LV10943B - Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine - Google Patents
Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine Download PDFInfo
- Publication number
- LV10943B LV10943B LV940085A LV940085A LV10943B LV 10943 B LV10943 B LV 10943B LV 940085 A LV940085 A LV 940085A LV 940085 A LV940085 A LV 940085A LV 10943 B LV10943 B LV 10943B
- Authority
- LV
- Latvia
- Prior art keywords
- pyridine
- benzyloxycarbonyl
- arginine
- methylcoumarine
- hours
- Prior art date
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
LV 10943 Λ T, 3LITZIL0KSIKAP301TILA3GIĪTĪ1TA 4· ŽDA ILGŪŠA1TA3 I.Z3TOD2 7ILEULIAKIL-7-GB 10943 Λ T, 3LITZIL0KSIKAP301TILA3GGIETTA1 · · ODA LONG1TA3 I.Z3TOD2 7ILEULIAKIL-7-
Izgudrojums attiecas uz bioorganiskās ķīmijas nozari, galvenokārt uz fermentu substrātu iegūšanu, kuri tiek izmantot fermentu aktivitātes noteikšanai un to darbības mehānisma pētīšanai. U-Benziloksikarbonilarginīna 4-netilkunaril-7-smīds (Z-Arg-LIKA) (I) pieder pie fluorogēno fermentu substrātu j us klases, kuru darbība pamato "ermentativa 7-nmino-b—mc- tilkumarīna nošķelšanu un tā fluorescences spēju pie 440 nm.The invention relates to the field of bioorganic chemistry, mainly to the production of enzyme substrates, which are used to determine the activity of enzymes and to study their mechanism of action. U-Benzyloxycarbonylarginine 4-Nettylcuaryl-7-smid (Z-Arg-LIKA) (I) belongs to a class of fluorogenic enzyme substrates whose function justifies the cleavage of " ermentativa 7-nmino-b-mc-tilcumarin and its fluorescence at 440 nm.
Aprakstītas vairākas Z-Arg-I.TIA (ī) iejāšanas metodes.Several methods of entering Z-Arg-I.TIA (i) are described.
Literatūrā /1/ Z-Arg-IBL- (I) iejāts ar 1J /5-īgu iznākumu no Z-arginīna un 7-amino-4-metilkunarīna ar jaukto anhidrīcu metodi, pielietojot izobutilhlorforniātu.In the literature / 1 / Z-Arg-IBL- (I) was obtained with a 1J / 5-fold yield of Z-arginine and 7-amino-4-methylcunnarine by the mixed anhydrate method using isobutyl chloroformate.
Japāņu zinātnieku piedāvātajā metodē /2,3/ šo pašu savienojumu kondensēšanai tiek izmantots IT,II’-dicikloheksil-karbodiimīds un savienojuma I iznākums paaugstināts līdz 29 ,3-tiem.The method proposed by Japanese scientists / 2,3 / uses IT, II'-dicyclohexylcarbodiimide to condensate the same compounds and raises the yield of compound I to 29.3.
Ar 32 /—īgu iznākumu Z-Arg-I.IKŪ (I) iegūts literatūrā /4/, kurā izmantota modificēta fosfora pentoksīda metode.With 32% yield, Z-Arg-I.IKU (I) was obtained from literature / 4 / using a modified phosphorus pentoxide method.
Pozdņevs /5/ piedāvā vispārēju metodi II -aizvietota arginīna arilaiaīdu iegūšanai, kurā par kondensācijas aģentu izmantots di-treš-butiloirokarbonāts. Citu savienojumu starpā pieminēts arī Z-Arg-I.1IA (I), kam dots iznākums (73 / un kvalitātes rādītāji. bad ORIGINAL ģļ 2. LV 10943 -atad - visās literatūrā aprakstītajās metodes par -^6j^iGlarn tiek izmantoti Z—arginīna hidrogenhlorīcs, kas j-e£ūtG r.o Z-arginīra, un 7-amino-·t-metilkunarīns. Atšķiras kondensācijas metodes un produkta I iznākums. 'Visaugstākais Z-lrg-LIICA (I) iznākums (73 .3) uzrādīts literatūrā /5/, taču tajā nav dots sintēzes eksperimentālais apraksts, tāpēc par prototipu izvēlēta izgudrojuma metodei ķīmiski vistuvākā metode, kas piedāvāta literatūrā /4/: 7-Anino-4— metilkumarīna (17 g, 0,09 11) suspensiju diatilfosfītā (92 ml), kas satur trietilamīnu (12,5 ml, 0,09 īd) pre 110° c pievieno fosfora pentoksīda (25,5 g, 0,09 1-1) šķīdumam dietilfosfītā (92 ml). Pēc 20 minūtēm pie 90°C pievieno Z-arginīna hidrogenhlorīda (27,7 g, 0,09 Ll) šķīdumu dietilfosfītā (92 ml), kas satur 35 5 fosforskābi (10,4 g, 0,09 II). ilaisa 2 stundas 110°C temperatūrā. letvaicē (1 tors, vannas temperatūra 60°C). eļļainajam atlikumam pievieno 910 ml 1 II sālsskābes un maisa 90°C temperatūrā. Dzesējot progukts kristalizējas. Iztur 13 stundas 4°C temperatūrā, filtrē. Izšķīdina vārošā metanolā (2500 ml), atkrāso ar aktīvo ogli, filtrē un koncentrē, kamēr sāk kristalizēties. Iznākums 25,4 g (52 3). K.p. 213°C (sad.)io(jp0 - 17,0 (c=l; 11.11).Pozdnew / 5 / proposes a general method for the preparation of II-substituted arginine aryl aldehydes in which di-tert-butyl irocarbonate is used as a condensing agent. Among other compounds, mention is made of Z-Arg-I.1IA (I), which has yielded (73 / and quality indices. Bad ORIGINAL gl 2. EN 10943 -atad - all methods described in the literature for - ^ 6j ^ iGlarn are used in Z- arginine hydrochloride, which is a g -G ro Z-arginine, and 7-amino-t-methylcunararin, a different condensation method and product I. The highest yield of Z-lrg-LIICA (I) (73.3) is reported in the literature / 5 /, but does not provide an experimental description of the synthesis, the method chemically closest to the method of the invention proposed in the literature / 4 /: 7-Anino-4-methylcoumarin (17 g, 0.09 11) in diatyl phosphite (92 ml) was chosen. of triethylamine (12.5 ml, 0.09 d) are added pre 110 ° C to a solution of phosphorus pentoxide (25.5 g, 0.09 1-1) in diethyl phosphite (92 ml) After 20 minutes at 90 ° C, Z is added. solution of arginine hydrochloride (27.7 g, 0.09 Ll) in diethyl phosphite (92 ml) containing 35 5 phosphoric acid (10.4 g, 0.09 II), evaporate for 2 hours at 110 ° C, evaporate (1 torso, bath temperature 60 ° C). to the oily residue add 910 ml of 1 II hydrochloric acid and stir at 90 ° C. Upon cooling, the product crystallizes. Maintain 13 hours at 4 ° C, filter. Dissolve in boiling methanol (2500 ml), decolorize with charcoal, filter and concentrate until crystallization begins. Yield: 25.4 g (52 3). K.p. 213 ° C (sat.) Io (j0 - 17.0 (c = 1; 11.11).
Prototipa metodes galvenie trūkumi iri* 1) zemais produkta iznākums, 2) tehnoloģiski sarežģīts risinājums, 3) indīgu un deficītu reaģentu pielietojums. Pēc prototips metodes savienojuma I iznākums ir 52 ... i ol- noThe main disadvantages of the prototype method are * 1) low product yield, 2) technologically complex solution, 3) use of toxic and deficient reagents. According to the prototype method, the yield of compound I is 52 ... i
Šajā metodē d.ietilfosfīts - ļoti indīgs fosfora organ savienojumu klases pārstāvis - lietots gan kā kumurīna grupu aktivējošs aģents,gan kā šķīdinātājs. Dictilfonf īHIn this method, d.ethyl phosphite, a highly toxic member of the class of organophosphorus compounds, is used both as a coumarin activating agent and as a solvent. Dictilfonf HH
BAD OBIGINALBAD OBIGINAL
L LV 10943 iegūšanai nepieciešama papildus sintēzes stadija - to iegūst no fosfora trihlorīda un etanola -5+0°C temperatūrā ar sekojošu destilāciju vāks.urnā ( 10 mm Hg: st.).L LV 10943 requires an additional synthesis step - it is obtained from phosphorus trichloride and ethanol at -5 + 0 ° C with subsequent distillation in a lid (10 mm Hg: h).
Prototipa metode ir sarežģīta tehnoloģiskā ziņā: 1) noteikta konkrēti viena temperatūra, kurā jāveic dotā operācija (fosfora pentoksīda pievienošana pie 110°C; Z-arginīna hidrogenhlorīda pievienošana pie 90°C); 2) nepieciešama reakcijas maisījuma iztvaicēšana pie 50°/l tors =1 mm Hg st.).The prototype method is complicated in technological terms: 1) the specific temperature at which a given operation has to be performed (addition of phosphorus pentoxide at 110 ° C; addition of Z-arginine hydrochloride at 90 ° C); 2) Evaporation of reaction mixture at 50 ° / l tors = 1 mm Hg h) is required.
Piedāvātais izgudrojums novērš visus prototipa trūkumus un ļauj iegūt S-arginīna 4- metilkunaril-7-anīdu tehnoloģiski vienkāršā procesā bez indīgā dietilfosf.īmc pielietošanas. ‘Tas panākts 7-amino—k-metilkumarīna suspensiju piridīnā maisot 1 stundu ar fosfora trihlorīda piridīnā, sekojošu 17-benziloksikarbonilarginīna hidrogenhlorīca šķīduma piridīnā pievienošanu, 3-4 stundu sildīšanu 40-50°C temperatūra, izturēšan 10 stundas istabas temperatūrā, piridīnā atdestliešanu, apstrādi ar 1 7T sālsskābi, pārkristalizēšanu no netanola/dine-t i1fo rmanīd a (4:1). Z—Arg-lIKii (I) iegūšana no 7— e.mino—mctilkumarīna un Z-arginīna hidrogenhlorīda, izmantojot fosfora trihlorīda un piridīnu, literatūrā nav aprakstīta.The present invention overcomes all of the shortcomings of the prototype and allows the preparation of S-arginine 4-methylcunoyl-7-anide in a technologically simple process without the use of poisonous diethylphosphine. This was achieved by stirring a suspension of 7-amino-k-methylcoumarin in pyridine for 1 hour with phosphorus trichloride in pyridine, followed by the addition of a solution of 17-benzyloxycarbonylarginine hydrochloride in pyridine, heating for 3-4 hours at 40-50 ° C, refluxing for 10 hours, treatment with 1 7T hydrochloric acid, recrystallization from netanol / dine-t-1 R (4: 1). Preparation of Z-Arg-LIKii (I) from 7-e.mino-methylcumacumarin and Z-arginine hydrochloride using phosphorus trichloride and pyridine is not described in the literature.
Izgudrojumā piedāvātā metode nodrošina Sģ ,,3-īgu saviono-’una I iznākumu. Lintēzc tiek veikta vienā stadijā, izslēdzot dietilforfati 0 C~ — 0 ošanu un atd·: stilej o_ udensstruklas sūkņa vakuumā (gO-4C mm Hg st.); prototipa 1 mr. Hg st. ) . BAD ORIGINAL L.. ..The method provided by the invention provides a S, 3-fold, and I yield. The lintesc is carried out in a single step, with the exclusion of diethylformate at 0 C ~ - 0 and refluxing in a vacuum pump (gO-4C mm Hg st); prototype 1 mr. Hg st. ). BAD ORIGINAL L .. ..
LV 10943LV 10943
Izgudrojurna būtība ilustrē izgudrojuma eksperimenta •praksts: suspensijai 20 ml fosfora trihlorīda pievieno 17,2 g 17,5 £ (0,1 '*) 7-smino-4-metilkunarīna piridīna maisot piepilina 4,'36 ml (0,05 šķīduma 20 ml piridīna. 1 stundu maisa, tad (0,005 īi) s-argimna Ivlaisījumu silda 5-4 hidrogenhlonda šķīduma 50 ml piridīna. stundas 40-50°C temperatūrā, tad atstāj 10 stundas. Atdestilē piridīnu pie pazemināta spiediena (50-40 mm Hg st., vannas temperatūrā 40°C). bļļu šķīdina 100-120 ml etanola. Filtrē, nogulsnēm pievieno 70-100 ml 1 Ϊ! sālsskābes un maisa 1 stundu uz magnētiskā maisītāja. Filtrē. Kristalizē no natanola/^imetilfDrmamīda (4:1) maisījuma.The essence of the invention is illustrated by the inventive experimental protocol: 17.2 g of 17.5 £ (0.1 '*) of 7-smino-4-methylcunnarine pyridine are added to a suspension of 20 ml of phosphorus trichloride with stirring, 4.36 ml (0.05 of a solution of 20 ml). of pyridine, stir for 1 hour, then (0.005 liter) s-argimna The mixture is heated with 5-4 Hydrochloride solution in 50 ml of pyridine for 40 hours at 40-50 ° C, then left for 10 hours Distill the pyridine under reduced pressure (50-40 mm Hg) Dissolve 100-120 ml of ethanol in a bath, filter, add 70-100 ml of 1 L hydrochloric acid to the precipitate and stir on a magnetic stirrer for 1 hour. Crystallize from natanol / 4-dimethylamide (4: 1). ) mixture.
Iegūst 20,8 g (35 %) savienojuma I. K.p. 212-214°C;ļ( 0{ J 17,0 (c=2; DI.iF) · Hroraatogrāf iski viendabīgs sistēmā - hloroforms: metanols:etiķskābe:ūdens=20:5:0,5:0,5.20.8 g (35%) of compound I.K.p. 212-214 ° C; (0 {J 17.0 (c = 2; DI.iF) · Chloroform is homogeneous in the system - chloroform: methanol: acetic acid: water = 20: 5: 0.5: 0.5).
LITERATŪRA 1. Zimmerman Γ.Ι., Asche 3. - Anal.3iochen., 1978, vol.78, p. 47-51. 2. CakaKHgapa c. 3aHBKa ΤΙποηηη .7" 54-3074; ΡΗΧ, 4 021 Π, 1980. "Πρ0Μ3Β0ΛΗΗβ πθπτι^οβ”LITERATURE 1. Zimmerman Γ.Ι., Asche 3. - Anal.3iochen., 1978, vol.78, p. 47-51. 2. CakaKHgapa c. 3aHBKa ΤΙποηηη .7 "54-3074; ΡΗΧ, 4,021 Π, 1980. " Πρ0Μ3Β0ΛΗΗβ πθπτι ^ οβ ”
Kanaoka 2., Takahashi Oalcakibara 0. - Chem, T., lTakayama H., Takaaa K., Kimura T Pharn. Buli., 1977, vol. 25, p.5126- * 4. Kharamungkhune 0., Sigler G. - Svnthecis, 1980, vol.8, p. 614-615. 5. ilosflHes B.šž. A.c. 1432983 CCCP. "Cnocotf noJivtreHHtf apigi- aMMflOB aam,M't8HHoro aprMHHHa"Kanaoka 2., Takahashi Oalcakibara 0. - Chem, T., lTakayama H., Takaaa K., Kimura T Pharn. Buli., 1977, vol. 25, p.5126- * 4. Kharamungkhune 0., Sigler G. - Svnthecis, 1980, vol.8, p. 614-615. 5. ilosflHes B.sh. A.c. 1432983 CCCP. " Cnocotf noJivtreHHtf apigi- aMMflOB aam, M't8HHoro aprMHHHa "
BAD ORIGINAL L.........BAD ORIGINAL L ..........
VV
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LV940085A LV10943B (en) | 1994-04-26 | 1994-04-26 | Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LV940085A LV10943B (en) | 1994-04-26 | 1994-04-26 | Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine |
Publications (2)
Publication Number | Publication Date |
---|---|
LV10943A LV10943A (en) | 1995-12-20 |
LV10943B true LV10943B (en) | 1996-08-20 |
Family
ID=19735739
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LV940085A LV10943B (en) | 1994-04-26 | 1994-04-26 | Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine |
Country Status (1)
Country | Link |
---|---|
LV (1) | LV10943B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102272596B (en) * | 2009-01-08 | 2014-10-01 | 帕普斯特许可有限两合公司 | Method and device for measuring the activity of enzymes after inhibitor removal |
-
1994
- 1994-04-26 LV LV940085A patent/LV10943B/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102272596B (en) * | 2009-01-08 | 2014-10-01 | 帕普斯特许可有限两合公司 | Method and device for measuring the activity of enzymes after inhibitor removal |
Also Published As
Publication number | Publication date |
---|---|
LV10943A (en) | 1995-12-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tager et al. | 2-Aminonorbornane-2-carboxylic acid. Preparation, properties, and identification of the four isomers | |
US6794537B1 (en) | Manufacturing processes for Se-methyl-L-selenocysteine | |
DeWald et al. | 6-diazo-5-oxo-l-norleucine, a new tumor-inhibitory substance. 1a preparation of l-, d-and dl-forms1b | |
Robertson et al. | Preparation, Resolution and Optical Stability of 3, 4-Dehydroproline and 3, 4-Dehydroprolinamide | |
Ishida et al. | Molecular design of functional peptides by utilizing unnatural amino acids: toward artificial and photofunctional protein | |
LV10943B (en) | Method for preparation of 7-(n-benzyloxycarbonyl)arginylamido-4-methylcoumarine | |
US5888829A (en) | Photolabile caged ionophores and method of using in a membrane separation process | |
Shen et al. | Synthesis of new diselenide compounds as anti-inflammatory agents | |
Dollinger et al. | [48] Bacteriorhodopsin: Fourier transform infrared methods for studies of protonation of carboxyl groups | |
JPH0546332B2 (en) | ||
CN114736153A (en) | AIE type azozyme fluorescent small-molecule probe and preparation method thereof | |
Gu et al. | A practical synthesis of ethyl L-glutamine (L-theanine) | |
Garssen et al. | NMR studies of the interaction of gene-V protein of bacteriophage M13 with oligonucleotides | |
RU2132841C1 (en) | Method of purifying oxytetracycline, and intermediate product | |
KR20130093078A (en) | A PROCESS FOR THE PRODUCTION OF CARNITINE FROM β-LACTONES | |
FR2558481A1 (en) | PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE 4-AMINO-3-HYDROXYBUTYRIC ACID | |
JPH05336979A (en) | Production of p-hydroxybenzoic acid | |
JPH05328981A (en) | Production of para hydroxybenzoic acid | |
Neuberger et al. | Synthesis and metabolism of some substances related to δ-aminolaevulic acid | |
CN113004886B (en) | Preparation method and application of benzoquinolines ratio type near-infrared fluorescent molecular probe for fluorine ion detection | |
CN114989068B (en) | Hydrogen sulfide response fluorescent probe capable of regulating electron density and preparation process and application thereof | |
EP0251327B1 (en) | Process for production of anthracycline compound r2ox2 | |
JP3030896B2 (en) | WB968 substance group and production method thereof | |
FR2479260A1 (en) | PROCESS FOR SEPARATING AND RECOVERING COPROPORPHYRIN AND UROPORPHYRIN FROM A CULTURE BROTH | |
US4370415A (en) | Process for producing uroporphyrin III |