Uracilyog ib qho tseem ceeb pyrimidine derivative nrog ntau yam kev siv tshuaj lom neeg, kev kho mob thiab kev lag luam. Muaj ntau qhov kev tshawb fawb tau los ntawm kev sib txuas ntawm Uracil, suav nrog cov tshuaj synthesis, microbial synthesis thiab enzyme-catalyzed synthesis. Kab lus no yuav qhia txog ntau yam kev siv hluavtaws ntawm Uracil kom ntxaws.
1. Chemical synthesis:
Tshuaj synthesis yog ib qho ntawm thawj thiab feem ntau tus neeg sawv cev cov txheej txheem hluavtaws ntawm Uracil. Hauv kev sib xyaw tshuaj, Uracil tau txais los ntawm cov tshuaj tiv thaiv condensation ntawm 5-chlorouracil thiab acetylacetone, nrog rau kev hloov pauv tom qab los ntawm kev sib txawv. Ob peb classic tshuaj synthesis txoj hauv qab no:
1.1 Siv 5-chlorouracil raws li txoj kev hluavtaws ntawm cov khoom pib:
Txoj kev siv hluavtaws classic siv 5-chlorouracil ua cov khoom pib pib los ntawm kev tshawb fawb ntawm ob tus kws tshawb fawb, Cory thiab Shepherdson. Lawv synthesized Uracil los ntawm reacting 5-chlorouracil nrog pyridone los yog -ketoester. Tom qab ntawd, txoj kev hluavtaws no tau txhim kho thiab ua kom zoo dua los ntawm ntau tus kws tshawb fawb, cov npe nrov tshaj plaws suav nrog kev tshawb fawb ntawm Khorana thiab Dorfman li al.
Hauv xyoo 1950, pab pawg Khorana tau tsim Uracil siv 5-chlorouracil thiab acetylacetone ua cov khoom pib los ntawm plaub-kauj ruam cov tshuaj tiv thaiv. Ntawm lawv, cov tshuaj tiv thaiv condensation ntawm 5-chlorouracil thiab acetylacetone yog cov kauj ruam tseem ceeb kom tau txais cov precursor 5-chloro-2-formyl-4-carboxypyrimidine (CMCP) ntawm Uracil, ua raws li kev txo qis. , acid-catalyzed nplhaib scission thiab lub cev qhuav dej Uracil yog thaum kawg synthesized los ntawm ntau kauj ruam hloov dua siab tshiab nyob rau hauv cov tshuaj tiv thaiv.
Dorfman et al. txhim kho cov tshuaj synthesis ntawm 5-chlorouracil, siv sodium methyltrifluoromethanesulfonate (MeOTf) ua cov catalyst, thiab tau txais CMCP hauv cov tshuaj tiv thaiv condensation, thiab los ntawm kev sib xyaw ua ke ntawm condensation, decarboxylation thiab lwm yam tshuaj tiv thaiv Uracil thaum kawg tau tsim. Tom qab ntawd, qee qhov kev txhim kho ntawm txoj kev no suav nrog cov tshuaj tiv thaiv condensation ntawm pyridine nrog 2-oxourea, thiab kev siv 1, 3-dioxepane ua ib qho nruab nrab, thiab lwm yam.
1.2 Noj aminoketone raws li txoj kev hluavtaws ntawm cov khoom pib:
Ntxiv rau txoj kev siv hluavtaws siv 5-chlorouracil ua cov khoom pib, kuj tseem muaj txoj hauv kev siv aminoketone ua cov khoom pib. Nyob rau hauv txoj kev hluavtaws no, urease (Urease) yog siv los ua tus neeg sawv cev tsav tsheb rau hydrolyze uric acid rau diaminoacetic acid, thiab tom qab ntawd tau txais aminoketone nyob rau hauv alkaline tej yam kev mob. Tom qab oxidation ntawm aminoketone rau acyloxy pawg nyob rau hauv catalysis ntawm hydrogen iodide muab Uracil. Cov txheej txheem muaj siab atom kev lag luam thiab ib puag ncig tus phooj ywg, thiab yog ib txoj hauv kev sib xyaw ua ke nrog ntsuab chemistry.
2. Microbial synthesis:
Microbial synthesis yog hais txog kev sib txuas ntawm Uracil los ntawm microbial metabolic txoj hauv kev. Hauv qhov xwm txheej, Uracil yog cov metabolite tsim los ntawm eukaryotes thiab cov kab mob los ntawm cov metabolism ntawm deoxyribonucleic acid (DNA) thiab ribonucleic acid (RNA).
Hauv microbial synthesis, uric acid feem ntau yog siv los ua cov khoom pib, thiab Uracil yog thaum kawg synthesized los ntawm ntau theem metabolism. Piv txwv li no:
Hauv txoj kev no, uric acid yog decomposed rau hauv urea thiab pyruvate los ntawm catalysis ntawm ureidase; Tom qab ntawd, pyruvate hloov dua siab tshiab rau hauv uracil nrog kev koom tes ntawm ntau yam enzymes xws li carboxylase thiab carboxylation-decarbonylase, thiab tom qab Cov tshuaj tiv thaiv ntawm Uracil yog tau los ntawm pantothenic acid amide txoj kev. Cov txheej txheem enzymatic ntawm cov kab mob feem ntau los ua ke Uracil yog ze rau txoj kev metabolic ntawm pantothenic acid amide.
Tsis tas li ntawd, muaj cov ntaub ntawv tshaj tawm txog kev tsim cov kab mob engineering los ua ke Uracil los ntawm kev tsim cov noob caj noob ces, xws li kev siv hydroxybutyrate-3-carboxylate hydroxylase (HPCDH) uas tsim glycolic acid hauv Escherichia coli (E.coli) thiab dissociation. mus rau 9 Nrog kev koom tes ntawm enzymes xws li pyruvic acid decarboxylase (PDH-E2) ntawm lipoyl coenzyme A, biosynthesis ntawm Uracil hauv engineering kab mob tau pom thawj zaug siv succinic acid thiab amino compounds ua raw khoom.
3. Enzyme-catalyzed synthesis:
Enzyme-catalyzed synthesis txoj kev siv enzyme-catalyzed cov tshuaj tiv thaiv rau synthesize Uracil, uas muaj qhov zoo ntawm ib puag ncig tus phooj ywg thiab mob me me. Ntau cov enzymes tau pom los ua kom cov synthesis ntawm Uracil, feem ntau suav nrog: Uracil enzyme, urease thiab urease. Nov yog ob qho piv txwv:
3.1 Uracil enzyme-catalyzed synthesis:
Uracil enzyme tuaj yeem ua rau cov tshuaj tiv thaiv ntawm uracil thiab lwm cov tshuaj los ntawm -racemization isomerization kom tau Uracil. Ntawm lawv, uracil yog ib qho chaw uas muaj nyob rau hauv cov kab mob lom thiab muaj kev cia siab ntawm kev siv dav. Ob leeg Saccharomyces cerevisiae thiab Escherichia coli muaj Uracil enzyme, uas muaj ntau qhov chaw thov. Los ntawm kev sib txawv ntawm cov tshuaj tiv thaiv substrates, piv txwv li siv cov substrates sib txawv xws li lactate threonine thiab uracil, ob qho tib si kev ua tau zoo thiab cov khoom xa tawm tuaj yeem sib txawv.
3.2 Synthesis catalyzed los ntawm urease:
Txoj kev enzyme-catalyzed synthesis ntawm Uracil kuj suav nrog cov tshuaj tiv thaiv catalyzed ntawm urease. Urea yog ib qho enzyme uas tuaj yeem ua rau kev hloov pauv ntawm urea mus rau hauv urea thiab ammonia, uas urea tuaj yeem ua rau muaj kev cuam tshuam ntxiv los tsim Uracil. Los ntawm kev xaiv cov urea substrates sib txawv, xws li urea thiab phenylurea, thiab hloov cov catalytic tej yam kev mob ntawm cov tshuaj tiv thaiv, lub chaw soj nstuam-scale synthesis ntawm Uracil tuaj yeem ua tiav.
Hauv cov ntsiab lus, Uracil tuaj yeem raug tsim los ntawm ntau txoj hauv kev, suav nrog cov tshuaj sib xyaw ua ke, microbial synthesis, thiab enzyme-catalyzed synthesis. Cov txheej txheem hluavtaws no muaj cov ntawv thov dav dav hauv thaj chaw sib txawv, thiab tseem muab ntau yam kev xaiv rau kev tsim khoom loj ntawm Uracil.
Chemical Properties:
1. Keto-alcohol tautomerism: Hauv cov tshuaj aqueous, uracil thiab nws tautomer, hydrogen uracil, tau hloov mus rau ib leeg los ntawm kev cuam tshuam ntawm ib qho kev sib txawv proton.
2. N-glycosylation: Uracil tuaj yeem ua methyl-glycosylated los tsim 5-methyluracil.
3. Alkylation: Nyob rau hauv cov xwm txheej alkaline, uracil tuaj yeem ua alkylated, feem ntau yog siv cov tshuaj methylating tus neeg sawv cev methyl methyl carbonate.
4. Carboxymethylation: Cov pab pawg carboxyl tuaj yeem ua ke nrog uracil los ntawm carboxymethylation.
Reactive xwm:
1. Alkaline hydrolysis cov tshuaj tiv thaiv: Nyob rau hauv alkaline tej yam kev mob, uracil yuav hydrolyzed rau uracil acid, uas yog ib txoj kev ntawm DNA degradation.
2. Oxidation cov tshuaj tiv thaiv: Uracil tuaj yeem oxidized thiab hloov mus rau 5-hydroxyuracil, uas yog ib qho khoom tsim thaum lub sij hawm DNA puas.
3. Cov tshuaj tiv thaiv deamination: Uracil tuaj yeem tsim trihydrouracil los ntawm cov tshuaj tiv thaiv deamination.
4. Amination cov tshuaj tiv thaiv: Uracil tuaj yeem hloov mus rau hauv nruab nrab rau kev sib txuas ntawm acetaminobenzenesulfonic acid (ATPS) los ntawm ammoniation.
Uracil yog ib qho tseem ceeb ntawm cov organic molecule koom nrog ntau yam kev cuam tshuam hauv cell metabolism. Nws muaj ntau yam reactive zog, xws li ketol tautomerization, N-glycosylation, alkylation, carboxymethylation, thiab lwm yam. Tsis tas li ntawd, uracil tseem koom nrog qee qhov kev cuam tshuam tseem ceeb, xws li alkali hydrolysis, oxidation, deamination, ammoniation, thiab lwm yam. ib tug nplua nuj ntawm kev tshawb fawb thiab daim ntawv thov nqi. Piv txwv li, tshuaj lom neeg tuaj yeem ua ke los ntawm carboxymethylation, thiab alkaline hydrolysis ntawm uracil yog txoj hauv kev tseem ceeb rau DNA degradation. Cov kev tshawb fawb no ua rau peb nkag siab tob txog lub luag haujlwm thiab qhov tseem ceeb ntawm Uracil. kev pab tseem ceeb.