CS196526B1 - Process for preparing derivatives of saccharides with antitumor effect - Google Patents
Process for preparing derivatives of saccharides with antitumor effect Download PDFInfo
- Publication number
- CS196526B1 CS196526B1 CS254274A CS254274A CS196526B1 CS 196526 B1 CS196526 B1 CS 196526B1 CS 254274 A CS254274 A CS 254274A CS 254274 A CS254274 A CS 254274A CS 196526 B1 CS196526 B1 CS 196526B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- hydrazone
- acetyl
- pentulose
- erythro
- dichlorophenyl
- Prior art date
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- 230000000259 anti-tumor effect Effects 0.000 title claims description 5
- 150000001720 carbohydrates Chemical class 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- 150000007857 hydrazones Chemical class 0.000 claims description 18
- -1 saccharide hydrazone Chemical class 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000001719 carbohydrate derivatives Chemical class 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 3
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- BDXWAFMRWODOMC-JTQLQIEISA-N (2R)-3-[(2-nitrophenyl)hydrazinylidene]butane-1,2,4-triol Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)NN=C(CO)[C@@H](O)CO BDXWAFMRWODOMC-JTQLQIEISA-N 0.000 description 1
- WXYXERHRDKEISL-ZXZARUISSA-N (2R,4S)-1,2,4,5-tetrahydroxypentan-3-one Chemical compound OC[C@H](O)C(=O)[C@H](O)CO WXYXERHRDKEISL-ZXZARUISSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 241000755710 Eilica Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
POPIS VYNÁLEZU
REPUBLIKA
<19> K AUTORSKÉMU OSVEDČENIU
(«> (23) Výstavná priorita(22) Přihlášené 09 04 74(21) PV 2542-74 196 526 (Π) ztaix (51) Int. d C 07 H 3/02
ÚftAD PRO VYNÁLEZYA OBJEVY (40) Zverejnené 31 07 7 9(45) Vydané Q1 4 82 (75) . ·
Autor vynálezu LÍNEK KAZIMÍR, ing., CSe., FUŠKA JÁN, ing., CSc., SANDTNEROVÁ RCZÁLIA, prom. chem. a KOVÁČIK VLADIMÍR, ing., CSc., BRATISLAVA' (54) Příprava derivátov sacharidov β protinédorovými účinkami 1
Vynález sa týká spůsobu přípravy niektorých acetylovaných hydrazónov sacharidov akopotenciálnych kanceroetatík.
Acetylované hydrazóny sacharidov majú protinédorové účinky /K, Linek, J. Fuška, R. Sandtnerovó, M. Kulhánek, A.O 163 115,/, hy*drazín sulfát sa začal používat ako kancero-statikum v humánněj terapii /Chemical and Engineerings News, October 29. 1973/.
Tento vynález sa týká přípravy nových derivátov sacharidov s protinádorovými účinka-mi a to tri-O-acetyl-D-treóza/2,5-dichlórfenyl/hydrazónu /1/, tri-O-acetyl-L-glycero--tetrulóza/2-nitrofenyl/hydrazónu /11/, tetra-0-acetyl-D-erytro-pentulóza/2-nitrofehyl//hydrazónu /111/ a tetra-0-acetyl-erytro-3-pentulóza/2,5-dichlórfenyl/hydrazónu, ktorá savyznačuje tým, že príaluáný hydrazón sacharidu sa acetyluje acetanhydridom za katalytické-ho účinku pyridinu pri teplote 0°C.
Potenciálně protinádorové účinky námi připravených látok I až IV sa hodnotili v po-kusoch in vitro na buňky EAC. Účinok látok sa hodnotil na základe inhibície inkorporácie prekurzorov syntézy nukleinových kyselin do buněčných frakcií EAC nerozpustných vladovej trichlóroctovej kyselina, metodou, ktorú popísali J.Fuška a spol. /Neoplasma,18/1971/631/. Všetky uvedené látky sú účinné a význačné inhibujú syntézu nukleinových kyse-lin/ Tabulka 1/, 196 526 198 328
Tabulka 1 Λ
Por. δ. Názov látky % inhibície inkorporácteprekurzorov do buniek EAC adenín /1/ Tri-0-acetyl-D-trěóza/2,5-dichlórdifenyl/h.ydrazón /11/ Tri-O-acetyl-L-glycero-tetrulóza /2-nitorfenyl/hydrazon /111/ Tetra-O-ucetyl-D-efcytro-pentulóza /2-nitrofenyl/hydrazón /IV/ Tetra-0-acetyl-erytro-3-pentulóza/2,5-dichlórfenyl/hydrazón Příklad 1' D-Treóza/2,5-dichlórfenyl/hydrazón /lg/ ea přidal do zmesi acetanhydridu /l,8ml/a pyridinu /3,6 ml/ ochladenej na C °C. Táto teplota reakčnej zmesi sa udržiavala počas2 hodin ža občasného mieáania^ reakčná zmeš potom stála v chladničke 16 hodin /3 °C/.
Reakčná zmes sa spracovala tým spBsobom, že acetanhydridu a pyridinu sa oddestilovala za vákua při 30 °C a přidal sa etanol /30 ml/, ktorý sa oddestiloval za tých istých podmie- nok. Vzniklý sirup sa dělil na štipci /60 x 3 cm/ silikagelu/Silikagel L; 40 - 100/ za použitia rozpúátadlovej sústavy benzén-octan etylnatý /9:1/. Čistota jednotlivých frakciísa kontrolovala tenkovrstvovou chromatograf ioti /Silikagel LS; 5-40/ za použitia tej istejrozpúšťadlovej sústavy a detekcia sa uskutočnilá postrekom platničiek 5 % kyselinou vetanole a zahrievanim. Získal sa chromatograficky čistý tri-0-ac,$tyl-D-treóza/2,5-dichlór-fenyl/hydrazón/1.06 g; 73,0 %/ vo formě sirupu f°$5- 33,2 °/c 0,5 , octan etylnatý/.Příklad 2 L-Glycero-tetrulóza /2-nitrofenyl/hydrazón /1 g/ sa acetyloval zmesou acetynhydrídu /2 ml/ a pyridinu /4 ml/ podobné ako v příklade 1; reakčná zmes sa spracovala tiež týmistým sp^sobom. Vzniklý sirup sa dělil na štipci silikagelu v rozpúšťadlovej sústavebenzén-octaň etylnatý /9:1/ podobné ako v příklade 1. Získal sa chromátograficky čistýtri-O-acetyl-L-glycertetrulóza/2-nitrofenyl/hydrazón /1,15 gj 76,9 %/ vo formě sirupuf45 -104 °/c 0,5, octan etylnatý/. Příklad 3 D-erytro-pentuloza /2-nitrofenyl/hydrazón /1 g/ sa acetyloval zmesou acetanhy- dridu /2,4 ml/ a pyridinu /4,8 ml/ a spracoval podobné ako v příklade 1. Vzniklý sirup sa dělil na štipci silikagelu v rozpúštJadlovej sústave benzén-octan etylnatý /7:3/. Získal sa chromatograficky čistý tetra-O-acetyl-Ď-erytro-pentulóza /2-nitrofenyl/hydrazón,
Claims (1)
196 S26 którý vykrystalizoval nad PgO^ vo vékuovom exsikétori /1,25 gi 78,6 %/. Po dyojnáaobnejkryštalizácii z etanolu látka mala b.t. 67 až 69 72 °/c 0,5, octan etylnatý/. Příklad 4 Erytro-3-pentulóza /2,5-dichlórfenyl/hydrazón /1 g/ ea acetyloval zmesou % acetanhydridu /2,3 ml/ a pyridinu /4,6 ml/ ako v příklade 1. Po oddeetilování acetylačnejzmesi sa přidal etanol, z ktorého vykraštalizoval příslušný acetylderivát/1,16 g; 75,1 %/.Po dvojnásobnéj kryštalizácii z etanolu málo látka b.t. 97 až 99 °C. PREDMET VYNÁLEZU Příprava derivátov sacharidov s protinádorovými účinkami, vyznačujúca ea tým, žepříslušný hydrazón sacharidu sa acetyluje acetanhydridom za katalytického účinku pyridinupri teplote O °C za vzniku trt-O-acetyl-D-treóza /2,5-dichlór-fenyl/hydrazónu, tri-O--acetyl-L-glycero.tetrulóza /2-nitrofenyl/hydrazónu, tetra-O-acetyl-D-erytro-pentulóza/2-nitrofenyl/hydrazónu a tetra-O-acetyl-erytro-3-pentulóza /2,5-dichlórfenyl/hydrazbnu. 1 &
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS254274A CS196526B1 (en) | 1974-04-09 | 1974-04-09 | Process for preparing derivatives of saccharides with antitumor effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS254274A CS196526B1 (en) | 1974-04-09 | 1974-04-09 | Process for preparing derivatives of saccharides with antitumor effect |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS196526B1 true CS196526B1 (en) | 1980-03-31 |
Family
ID=5362846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS254274A CS196526B1 (en) | 1974-04-09 | 1974-04-09 | Process for preparing derivatives of saccharides with antitumor effect |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS196526B1 (cs) |
-
1974
- 1974-04-09 CS CS254274A patent/CS196526B1/cs unknown
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