Scopolamine hydrobromide(Product link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/scopolamine-hydrobromide-powder-cas-114-49-8.html) yog ib hom tshuaj uas muaj ntau yam kev kho mob xws li anticholinergic, tshuaj loog thiab neuropathic strabismus. Raws li kev sim ntau yam hluavtaws los ntawm Shaanxi Achieve chem-tech Co., Ltd Chemical Laboratory, nws cov qauv tshuaj muaj ntau lub nplhaib, esters thiab hydrolyzed choline glycosides, yog li muaj ntau txoj hauv kev hluavtaws. Kab lus no yuav txheeb xyuas cov hauv paus ntsiab lus, yam ntxwv, qhov zoo thiab qhov tsis zoo ntawm cov txheej txheem no, thiab sib tham txog lawv cov kev siv tshuaj kho mob.
1. Trost synthesis method:
Scopolamine hydrobromide yog cov organic alkaloid uas muaj ntau yam teebmeem xws li anticholinergic, anti-narcotic, anti-depressant, thiab tiv thaiv kev ntxhov siab. Nws yog ib qho tshuaj siv dav hauv cov tshuaj kho mob. Trost synthesis yog ib txoj hauv kev zoo rau kev npaj Scopolamine hydrobromide. Qhov kom zoo dua ntawm txoj kev no yog tias cov tshuaj tiv thaiv mob me me thiab cov txiaj ntsig tau siab, tab sis nws yuav tsum siv cov catalysts thiab reagents kim heev, thiab muaj qee yam kev phom sij thiab kev nyab xeeb.
Lub hauv paus ntsiab lus ntawm Trost synthesis txoj kev yog los ua kom paub qhov yuav tsum tau muaj plaub-ntiv nplhaib qauv rau hauv Scopolamine precursor molecule los ntawm Detroit cov tshuaj tiv thaiv, thiab thaum kawg tau txais Scopolamine hydrobromide. Nov yog cov kauj ruam ntxaws:
(1) Kev npaj ntawm Scopolamine precursor molecule
Ua ntej, Scopolamine precursor molecule yuav tsum tau npaj. Cov molecule precursor no feem ntau tshwm sim nrog atropine thiab chloroacetimide los tsim N-acetyl atropine. Cov tshuaj tiv thaiv tau nqa tawm ntawm chav tsev kub, thiab 1.5 qhov sib npaug ntawm trimethylamine tau ntxiv rau cov tshuaj tiv thaiv los txhawb cov tshuaj tiv thaiv. Tom qab cov tshuaj tiv thaiv, dilute nrog dej, kho cov pH txog li 10 nrog NaOH, tshem tawm cov khoom los ntawm cov tshuaj tiv thaiv, kho cov pH rau 8-9 dua nrog NaOH, thiab thaum kawg tau txais qhov xav tau precursor molecule ntawm Scopolamine.
(2) Qhia txog plaub-tus tswv cuab lub nplhaib
Dissolve lub npaj Scopolamine precursor molecules nyob rau hauv ib tug tov tov ntawm dimethyl sulfoxide (DMSO) thiab dej, thiab ces ntxiv sodium hydroxide (NaOH) ua rau pH ntawm 9-10. Hauv qhov no, tetracycline TIPSO (2,3,4,6-tetra-O-isopropylidene- -D-glucose pentaacetate) thiab sodium acetophenone (NAS) tau ntxiv. Tom qab cov tshuaj tiv thaiv pib, daj Troposfere polyhedral qauv yuav tshwm sim nyob rau hauv cov tshuaj, uas yog ib tug tshiab tsim plaub-ntiv nplhaib qauv.
(3) Cleavage ntawm tetracycline thiab tshem tawm TIPSO
Cov tshuaj tiv thaiv kev cais tawm raug tso tseg kom sawv ntsug li 1 teev, thiab tom qab ntawd qee qhov dej methanol tau ntxiv los txhawb qhov txuas ntxiv ntawm Scopolamine precursor molecules thiab tetracycline TIPSO thiab NAS. Tom qab ntawd, tetracycline TIPSO thiab NAS tau raug tshem tawm nrog cov concentrated hydrochloric acid, thiab sodium hydroxide tau ntxiv rau cov tshuaj kho cov pH rau 8-9. Nws thiaj li ib qho dawb dawb precipitate yuav tsim, uas yog qhov xav tau Scopolamine hydrobromide.
Hauv kev xaus, Trost synthesis zoo heev txhim kho kev ua tau zoo thiab kev ruaj ntseg ntawm Scopolamine los ntawm kev qhia txog plaub-tus tswv cuab lub nplhaib zoo. Txoj kev no yog qhov yooj yim thiab ua tau, thiab yog ib txoj hauv kev tseem ceeb heev rau kev tsim Scopolamine.
2. Robinson synthesis method:
Scopolamine hydrobromide yog ib qho tshuaj anticholinergic siv los kho mob kev mob, kab mob plab, thiab kev txav mus los, thiab lwm yam. Robinson synthesis method yog ib txoj hauv kev zoo rau kev sib txuas ntawm Scopolamine hydrobromide. Txoj kev yog los tsim ib lub nplhaib plaub-tus tswv cuab los ntawm ob lub ntsiab lus tseem ceeb, thiab hloov nws mus rau hauv Scopolamine hydrobromide nrog hydrobromic acid. Cov hauv qab no yog cov kauj ruam ntxaws:
(1) Synthesis ntawm 2-methoxycarbonylpyridine-5-carboxylic acid
Ua ntej, nws yog ib qho tsim nyog los npaj 2-methoxycarbonylpyridine-5-carboxylic acid, uas yog ib qho khoom nruab nrab ntawm Scopolamine hydrobromide. Cov tshuaj tiv thaiv yuav tsum tau 2-hydroxypyridine thiab acetyl chloride ua cov khoom pib thiab yog ua nyob rau hauv lub xub ntiag ntawm lub hauv paus. Ua ntej ntxiv sodium hydroxide dropwise rau 2-hydroxypyridine nrog acetone los tsim sodium ntsev, thiab tom qab ntawd ntxiv acetyl chloride. Tom qab cov tshuaj tiv thaiv tiav, acidification muab 2-methoxycarbonylpyridine-5-carboxylic acid.
(2) Kev npaj ntawm 7-methoxycarbonylpyridin[4,3-e]-1,2,4-triazol-8(1H)-ib los ntawm cyclization
Tom ntej no, koj yuav tsum siv 2-methoxycarbonylpyridine-5-carboxylic acid los ua ke 7-methoxycarbonylpyridin[4,3-e]-1,2,4- triazol-8(1H)-ib, Scopolamine hydrobromide precursor molecules. Cov kauj ruam no yog ua los ntawm Robinson nplhaib kaw cov tshuaj tiv thaiv. Ua ntej, NaOEt tau ntxiv rau hauv ethanol, thiab 2-methoxycarbonylpyridine-5-carboxylic acid tau yaj nrog ethyl acetate. Tom qab ntawd ib qho me me ntawm aldehyde catalyst yog ntxiv rau cov reactant, thiab cov catalyst ua tus pib ntawm cov reactant. Raws li cov tshuaj tiv thaiv tshwm sim, qhov tsim ntawm cyclic compounds yuav tshwm sim ntau dua. Nyob rau hauv cov txheej txheem no, nws yog ib qho tsim nyog yuav tsum tau xyuam xim rau tej yam xws li cov concentration ntawm cov reactant, lub sij hawm cov tshuaj tiv thaiv, tus nqi ntawm cov catalyst ntxiv, thiab cov kev xaiv ntawm cov kuab tshuaj, thiaj li hais tias cov tshuaj tiv thaiv yuav tswj tau.
(3) Kev npaj ntawm Scopolamine hydrobromide los ntawm kev txo qis hydrogenation
Thaum kawg, 7-methoxycarbonylpyridin[4,3-e]-1,2,4-triazol-8(1H)-ib qho yuav tsum tau hloov mus rau Scopolamine hydrobromide. Qhov no tuaj yeem ua tiav los ntawm kev txo cov tshuaj tiv thaiv hydrogenation, feem ntau nyob rau hauv acidic tej yam kev mob. Ua ntej, muab 7-methoxycarbonylpyridin[4,{11}}e]-1,2,4-triazol-8(1H)-one thiab PtO2 ua catalyst rau hauv cov tshuaj tiv thaiv lub raj mis, tom qab ntawd ntxiv hydrogen, thiab hnov mob li 6 teev. Cov tshuaj tiv thaiv tau muab rho tawm nrog ethyl acetate thiab pH tau hloov kho nrog NaOH, thiab tom qab ntawd yaj nrog hydrobromic acid los tsim qhov xav tau Scopolamine hydrobromide.
Hauv kev xaus, Robinson synthesis txoj kev tsim cov plaub-ntiv nplhaib qauv ntawm Scopolamine hydrobromide los ntawm ob theem tseem ceeb cov tshuaj tiv thaiv, uas yog Robinson nplhaib kaw cov tshuaj tiv thaiv thiab txo cov tshuaj tiv thaiv hydrogenation, thiab thaum kawg ua tiav zoo synthesizes Scopolamine hydrobromide. Robinson synthesis txoj kev muaj cov yam ntxwv ntawm cov tshuaj tiv thaiv tsawg dua cov kauj ruam thiab kev ua haujlwm yooj yim, tab sis nws yog ib qho yooj yim kom muaj kuab paug, tawm los yog tsawg, thiab xav tau ntau reagents. Nws yog ib txoj hauv kev zoo rau kev npaj Scopolamine hydrobromide.
3. Enzymatic synthesis txoj kev:
Enzymatic synthesis yog ib txoj hauv kev tshiab thiab tus phooj ywg ib puag ncig rau kev ua kom zoo ntawm Scopolamine hydrobromide nyob rau hauv cov xwm txheej me me. Enzymatic synthesis yog hais txog cov txheej txheem ntawm kev siv enzyme catalysis los txhawb cov organic synthesis cov tshuaj tiv thaiv, yog li ua tau zoo thiab xaiv cov phiaj xwm molecules. Sib txawv ntawm cov txheej txheem tshuaj synthesis ib txwm muaj, cov txheej txheem enzymatic synthesis muaj qhov zoo ntawm kev ua haujlwm siab, greenness, mildness, thiab lwm yam, thiab muaj cov yam ntxwv ntawm cov khoom siab purity thiab me me sab, yog li nws tau txais kev saib xyuas thiab kev tshawb fawb.
Lub enzymatic synthesis ntawm Scopolamine hydrobromide yog catalyzed los ntawm tej yam ntuj tso enzymes, uas yog heev tshwj xeeb tej yam ntuj tso enzymes uas muaj peev xwm zoo catalyze tsim amide bonds ntawm carboxyl thiab amino pawg nyob rau hauv Scopolamine hydrobromide molecules. Cov kauj ruam tshwj xeeb ntawm enzymatic synthesis ntawm Scopolamine hydrobromide yog raws li nram no:
Kauj Ruam 1: Pretreatment enzyme
Ua ntej, enzyme pretreatment ntawm Scopolamine hydrobromide yog yuav tsum tau mus qhib thiab stabilize lub enzyme. Cov txheej txheem kev kho mob feem ntau suav nrog cov kauj ruam ntawm enzyme extraction, refining, concentration thiab khov-drying, uas tuaj yeem txhim kho cov catalytic efficiency thiab catalytic stability ntawm enzyme.
Kauj Ruam 2: Kho lub substrate ua ntej cov tshuaj tiv thaiv
Ntxiv cov substrate xav tau los ua ke Scopolamine hydrobromide rau hauv cov tshuaj tiv thaiv kab mob. Lub substrate yuav tsum tau kho ua ntej, thiab los ntawm qee cov tshuaj tiv thaiv, nws tuaj yeem ua ke zoo dua nrog cov tshuaj tiv thaiv enzyme thiab tsim ib qho nyuaj. Feem ntau, substrate pretreatment tuaj yeem ua tiav los ntawm txoj kev xws li agarose gel kem chromatography lossis cross-linked affinity chromatography.
Kauj Ruam 3: Cov tshuaj tiv thaiv Enzymatic
Cov tshuaj substrate pretreated thiab pretreated enzyme yog sib xyaw ua ke thiab reacted nyob rau hauv tsim nyog cov tshuaj tiv thaiv. Cov kev mob tshwm sim feem ntau suav nrog ntau yam xws li pH tus nqi, qhov kub thiab txias, lub sijhawm tshuaj tiv thaiv, thiab cov tshuaj reactant concentration. Cov tshuaj tiv thaiv kab mob yuav tsum tau khaws cia rau hauv qhov kub thiab txias thiab pH ntau kom ua tiav cov enzyme catalytic zoo tshaj plaws. Lub sij hawm cov tshuaj tiv thaiv txawv nyob ntawm qhov concentration ntawm cov reactants, thiab lub sij hawm dav dav yog li ob peb teev.
Kauj Ruam 4: Xaus cov tshuaj tiv thaiv
Thaum cov tshuaj tiv thaiv dhau lawm, qee txoj kev yuav tsum tau siv los kho cov tshuaj tiv thaiv kab mob. Feem ntau hais lus, cov tshuaj tiv thaiv kab mob tuaj yeem kho nrog hnyav, evaporation lossis qee yam tshuaj kom tshem tawm cov khoom tsis zoo thiab ua kom cov khoom ntshiab dua.
Kauj Ruam 5: Tshem tawm thiab ntxuav cov khoom
High-purity Scopolamine hydrobromide cov khoom lag luam tuaj yeem tau txais los ntawm kev sib cais thiab kev ua kom huv, xws li countercurrent distillation, extraction, kem chromatography, thiab lwm yam.
Qhov zoo ntawm Scopolamine hydrobromide enzymatic synthesis txoj kev:
(1) Ib puag ncig tus phooj ywg thiab ntsuab: Piv nrog cov tshuaj siv tshuaj sib xyaw ua ke, cov tshuaj enzymatic tsis tas yuav muaj cov kuab tshuaj lom thiab muaj teeb meem loj, cov tshuaj reagents thiab lwm yam tshuaj, yog li nws yog ib puag ncig zoo thiab ntsuab.
(2) Kev xaiv tau zoo: Txoj kev enzymatic synthesis tuaj yeem ua kom muaj txiaj ntsig zoo rau kev sib txuas ntawm cov khoom lag luam thiab muaj kev xaiv siab, yog li nws tuaj yeem txo cov khoom pov tseg thiab tus nqi ntawm cov enzyme catalyst siv.
(3) Cov khoom purity siab: Cov khoom tsim los ntawm cov txheej txheem enzymatic synthesis muaj siab purity thiab tsis muaj impurity cov ntsiab lus, yog li tsis tas yuav tsum muaj cov kauj ruam purification ntxiv, uas tuaj yeem txuag sijhawm thiab nqi.
(4) Cov tshuaj tiv thaiv me me: Cov kev mob tshwm sim ntawm cov txheej txheem enzymatic synthesis yog me me, thiab cov tshuaj tiv thaiv kub feem ntau nyob nruab nrab ntawm chav tsev kub thiab 40 degree, yog li nws tuaj yeem tswj hwm lub ntuj tsim thiab kev ua haujlwm ntawm lub cev ntawm cov tshuaj tiv thaiv substrate thiab ua haujlwm zoo. peb-dimensional configuration ntawm tus thawj molecule thiab lub ntsiab muaj nuj nqi.
(5) Lub zeem muag dav dav rau kev lag luam kev lag luam: Enzyme yog biocatalyst uas dav muaj nyob rau hauv cov xwm txheej thiab muaj kev siv dav dav. Vim tias qhov kev thov loj rau Scopolamine hydrobromide, kev lag luam dav dav thiab cov txiaj ntsig tseem ceeb ntawm kev lag luam, cov enzymatic synthesis ntawm Scopolamine hydrobromide muaj qhov zoo ntawm kev cia siab rau kev lag luam industrialization.
Nyob rau hauv xaus, lub enzymatic synthesis ntawm Scopolamine hydrobromide yog ib tug npaum, environmentally friendly, high-selectivity, high-purity hluavtaws txoj kev nrog dav daim ntawv thov prospects. Txoj kev no tuaj yeem muab txoj hauv kev tshiab rau kev tsim khoom ntawm Scopolamine hydrobromide.