5-Iodocytidineyog ib qho nucleotide molecule uas muaj iodine, uas yog dav siv nyob rau hauv biomedicine. Ob peb txoj kev hluavtaws ntawm 5-Iodocytidine yuav qhia hauv qab no.
(1) Pyrimidine txoj kev
Cov txheej txheem synthesis no ua ntej reacts pyrimidine nrog ozone kom tau txais 5-oxopyrimidine, ces reacts nws nrog methyl iodide kom tau txais 5-iodo-2'-deoxyuridine, thiab thaum kawg txo nws nrog 1,{{5 }}dichloro-2-propanol Cov tshuaj tiv thaiv yields 5-Iodocytidine. Cov khoom tsim los ntawm cov qauv no muaj purity siab, tab sis muaj ntau cov kauj ruam thiab cov kev xav tau ntawm cov tshuaj tiv thaiv yog qhov siab. Cov kauj ruam tshwj xeeb yog raws li hauv qab no:
Kauj Ruam 1: Npaj cov khoom siv raw uas xav tau
Ua ntej, cov khoom siv raw hauv qab no yuav tsum tau npaj:
- 5-aminoketose (5-amino-2,3,5-tri-O-acetyl- -D-ribofuranose)
- 5-iodouracil (5-iodouracil)
- Trichloroacetic acid
- Sodium hydroxide tov (NaOH)
- Hydrogen lossis hydrogen gas (H2)
- diphosphorus pentoxide
- Ethanol (ethanol)
- Dimethylacetamide (DMA)
Kauj Ruam 2: Kev npaj ntawm 5-Iodocytidine:
- Kauj Ruam 2.1
Cov 5-aminoketose thiab 5-iodouracil tau tshwm sim hauv cov tshuaj trichloroacetic acid nyob rau hauv chav tsev kub rau ob peb teev. Cov kauj ruam no yog kauj ruam tseem ceeb ntawm 5-Iodocytidine.
- Kauj Ruam 2.2
Ua kom cov reactants tso lawv los ntawm trichloroacetic acid. Cov tshuaj tiv thaiv sib tov tau ntxiv dropwise mus rau cov ntawv lim dej coated nrog pyrophosphoric anhydride. Cov khoom raug ntxuav hauv kev daws teeb meem ntawm sodium hydroxide, dej, ethanol thiab diacetamide. Tom qab ntxuav, cov khoom tau qhuav kom muab 5-iodocytidine.
Kauj Ruam 3: Xaus:
Txoj kev pyrimidine yog ib txoj hauv kev zoo rau kev npaj 5-Iodocytidine. Cov tshuaj tiv thaiv ntawm 5-aminoketose thiab 5-iodouracil hauv trichloroacetic acid ua rau kev npaj kawg ntawm 5-iodocytidine tom qab ob peb kauj ruam.
(2) Aldonic acid derivatization txoj kev:
Txoj kev ua ntej tau txais 5-chloro-2'-deoxyuridine los ntawm esterifying 5-chlorouridine nrog 3,4,6-tri-O-acetylgluconic acid, thiab tom qab ntawd ua cov tshuaj tiv thaiv iodination kom tau txais 5-iodo- 2'-Deoxyuridine. Thaum kawg, 5-Iodocytidine tau txais los ntawm kev txo cov tshuaj tiv thaiv. Cov txheej txheem muaj qhov zoo ntawm kev ua haujlwm yooj yim thiab cov khoom siab purity. Cov hauv qab no yog cov kauj ruam ntxaws:
1. Synthesis ntawm 5-hydroxymethyl-2'-deoxycytidine (5-HmdC): tshem tawm 2'-deoxycytidine hauv 1,4-dioxane, ntxiv acetyl chloride thiab aluminium trichloride, teb 5-Acetoxymethyl-2'-deoxycytidine yog tsim. Tom qab ntawd, 5-acetoxymethyl-2'-deoxycytidine tau yaj hauv methanol, thiab THF, dej, thiab NaBH4 tau ntxiv los tsim 5-HmdC.
2. Synthesis ntawm 5-Iodocytidine: Dissolve 5-HmdC nyob rau hauv hydrogen bromide thiab acetic acid, cua sov rau 6 teev los tsim 5-Iodocytidine.
3. Synthesis ntawm 5-Iodocytidine aldonic acid derivatives: Dissolve 5-Iodocytidine nyob rau hauv phosphate tsis. Ntxiv aldonic acid thiab teb rau 2 teev. Cov tshuaj tiv thaiv ces quenched nrog methyl formate thiab triethylsilyl chloride. Cov tshuaj tiv thaiv sib xyaw tau lim, thiab 5-Iodocytidine aldonic acid derivative tau los ntawm nag lossis daus.
4. Purification: Cov khoom tau txais yuav tsum tau ua kom huv, thiab kev ua haujlwm siab ua kua chromatography (HPLC) tuaj yeem siv rau kev sib cais thiab kev ua kom huv.
Cov saum toj no yog cov ncauj lus kom ntxaws cov kauj ruam ntawm 5-Iodocytidine aldonic acid derivatization txoj kev. Cov txheej txheem tuaj yeem siv los npaj cov khoom siv purity siab 5-Iodocytidine aldonic acid derivatives, thiab tuaj yeem ua tau raws li ntau yam kev xav tau hauv thaj chaw biomedicine thiab kev tshawb fawb tshuaj.
(3) Acid qab zib anhydride txoj kev:
Txoj kev no ua ntej reacts 2',3'-di-O-methyl glucoside nrog fumaric acid kom tau 2',3'-di-O-methyluridine ntsev, thiab tom qab ntawd hloov mus rau 5 '-Iodine-2', 3'-di-O-methyluridine ntsev, thiab thaum kawg 5-Iodocytidine tau los ntawm kev tshem tawm cov methyl pawg. Cov txheej txheem muaj cov tshuaj tiv thaiv me me thiab cov khoom siv purity siab, tab sis yuav tsum muaj cov khoom siv purity siab. Nws muaj qhov zoo ntawm kev ua haujlwm yooj yim thiab muaj txiaj ntsig siab. Cov nram qab no yog cov ncauj lus kom ntxaws synthetic cov kauj ruam.
1. Synthesis ntawm 5-iodo-2'-deoxycytidylate (CIDC ester)
(1) Dissolve 5-Iodocytidine (1.0g, 3.73mmol) nyob rau hauv 4 mL ntawm anhydrous triethylamine thiab txias rau 0 degree hauv da dej dej khov;
(2) Diethyl carbonate (0.70mL, 4.0mmol) tau ntxiv rau hauv cov tshuaj, thiab dimethylformamide (DMF) (0.50mL, 6.9mmol) tau maj mam ntxiv dropwise, thiab reacted rau 30 feeb;
(3) Ntxiv sodium hydroxide (0.50g, 12.5mmol) thiab stirring rau 30 feeb;
(4) Ntxiv acetonitrile (10mL), thiab cua nrog nitrogen cua rau 10 feeb;
(5) Ntxiv tetrabutylcopper(II) hydroxide (0.61g, 2.50mmol) thiab txuas ntxiv mus, thiab ua rau 1 teev;
(6) Ntxiv acetic anhydride (0.53mL, 5.0mmol), txuas ntxiv do, thiab teb rau 2 teev.
2. Synthesis ntawm 5-Iodocytidine
(1) Ntxiv dibutyl phosphate (2mL, 10.0mmol) rau cov tshuaj tiv thaiv txias thiab do rau 1 teev;
(2) Ntxiv chloroform (20mL), sib tov zoo, thiab ntxuav nrog dej;
(3) Sodium persulfate thiab silica gel kem uas cov organic theem yog qhuav yog ntxuav nyob rau hauv kem ntim rau hauv kem:
(4) Ua kom pom cov theem ntawm cov organic los ntawm kev tig mus rau hauv daim ntawv 5-iodocytidine.
Cov saum toj no yog txoj kev acid anhydrous ntawm 5-Iodocytidine thiab nws cov kauj ruam ntxaws. Thaum lub sij hawm txheej txheem synthesis, nws yog ib qho tsim nyog yuav tsum tau ua tib zoo saib xyuas kev nyab xeeb ntawm cov tshuaj lom neeg thiab cov cai tswj kev nyab xeeb ntawm chav kuaj. Thaum lub sijhawm ua haujlwm, peb yuav tsum ua raws li cov txheej txheem kev ua haujlwm raug cai, ntxiv dag zog rau kev paub txog kev nyab xeeb, ua haujlwm zoo hauv kev tiv thaiv kev nyab xeeb, thiab ua kom muaj kev nyab xeeb ntawm cov neeg ua haujlwm hauv chav kuaj.
(4) Txoj kev bromination:
Txoj kev no tau txais 5-bromouracil los ntawm reacting uracil nrog phosphorus tribromide, thiab tom qab ntawd nkag mus rau cov tshuaj tiv thaiv methylation kom tau txais 5-bromo-2'-deoxyuridine. Nws yog catalytically txo los ntawm kev siv sodium hydroxide thiab ammonium persulfate muab 5-Iodocytidine. Cov txheej txheem muaj tsawg dua cov kauj ruam, tab sis cov khoom muaj qis purity. Cov kauj ruam ntxaws yog raws li nram no:
1. Kev npaj ntawm tert-butyl isocyanate: Siv isocyanate, ntxiv acetone thiab triethylamine, tshuab nitrogen, thiab reflux rau 2 teev. Cov tshuaj tiv thaiv tau muab tso rau ntawm chav tsev kub. Lim lub precipitate kom tshem tawm cov ntsev inorganic thiab evaporate dua kom thaum kawg tau tert-butyl isocyanate
2. Hloov 5-chlorocytidine rau 5-iodocytidine: React 5-chlorocytidine, hydroiodic acid thiab acetic acid hauv methanol los hloov nws mus rau 5-iodocytidine. Tib lub sijhawm, iodide thiab cov poov tshuaj iodide ntau dhau kuj tuaj yeem siv los ua cov dej hauv dej, thaum cov nyiaj colloidal ntxiv los hloov 5-chlorocytidine rau 5-iodocytidine.
3. Ntxiv tert-butyl isocyanate rau 5-iodocytidine rau cov tshuaj tiv thaiv: Tom qab tau txais 5-iodocytidine, yaj nws hauv cov tshuaj sodium hydroxide, thiab ntxiv tert-butyl isocyanate. Lub sijhawm tshuaj tiv thaiv yog 2 teev ntawm chav tsev kub. Tom qab cov tshuaj tiv thaiv tiav, nws yog acidified nrog acetic acid, thiab cov khoom tshwm sim yog ntxiv rau bicarbonate diester rau extraction.
4. Purification ntawm 5-iodocytidine: Purify 5-iodocytidine kom tau cov khoom kawg 5-Iodocytidine.
Hauv luv luv, cov kauj ruam ntawm txoj kev bromination ntawm 5-Iodocytidine yog qhov nyuaj thiab yuav tsum tau ua kom zoo thiab xyaum ua tib zoo.
Hauv luv luv, muaj ntau txoj hauv kev los ua ke 5-Iodocytidine, thiab ntau txoj hauv kev tuaj yeem xaiv tau raws li qhov xav tau tiag tiag kom tau txais kev ua siab dawb huv 5-Iodocytidine.