18 -Glycyrrhetinic Acid(18 -Glycyrrhizic acid) yog lub ntuj triterpenoid feem ntau pom nyob rau hauv cov hauv paus hniav thiab rhizome ntawm Glycyrrhiza. Nws yog xim dawb rau lub teeb daj crystalline hmoov uas tsis muaj ntxhiab tsw thiab qab zib. 18 -Glycyrrhetinic Acid muaj ntau yam tshuaj ua haujlwm, suav nrog tshuaj tiv thaiv kab mob, tiv thaiv oxidation, tiv thaiv kab mob, tiv thaiv qog, hypolipidemic, hypoglycemic, thiab hepatoprotective teebmeem.
Nyob rau hauv xyoo tas los no, 18 -Glycyrrhetinic Acid kuj tau siv dav hauv cov tshuaj pleev ib ce thiab cov khoom kho mob rau daim tawv nqaij moisturizing, whitening, anti-aging thiab lwm yam. Tib lub sijhawm, qee qhov kev tshawb fawb tau pom tias 18 -Glycyrrhetinic Acid kuj tuaj yeem siv los ua cov neeg nqa tshuaj lossis pab pawg hloov kho, uas muaj peev xwm txhim kho cov tshuaj bioavailability thiab xaiv. Yog li ntawd, ntau tus kws tshawb fawb tau sim ntau txoj hauv kev ntau zaus los txhim kho nws cov purity. Cov hauv qab no yog cov kev siv tshuaj synthesis ntau dua:
method ib:
1>, synthesis ntawm 3-hydroxy-11-methyl-δ-lactic acid
3-Hydroxy-11-methyl-δ-lactic acid tuaj yeem tau los ntawm hydroxylation thiab methylation ntawm 2-methylglutaric acid. Cov kauj ruam tshwj xeeb yog:
(1) Ntxiv 2-methylglutaric acid rau acetonitrile, thiab ntxiv cov catalysts xws li H2O2 thiab NaOH los tsim 3-hydroxy-2-methylglutaric acid.
(2) Ntxiv 3-hydroxy-2-methylglutaric acid rau methyl iodide, thiab ntxiv cov catalysts xws li potassium carbonate los tsim 3-hydroxy-11-methyl-δ-lactic acid.
2>Synthesis ntawm 18 -glycyrrhizic acid
(1) React 3-hydroxy-11-methyl-δ-lactic acid nrog methacrylate nyob rau hauv lub xub ntiag ntawm ib tug esterifying agent (xws li DCC los yog EDC) los tsim 3-hydroxy-11- methyl-δ-lactic acid Methacrylate.
(2) 3-Hydroxy-11-methyl-δ-lactate methyl acrylate yog hydrolyzed los tsim 18 -glycyrrhizic acid.
3>Kev ua kom huv ntawm 18 -glycyrrhizic acid
Tom qab tau txais 18 -glycyrrhizic acid, yuav tsum tau ua kom huv ntxiv thiab crystallization, thiab cov tswv yim xws li recrystallization lossis chromatography tuaj yeem siv rau kev ua kom huv.
Txoj Kev Ob:
Cov kauj ruam ntxaws ntxaws ntawm cov txheej txheem hluavtaws pib los ntawm acetylacetone:
(1) Thaum tshav kub kub acetylacetone thiab butanone oxide ime (3-butanone alumina) hauv chloroform los tsim 1,3-dibutyl-2,4-cyclohexanedione.
(2) Thaum tshav kub kub 1, 3-dibutyl-2, 4-cyclohexanedione thiab formaldehyde hauv acetic acid los tsim 3-methoxy-1, 5-hexanedione.
(3) React 3-methoxy-1, 5-hexanedione thiab isobutyl magnesium kua hauv tetrahydrofuran los tsim 4-isobutoxy-3-methoxy-1, {{ 7}} hexanetrione.
(4) React 4-isobutoxy-3-methoxy-1, 5-hexanetrione thiab potassium hydroxide hauv tetrahydrofuran los tsim 4-isobutoxy-3-hydroxy{{7 }}, 5- hexane Triketones.
(5) React 4-isobutoxy-3-hydroxy-1, 5-hexanetrione thiab chloromethyl acetone hauv chloroform los tsim 4-isobutoxy-3-hydroxy{{7 }}, 5-hexanetrione Ketone-11-methanone.
(6) React 4-isobutoxy-3-hydroxy-1, 5-hexanetrione-11-methanone thiab potassium hydroxide hauv ethanol los tsim 18 -hydroxymethyl{{7 }}keto-olean- 12-en{10}}oic acid.
Txoj kev peb:
Cov hauv qab no yog cov txheej txheem synthesis ntawm 18 -Glycyrrhetinic Acid pib los ntawm potassium bicarbonate:
(1) Oxidation: Cua sov acetylacetone thiab chromium acidate ua ke rau oxidation cov tshuaj tiv thaiv kom tau txais 3-hydroxypentanone.
(2) Cov tshuaj tiv thaiv Carbonylation: react 3-hydroxypentanone thiab formaldehyde nyob rau hauv alkaline tej yam kev mob rau carbonylation cov tshuaj tiv thaiv kom tau txais 3-hydroxy-5-methoxypentanone.
(3) Oxidative acylation: Cua sov 3-hydroxy-5-methoxypentanone thiab hydrogen chloride ua ke rau cov tshuaj tiv thaiv chlorination kom tau txais 3-chloro-5-methoxypentanone. Tom qab ntawd hnov mob 3-chloro-5-methoxypentanone thiab potassium bicarbonate hauv acetone rau oxidative acylation kom tau txais 18 -Glycyrrhetinic Acid.
Tag nrho cov kev sib npaug sib npaug yog raws li hauv qab no:
3-Hydroxypentanone ntxiv rau CrO3/Hntxiv→ 3-Hydroxy-5-methoxypentanone
3-Hydroxy-5-methoxypentanone plus HCHO/NaOH → 3-hydroxy-5-methoxypentanone
3-Hydroxy-5-methoxypentanone ntxiv HCl → 3-chloro-5-methoxypentanone
3-Chloro-5-methoxypentanone plus KHCO3→ 18 -Glycyrrhetinic Acid
Txoj kev plaub:
Cov hauv qab no yog cov txheej txheem synthesis ntawm 18 -Glycyrrhetinic Acid pib los ntawm -maltose:
(1) Dissolution: Dissolve -maltose hauv dej, ntxiv sodium hydroxide thiab styrene, thiab do zoo.
(2) Oxidation: ntxiv hydrogen peroxide los ua cov tshuaj tiv thaiv oxidation kom tau 3,20-dihydroxy-11-keto-olean-12-ene.
(3) Chlorination: Cua sov 3,20-dihydroxy-11-keto-olean-12-ene thiab hydrogen chloride ua ke rau cov tshuaj chlorination kom tau txais 3-chloro-11-keto- olean-12-ib.
(4) Carboxylation: react 3-chloro-11-keto-olean-12-ene nrog hydrogen chloride nyob rau hauv muaj sodium chloride rau carboxylation kom tau 3-chloro-11- carboxy-olean-12-ene .
(5) Hydroxylation: Cua sov 3-chloro-11-carboxy-olean-12-ene thiab sodium carbonate ua ke rau hydroxylation cov tshuaj tiv thaiv kom tau txais 18 -Glycyrrhetinic Acid.
Tag nrho cov kev sib npaug sib npaug yog raws li hauv qab no:
-maltose plus NaOH plus C6H5CH =CH2→ 3,20-dihydroxy-11-keto-olean-12-ene
3,20-dihydroxy-11-keto-olean-12-ene plus H2O2→ 3,20-dihydroxy-11-keto-olean-12-ene
3,20-dihydroxy-11-keto-olean-12-ene plus HCl → 3-chloro-11-keto-olean-12-ene
3-chloro-11-keto-olean-12-ene plus HCl plus NaCl → 3-chloro-11-carboxy-olean-12-ene
3-Chloro-11-carboxy-olean-12-ene plus Na2CO3→ 18 -Glycyrrhetinic Acid
Txoj kev 5:
Cov hauv qab no yog cov txheej txheem synthesis ntawm 18 -Glycyrrhetinic Acid pib los ntawm steroid nucleus:
(1) Dissolution: Dissolve lub steroid nucleus hauv acetic acid, ntxiv ib qho acidulant, thiab do zoo.
(2) Chlorination: ntxiv ferrous chloride lossis aluminium trichloride los ua cov tshuaj tiv thaiv chlorination kom tau chlorinated steroids.
(3) Carboxylation: Cua sov chlorinated steroids thiab sodium hydroxide ua ke rau carboxylation cov tshuaj tiv thaiv kom tau carboxylic acid steroids.
(4) Hydroxylation: Cua sov carboxylic acid steroids thiab sodium hydroxide ua ke rau hydroxylation cov tshuaj tiv thaiv kom tau txais 18 -Glycyrrhetinic Acid.
Tag nrho cov kev sib npaug sib npaug yog raws li hauv qab no:
Steroid Core ntxiv rau CH3COOH ntxiv rau Acidulant → Chlorinated Steroid
Chlorinated Steroids ntxiv rau FeCl2/AlCl3→ Chlorinated Steroids
Chlorinated Steroid plus NaOH → Carboxylic Steroid
Carboxylic acid steroid plus NaOH → 18 -Glycyrrhetinic Acid
Cov saum toj no yog ntau txoj hauv kev hauv chav kuaj, rau kev siv nkaus xwb, thiab hauv qhov kev sim tshwj xeeb, koj yuav tsum xaiv cov kev sib txawv raws li koj tus kheej qhov kev sim.