

Date

Code

Title

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1995-10-20

MM3A

Annulment or lapse

Free format text: LAPSE DUE TO NON-PAYMENT OF FEES

Effective date: 19950531

Publication	Publication Date	Title
Heffner et al.	1992	Total synthesis of (-)-nummularine F
EP0051391B1 (en)	1984-09-05	Bicyclic compounds, their production and use
FI78684B (fi)	1989-05-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara cis, endo-2-azabicyklo-/5.3.0/-dekan-3- karboxylsyraderivat och mellanprodukter.
JPS5849350A (ja)	1983-03-23	免疫調節に影響を与えるペプチド
WO1994019334A1 (fr)	1994-09-01	Derive du pf 1022 utilise comme depsipeptide cyclqiue
NZ199310A (en)	1985-10-11	Peptides and peptide derivatives containing 3-5 amino acid residues;compositions
US4362716A (en)	1982-12-07	Dipeptides, their preparation and compositions containing them
PT85581B (pt)	1990-05-31	Processo para a preparacao de n-(s-3-alquilheptanoil)-d-gama-glutamil-glicil-d-alanina
CA1170599A (en)	1984-07-10	N-acyl peptide compound, process for the preparation thereof and the pharmaceutical compositions
DK154434B (da)	1988-11-14	Analogifremgangsmaade til fremstilling af tripeptidderivater
JPH0647599B2 (ja)	1994-06-22	ヘプタノイル―Ｇｌｕ―Ａｓｐ―Ａｌａ―アミノ酸系免疫賦活薬
EP0006068A2 (fr)	1979-12-12	Composés du type muramyl-peptide et médicaments les contenant
US5371187A (en)	1994-12-06	Crystalline N-(S-3-methylheptanoyl)-D-gamma-glutamyl-glycyl-D-alanine, and processes and intermediates therefor
US5245079A (en)	1993-09-14	Processes and intermediates for N-(S-3-alkyl-heptanoyl)-D-gamma-glutamyl-glycyl-D-alanine
EP0258032B1 (en)	1992-07-29	Processes and intermediates for n-(s-3-alkylheptanoyl)-d-gamma-glutamyl-glycyl-d-alanine
JPH05148277A (ja)	1993-06-15	アミノホスホン酸誘導体
EP0259084B1 (en)	1992-07-22	Crystalline n-(s-3-methylheptanoyl)-d-gamma-glutamyl-glycyl-d-alanine, and processes and intermediates therefor
FI83523B (fi)	1991-04-15	Foerfarande foer framstaellning av terapeutiskt anvaendbara derivat av bicykliska aminosyror.
US5136020A (en)	1992-08-04	Crystalline n-(s-3-methylheptanoyl)-D-gamma-glutamyl-glycyl-D-alanine, and processes and intermediates therefor
US5134225A (en)	1992-07-28	Processes and intermediates for N-(S-3-alkyl-heptanoyl)-D-gamma-glutamyl-D-alanine
US5185464A (en)	1993-02-09	Crystalline N-(S-3-methylheptanoyl)-D-gamma-glutamyl-glycyl-D-alanine, and processes and intermediates therefor
JPS6230748A (ja)	1987-02-09	置換アミンのｌ−アミノカルボン酸アミド
CN88101653A (zh)	1988-10-26	高甜度的l-天冬氨酰基-3-(二环烷基)-l-丙氨酸烷基酯
Kishore et al.	1984	Synthesis and conformations of stereochemically restricted analogs of Leu 5-enkephalinamide. Substitution of α-aminoisobutyric acid and 1-aminocyclopentane-1-carboxylic acid at positions 2 and 3
KR830002059B1 (ko)	1983-10-08	멀아밀-펲타이드형태인 신규 화합물의 제조방법