Epinephrine Hydrochlorideyog dawb crystalline hmoov. Nws cov tsos tuaj yeem raug txiav txim los ntawm kev soj ntsuam nws cov xim, cov duab thiab qhov loj me. Cov tsos mob ntawm DL-ADRENALINE HYDROCHLORIDE yog tshwm sim los ntawm cov yam ntxwv xws li purity, txoj kev npaj thiab cia. Soluble nyob rau hauv dej, muaj peev xwm tsim ib tug ntshiab tov. Nws kuj yog soluble hauv qee cov kuab tshuaj organic xws li methanol thiab chloroform. Nws solubility yog txuam nrog kub thiab pH nqi. Lub refractive index yog 1.57. Qhov Performance index ntawm refraction yog qhov degree uas lub teeb yog deflected thaum nws mus los ntawm huab cua mus rau ib yam khoom. Kev ntsuas ntawm qhov ntsuas qhov ntsuas tsis zoo tuaj yeem siv los txiav txim siab purity thiab qauv ntawm cov khoom. yog ib qho tseem ceeb compound siv nyob rau hauv biological, kev kho mob thiab tshuaj tshawb fawb. Cov tshuaj ntawm cov khoom kawg no yog siv dav hauv kev kho mob ntawm cov kab mob plawv, kev kho mob hawb pob, tshuaj loog hauv zos thiab lwm txoj kev kho mob. Txawm li cas los xij, nws yuav tsum raug sau tseg tias cov khoom no yog cov khoom siv tshuaj lom neeg thiab tsuas yog siv rau kev tshawb fawb txog kev tshawb fawb.
Kab lus no yuav tham txog ntau txoj hauv kev hluavtaws ntawm DL-epinephrine hydrochloride:
1. Noradrenaline rau Adrenaline rau DL-epinephrine hydrochloride synthesis method:
Txoj kev sib txuas no yuav tsum pib los ntawm Noradrenaline, thiab los ntawm qhov sib xyaw nruab nrab (4-Methoxyphenylacetone), nyob rau hauv catalysis ntawm cov khoom noj khoom haus additives, ob qho kev cuam tshuam hloov Noradrenaline rau hauv Adrenaline. Adrenaline tom qab ntawd raug rau alkylation thiab N-Boc deprotection nrog kev tiv thaiv ntawm pab pawg OH muab DL-adrenaline hydrochloride.
1.1. Synthesis ntawm Noradrenaline rau Adrenaline:
Noradrenaline yog ib qho tseem ceeb neurotransmitter, thiab nws txoj kev hluavtaws hauv tib neeg lub cev feem ntau yog los ntawm kev ua ntawm dopamine -hydroxylase los catalyze hloov dua siab tshiab ntawm dopamine. Copper ions hauv dopamine -hydroxylase ua lub luag haujlwm tseem ceeb hauv cov tshuaj tiv thaiv no. Thaum lub sij hawm no cov tshuaj tiv thaiv, dopamine yog oxidized rau dopaic acid nyob rau hauv lub catalysis ntawm carboxylase, thiab ces hloov mus rau hauv Noradrenaline nyob rau hauv lub catalysis ntawm dopamine -hydroxylase.
Cov qauv ntawm Noradrenaline zoo ib yam li Adrenaline, tshwj tsis yog tias muaj ib pawg hydroxyl ntxiv hauv cov qauv molecular. Yog li ntawd, nyob rau hauv lub hauv paus ntawm Noradrenaline, Adrenaline tsuas yog tau los ntawm oxidizing hydrogen atoms rau hydroxyl pawg los ntawm enzymatic cov tshuaj tiv thaiv.
1.2. Synthesis ntawm Adrenaline rau DL-epinephrine hydrochloride
Adrenaline yog qhov sib xyaw nrog cov haujlwm tseem ceeb ntawm cov tshuaj, yog li nws tau siv dav hauv cov tshuaj niaj hnub no. Txawm li cas los xij, ob lub chaw chiral hauv Adrenaline yog asymmetric, yog li nws muaj ob isomers, uas yog sab laug thiab sab xis. Tsis tas li ntawd, cov haujlwm pharmacological ntawm ob isomers no txawv heev. Yog li ntawd, tshwj xeeb yuav tsum tau them nyiaj rau kev tswj cov chiral selectivity thaum npaj Adrenaline.
Cov kauj ruam hluavtaws ntawm DL-epinephrine hydrochloride yog raws li nram no:
(1) Oxidation ntawm Adrenaline rau DL-epinephrine los ntawm N-hydroxysuccinimide ua tus neeg sawv cev oxidizing:
Thaum lub sijhawm txheej txheem no, DL-epinephrine tau xub ntxiv rau N-hydroxysuccinimide yaj hauv acetone, nplawm maj mam thiab ua kom sov rau 62-64 degree thaum ntxiv, thiab cov tshuaj tiv thaiv tau khaws cia rau 4 teev. Tom qab cov tshuaj tiv thaiv tiav lawm, cov tshuaj tiv thaiv tau txias rau hauv chav tsev kub, cov amino acid uas tsim tawm tau lim tawm, thiab cov khoom tsim tawm DL-epinephrine hydrochloride raug cais tawm ntawm cov tshuaj tiv thaiv los ntawm cov concentrated HCl.
(2) Purification ntawm DL-epinephrine hydrochloride:
Los ntawm kev ntxiv cov tshuaj sib xyaw ntawm anhydrous hydrochloric acid thiab ethanol rau cov khoom siv tshuaj tiv thaiv, DL-adrenaline hydrochloride yog purified kom tau cov crystals ntawm DL-adrenaline hydrochloride.
Hauv cov ntsiab lus, cov synthesis ntawm Epinephrine Hydrochloride yog qhov pib faib ua ob kauj ruam, thawj zaug yog oxidize Noradrenaline rau Adrenaline, thiab tom qab ntawd oxidize Adrenaline rau DL-epinephrine hydrochloride. Yuav kom tau txais high-purity DL-epinephrine hydrochloride, ntau cov kauj ruam ntawm kev sib cais thiab purification yuav tsum tau.
2. Pyrocatechol yog cov txheej txheem hluavtaws ntawm cov khoom siv raw:
Carandiz synthesis yog ib txoj hauv kev rau kev npaj DL-epinephrine hydrochloride siv Pyrocatechol ua cov khoom pib. Cov kauj ruam ntawm txoj kev yog: hydrolyzing Pyrocatechol nrog FeCl3 rau Hydroquinone, thiab tom qab ntawd nqa tawm cov tshuaj tiv thaiv condensation ntawm Hydroquinone thiab Glyoxylic acid los tsim DL-adrenaline ketal. Lub ketal yog txo rau DL-epinephrine, thiab tom qab ntawd acidified nrog HCl los ua ke DL-epinephrine hydrochloride.
Part 1: Synthesis of Pyrocatechol
Kauj Ruam 1: Oxidation ntawm resorcinol rau benzoquinone
1000 mL dej tau ntxiv rau hauv lub khob peb-caj dab, thiab tom qab ntawd ntxiv 0.05 mol ntawm CuSO4. Maj mam ntxiv 1 mol ntawm NaOH rau pH 8 thaum nplawm. Tom ntej no, 0.25 mol ntawm resorcinol tau ntxiv rau lub khob thiab nplawm, ces rhuab mus rau 80 degree. Ntxiv 0.05mol ntawm CuSO4 hauv batch 3 zaug, thiab txuas ntxiv cua sov thiab nplawm. Thaum lub sij hawm cov tshuaj tiv thaiv, ib tug daj-xim av flocculent precipitate tau pom. Tom qab cov tshuaj tiv thaiv tiav lawm, cov khoom raug lim thiab ntxuav, ces qhuav thiab pulverized rau hauv hmoov.
Kauj Ruam 2: Txo cov benzoquinone rau Pyrocatechol
1000 mL dej tau ntxiv rau hauv lub khob peb-caj dab, tom qab ntawd 0.5 mol ntawm NaBH4 tau ntxiv, thiab cov tshuaj tau nplawm rau 30 feeb. Thaum nplawm, 0.25 mol ntawm benzoquinone tau maj mam ntxiv. Raws li qhov sib ntxiv tau nce, kev hloov pauv hauv cov tshuaj tiv thaiv kinetics thiab xim tau pom. Thaum cov tshuaj tiv thaiv pom pom tseeb xim xim av-liab, tus nqi pH raug kho rau 4-5 nrog 1 mol ntawm HCl. Tom qab ntawd, cov khoom raug lim thiab ntxuav, thiab qhuav kom tau Pyrocatechol.
Part 2: Synthesis ntawm Epinephrine Hydrochloride
Kauj Ruam 1: Hloov Pyrocatechol rau 3, 4-dihydroxyphenylethanol
Cov tshuaj tiv thaiv siv cov tshuaj tiv thaiv Cannizzaro. Dissolve tus nqi ntawm Pyrocatechol hauv 500 mL dej, maj mam ntxiv 1.2 mol ntawm formaldehyde, thiab thaum kawg ntxiv 1 mol ntawm NaOH. Do thiab cua sov rau 90 degree thiab saib cov xim hloov ntawm cov qauv. Tom qab cov tshuaj tiv thaiv tiav lawm, cov reactant tau txias thiab lim, thiab tom qab ntawd cov tshuaj raug kho rau pH 6-7. Tom qab ntawd recrystallize nrog ethanol kom tau 3, 4-dihydroxyphenylethanol.
Kauj Ruam 2: Hloov 3, 4-dihydroxyphenylethanol rau Epinephrine Hydrochloride
Ua ntej, yaj 1mol ntawm 3,4-dihydroxyphenylethanol hauv 1000ml dej, thiab tom qab ntawd ntxiv NaOH cov nqi tsim nyog los ua kom alkaline. Tshav kub rau 60 degree thiab do, ces maj mam ntxiv qhov tsim nyog ntawm I2, thiab saib cov xim hloov ntawm cov tshuaj tiv thaiv thaum lub sij hawm cov tshuaj tiv thaiv. Thaum cov tshuaj tiv thaiv dhau lawm, nws yog rhuab mus rau 90 degree, thiab HCl yog ntxiv los kho nws rau acidity (pH≈4), thiab ces recrystallized nrog ethanol kom tau Epinephrine Hydrochloride.
Nyob rau lub sijhawm no, peb tau ua tiav kev npaj Epinephrine Hydrochloride. Kev ua kom huv, kev txiav txim siab ntawm nws lub cev thiab tshuaj lom neeg thiab kev sib piv nrog cov paub Epinephrine Hydrochloride tuaj yeem xyuas kom meej tias cov tshuaj npaj tau zoo raws li qhov yuav tsum tau ua.
3. 2, 5-Dihydroxybenzoic acid ester yog cov txheej txheem hluavtaws ntawm cov khoom siv raw:
Cov synthesis pib nrog 2, 5-dihydroxybenzoate thiab esterifies nws nrog Ac2O. Tom qab ntawd, nws tau hloov mus rau DL-epinephrine hydrochloride los ntawm ntau cov kauj ruam suav nrog hydroxyalkylation, deprotection, tautomerization, glutamination, thiab lwm yam. Txoj kev no muaj qee yam tawm los thiab purity.
Txoj kev npaj ntawm 2, 5-dihydroxybenzoate ntawm Epinephrine Hydrochloride feem ntau tuaj yeem muab faib ua cov kauj ruam hauv qab no:
3. 1. Esterify 2,5-dihydroxybenzoic acid nrog HCl kom tau 2,5-dihydroxybenzoic acid oxychloride.
3. 2. Cov tshuaj tiv thaiv ntawm 2, 5-dihydroxybenzoic acid hydroxychloride nrog CDI (1,1'-carbonyldiimidazole) hauv THF ua rau CDI-activated intermediate.
3. 3. React Epinephrine nrog CDI intermediate hauv THF los tsim 2, 5-dihydroxybenzoate.
3. 4. Kev ua kom huv ntawm 2, 5-dihydroxybenzoate tuaj yeem ua los ntawm recrystallization lossis kem chromatography.
Nws yuav tsum raug sau tseg tias kev xaiv cov tshuaj reagents, kev tswj hwm ntawm kev ua haujlwm thiab lwm yam ntsiab lus yuav cuam tshuam rau kev xaiv thiab tawm los ntawm cov tshuaj tiv thaiv, thiab kev npaj ntawm 2, 5-dihydroxybenzoate ntawm Epinephrine Hydrochloride yuav tsum tau ua tib zoo saib xyuas. xyuas kom cov yield thiab synthesis efficiency. Nyob rau tib lub sijhawm, kev ua haujlwm ntawm cov tshuaj tiv thaiv uas muaj cov tshuaj reagents muaj qee qhov kev pheej hmoo, thiab nws yuav tsum tau ua nyob rau hauv ib lub chaw soj nstuam, thiab cov kev ntsuas kev nyab xeeb tsim nyog yuav tsum tau them rau.
4. D, L-phenylalanine yog cov txheej txheem hluavtaws ntawm cov khoom siv raw:
Txoj hauv kev no yog ua raws li kev tshawb pom ntawm kev nplij siab ntawm D, L-phenylalanine residues los ntawm Fourier hloov pauv infrared spectroscopy thiab lwm yam kev ua qauv tsim qauv. Piv txwv li, ua ntej los ntawm esterifying D, L-phenylalanine rau cov methyl ester sib raug, thiab tom qab ntawd los ntawm kev txo qis thiab hydroxylation, 6-hydroxyadrenaline hloov mus rau hauv cov qauv ntawm DL-adrenaline. Txoj kev no muaj qhov zoo ntawm cov txiaj ntsig siab thiab siab purity.
Zuag qhia tag nrho, DL-epinephrine hydrochloride yog ib qho tseem ceeb heev uas siv dav hauv biomedical, kws tshuaj thiab tshuaj tshawb fawb. Ob peb txoj kev hluavtaws uas teev saum toj no yog txhua txoj hauv kev tseem ceeb tam sim no. Thaum xaiv ib txoj kev tshwj xeeb, cov yam ntxwv xws li tus nqi tsim nyog, cov khoom lag luam, lub sijhawm xav tau, thiab cov txheej txheem tshawb nrhiav yuav tsum tau txiav txim siab.