Scopolamine butylbromide(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/scopolamine-butylbromide-cas-149-64-4.html) yog ib qho tshuaj siv los kho cov tsos mob ntawm plab hnyuv, thiab nws cov qauv tshuaj zoo ib yam li Scopolamine hydrobromide. Rau cov kws tsim tshuaj, nrhiav kev ua kom zoo thiab ua tau zoo tuaj yeem ua tsis tau tsuas yog txo cov nqi tsim khoom, tab sis kuj ua kom cov khoom zoo thiab tawm los.
Traditional chemical synthesis method:
1.1 Synthetic route ib:
Cov txheej txheem hluavtaws los ntawm cov ntaub ntawv tshawb fawb ("Synthesis of buscopan derivatives"), cov kauj ruam tseem ceeb yog raws li hauv qab no:
Kauj Ruam 1: Cov tshuaj tiv thaiv ntawm 2-bromoisopropylacetophenone nrog N-methyl-2-pyridinecarboxamide:
Sib tov 2-bromoisopropylacetophenone nrog N-methyl-2-pyridinecarboxamide thiab hnov mob ntawm 85 degree rau ob peb teev nyob rau hauv lub xub ntiag ntawm cesium chloride kom tau cov khoom.
Kauj Ruam 2: Cov tshuaj tiv thaiv ntawm 2-bromoisopropyl-N-methyl-2-pyridinecarboxamide nrog propylene oxide:
Cov khoom saum toj no yog tov nrog propylene oxide thiab nplawm ntawm chav tsev kub nyob rau hauv lub xub ntiag ntawm sodium hydroxide rau ob peb teev kom tau Scopolamine butylbromide.
Qhov zoo ntawm txoj kev siv hluavtaws no yog cov tshuaj tiv thaiv me me, thiab tsis tas yuav siv ntau cov kuab tshuaj lom thiab teeb meem thiab cov tshuaj reagents. Txawm li cas los xij, kev sib cais thiab kev ua kom huv ntawm cov txheej txheem no yog qhov nyuaj, thiab cov txiaj ntsig tsis zoo.
1.2 Synthetic route ob:
Txoj kev hluavtaws yog muab los ntawm cov ntaub ntawv patent (US Patent 4418109 A), thiab cov kauj ruam tseem ceeb yog raws li hauv qab no:
Kauj Ruam 1: Cov tshuaj tiv thaiv cis-4-hydroxy-3-methoxyphenylacetic acid nrog 2,3-dibromopropionyl bromide:
cis-4-hydroxy-3-methoxyphenylacetic acid yog tov nrog 2,3-dibromopropionyl bromide thiab reacted rau ob peb teev ntawm chav tsev kub nyob rau hauv lub xub ntiag ntawm ethanol muab 2-({{5 }}hydroxy-3-methoxy phenylacetic acid)-2, 3-dibromopropyl ester.
Kauj Ruam 2: Recrystallization ntawm 2-(4-hydroxy-3-methoxyphenylacetic acid)-2, 3-dibromopropyl ester:
Cov khoom saum toj no tau recrystallized kom tau txais cov khoom lag luam nrog ntau dua purity.
Kauj Ruam 3: Cov tshuaj tiv thaiv ntawm 2-(4-hydroxy-3-methoxyphenylacetic acid) propionamidine nrog metabromic acid:
Sib tov 2-(4-hydroxy-3-methoxyphenylacetic acid) propionamidine nrog metabromide thiab hnov mob hauv chav sov li ob peb teev nyob rau hauv muaj ethanol kom tau Scopolamine butylbromide.
Qhov kom zoo dua ntawm txoj kev siv hluavtaws no yog qhov kev sib cais thiab kev ua kom huv huv yog qhov ua tau zoo, cov khoom muaj purity siab, thiab cov txiaj ntsig zoo tshaj plaws. Txawm li cas los xij, cov kev mob tshwm sim kuj hnyav heev thiab yuav tsum muaj qee yam kev sim tshuaj lom neeg.
Txoj kev enzymatic synthesis:
2.1 Synthetic route peb:
Cov txheej txheem hluavtaws los ntawm cov ntaub ntawv tshawb fawb luam tawm hauv Phau Ntawv Xov Xwm ntawm Molecular Catalysis B: Enzymatic ("Enzymatic synthesis ntawm scopolamine butyl bromide ntawm thermophilic esterase"), cov kauj ruam tseem ceeb yog raws li hauv qab no:
Kauj ruam 1: Synthesis ntawm 2-(4-hydroxy-3-methoxyphenylacetic acid) propionyl chloride:
Sib tov 2-(4-hydroxy-3-methoxyphenylacetic acid) nrog propionyl chloride thiab hnov mob ntawm chav tsev kub rau ob peb teev nyob rau hauv muaj cov catalyst kom tau txais 2-({{4} }hydroxy-3-methoxyphenylacetic acid) propionyl chloride acid chloride.
Kauj Ruam 2: Cov tshuaj tiv thaiv ntawm 2-(4-hydroxy-3-methoxyphenylacetic acid) propionyl chloride nrog n-butylammonium bromide.
Cov khoom saum toj no yog tov nrog n-butylammonium bromide, thiab nyob rau hauv lub xub ntiag ntawm phosphate tsis, nyob rau hauv qhov tsim nyog kub thiab pH tej yam kev mob, enzyme Thermomyces lanuginosus lipase (TLL) nrog siab thermal stability yog siv los catalyze cov tshuaj tiv thaiv kom tau Scopolamine butylbromide.
Piv nrog rau thawj ob txoj kev siv tshuaj synthesis, txoj kev hluavtaws no muaj cov tshuaj tiv thaiv me me thiab kev xaiv zoo dua thiab tawm los. Txawm li cas los xij, txoj kev no muaj cov kev xav tau siab rau catalysts thiab enzymes, thiab qee qhov txheej txheem yuav tsum tau ua kom zoo dua.
Synthesis method sib piv thiab cov ntsiab lus:
Kev txiav txim los ntawm ntau txoj kev siv hluavtaws ntawm Scopolamine butylbromide tau qhia saum toj no, cov txheej txheem tshuaj lom neeg cov tshuaj thiab cov txheej txheem enzymatic synthesis muaj lawv tus kheej qhov zoo thiab qhov tsis zoo. Cov txheej txheem tshuaj synthesis yog ib qho yooj yim thiab yooj yim, tab sis cov tshuaj tiv thaiv kuj hnyav heev, thiab kev sib cais thiab kev ua kom huv yog cumbersome. Txoj kev enzymatic synthesis muaj cov tshuaj tiv thaiv me me, kev xaiv siab thiab tawm los, tab sis yuav tsum muaj kev ua haujlwm siab enzyme thiab catalyst purity, thiab ntxiv cov txheej txheem optimization yog yuav tsum tau.
Hauv kev xaus, cov txheej txheem hluavtaws ntawm Scopolamine butylbromide tseem ntsib qee qhov teeb meem thiab teeb meem. Txawm li cas los xij, nrog kev txhim kho ntawm biotechnology thiab tshuaj synthesis thev naus laus zis, nws ntseeg tau tias muaj txiaj ntsig zoo dua, ib puag ncig tus phooj ywg, thiab cov txheej txheem sib xyaw ua tau zoo yuav raug tshawb pom thiab txhawb nqa, yog li muab cov txiaj ntsig zoo dua rau kev lag luam loj ntawm Scopolamine butylbromide.
Scopolamine butylbromide yog ib qho nyuaj organic compound nrog cov mis mos molecular C21H30BrNO4. Nws belongs rau cov chav kawm dimethyloxymuscarinic ntawm cov tshuaj, zoo ib yam li atropine, tab sis piv nrog atropine, nws bromide ion hloov cov pab pawg hydroxyl.
1. Molecular qauv:
Cov qauv molecular ntawm Scopolamine butylbromide muaj cov qauv carboxylic acid monoester (COOCH2CH2CH2CH3) thiab cov qauv benzyloxycarbonyl (C6H5CH2OCO) uas muaj bromine atom. Ntawm lawv, pawg benzyl thiab pawg methyl txuas nrog rau carbonyl los ua ib lub nplhaib rau rau tus tswv cuab, thiab lub nplhaib rau lub nplhaib txuas nrog rau lwm tsib lub nplhaib. Muaj ib pawg txiv neej nrog peb hydrogen atoms, ib pawg amino thiab ib lub pa oxygen atom ntawm tsib lub nplhaib. Nyob rau hauv cov qauv imine, cov atoms nyob rau hauv plaub txoj haujlwm sib txawv ntawm tsib lub nplhaib yog txuas nrog ntau pawg, raws li qhia hauv daim duab:
Cov qauv molecular no ua rau Scopolamine butylbromide muaj cov nyhuv anticholinergic zoo ib yam li ntawm atropine, thiab tib lub sijhawm, kev hloov pauv ntawm bromine atoms txo cov teebmeem hauv nruab nrab ntawm cov tshuaj atropine. Tsis tas li ntawd, cov qauv ntawm tsib-ntiv nplhaib ib feem kuj endows Scopolamine butylbromide nrog qee yam kev ruaj ntseg.
2. Anticholinergic pharmacological teebmeem:
Scopolamine butylbromide yog ib qho tshuaj anticholinergic, thiab nws cov nyhuv feem ntau yog ua kom tsis muaj zog ntawm acetylcholine los ntawm kev sib tw antagonizing qhov kev txiav txim ntawm acetylcholine ntawm M1-M5 receptors. Nyob rau hauv lub plab zom mov, Scopolamine butylbromide tuaj yeem so cov leeg du, txo cov dej tso tawm, thiab muaj kev kho mob ntawm kev zom zaub mov, plab tsis xis nyob thiab lwm yam kab mob. Nyob rau hauv lub cev muaj zog, Scopolamine butylbromide tuaj yeem txo cov leeg nqaij, thiab muaj qee yam cuam tshuam rau kev txo cov kab mob hauv lub cev xws li spastic torticollis. Tsis tas li ntawd, hauv kev ua pa, Scopolamine butylbromide tuaj yeem siv los ua bronchodilator.
3. Pharmacokinetics:
Scopolamine butylbromide tuaj yeem nkag mus rau hauv lub cev los ntawm txoj hnyuv thiab cov hlab ntsha hauv hlwb tom qab kev tswj hwm qhov ncauj lossis txhaj tshuaj. Hauv plab hnyuv, nws nqus tau sai heev, ncav cuag cov ntshav siab nyob rau hauv li ntawm 1-2 teev, thiab mus txog qib ntshav siab tshaj plaws hauv 0.5-1 teev tom qab txhaj tshuaj. Qhov ncauj Scopolamine butylbromide feem ntau yog metabolized los ntawm daim siab, qhov twg nws yog acylated los yog hydroxylated los tsim cov metabolites sib xws, uas tom qab ntawd tawm hauv lub cev los ntawm ob lub raum lossis cov kua tsib. Kev txhaj tshuaj ntawm Scopolamine butylbromide yog yooj yim metabolized thiab tawm los ntawm ob lub raum. Feem ntau, cov metabolism thiab tshem tawm Scopolamine butylbromide hauv lub cev yog qhov nrawm, thiab nws ib nrab-lub neej yog nyob nruab nrab ntawm 2-4 teev.
Hauv cov ntsiab lus, Scopolamine butylbromide yog cov organic compound nrog cov qauv nyuaj thiab muaj zog lom neeg ua haujlwm, uas muaj ntau yam teebmeem anticholinergic. Nws cov qauv molecular muaj cov qauv benzyloxycarbonyl thiab carboxylic acid monoester qauv, uas yog lub hauv paus tseem ceeb rau nws cov tshuaj anticholinergic pharmacological. Nyob rau hauv cov nqe lus ntawm pharmacokinetics, Scopolamine butylbromide muaj bioavailability zoo thiab metabolic teebmeem, thiab yog dav siv nyob rau hauv kev kho mob xyaum.