Bremelanotide(link:https://www.bloomtechz.com/synthetic-chemical/peptide/bremelanotide-powder-cas-189691-06-3.html) yog ib qho hluavtaws polypeptide hormone uas nws cov qauv zoo ib yam li leptin, tyrosine thiab tawv nqaij melanin uas ib txwm muaj nyob hauv tib neeg lub cev. Raws li ib hom tshuaj tshiab, Bremelanotide muaj kev tswj hwm kev ua haujlwm thiab feem ntau siv rau hauv kev kho mob erectile kawg thiab qis libido. Kev siv cov xwm txheej hauv lub neej niaj hnub tau dhau los ua ntau dua. Nrog tib neeg txoj kev tshawb fawb tob rau nws, tib neeg tau tshawb pom ntau yam ntawm nws cov txheej txheem synthesis, uas yuav raug txheeb xyuas ib qho los ntawm ib qho hauv qab no.
1. Synthesized los ntawm L-tyrosine:
Nyob rau hauv thawj txheej txheem synthesis, tus qauv ntawm Bremelanotide tau los ntawm deforming L-tyrosine. Ua ntej, L-tyrosine hloov mus rau dipeptidyl-L-tyrosine (Boc-Tyr (OCO)2-OH) nyob rau hauv muaj hydrofluoric acid, qhov twg Boc sawv cev rau succinimidomethyl (t -butoxycarbonyl) pawg. Tom ntej no, ntxiv benzyl cawv (PhCH2OH), 1-(3-diethylaminopropoxy)-2-(2-methazolyl)ethane (EDC), thiab N-hydroxybutanediol hauv tetrahydrofuran (THF) Reagents xws li imide (HOBt) tuaj yeem sib xyaw dipeptidyl-L-tyrosine nrog pseudopeptide alanine (Phe-Aib-Aib-Lys(Ac)-Gly-Lys(Ac)-Aib-Leu- NH2) tau tsim los rau hauv Bremelanotide.
(1) Kev hloov pauv ntawm L-tyrosine rau dipeptidyl-L-tyrosine:
Ua ntej, yaj L-tyrosine hauv dej thiab ntxiv cov nqi tsim nyog ntawm hydrofluoric acid. Feem ntau, qhov concentration ntawm L-tyrosine yog 1M thiab tus nqi ntawm hydrofluoric acid yog 5-10%. Cov sib tov tau tso cai sawv ntawm 0-4 degree rau 1 teev thiab tom qab ntawd quenched.
Tom qab ntawd, cov tau txais L-tyrosine-hydrofluoric acid complex tau ntxiv dropwise rau tetrahydrofuran. Nyob rau tib lub sijhawm, qhov tsim nyog cov tshuaj tiv thaiv cov tshuaj tiv thaiv xws li benzyl cawv, EDC thiab HOBt tau ntxiv rau tetrahydrofuran. Tom qab sawv ntsug li 2 teev hauv qab nplawm, dipeptidyl-L-tyrosine (Boc-Tyr(OCO)2-OH) tuaj yeem tau.
(2) Cov tshuaj tiv thaiv dipeptidyl-L-tyrosine nrog pseudopeptide alanine:
Dissolve cov tau dipeptidyl-L-tyrosine hauv N, N-dimethylformamide (DMF) thiab ntxiv pseudopeptide alanine. Cov tshuaj tiv thaiv muaj xws li kub, lub sij hawm tshuaj tiv thaiv, thiab concentration ntawm reactants, thiab lwm yam. Cov yam tseem ceeb no yuav cuam tshuam rau cov txiaj ntsig thiab purity ntawm cov khoom. Ntawm qhov concentration ntawm 225 g / L, qhov piv ntawm Boc-Tyr (OCO) 2-OH rau pseudopeptide alanine yog 1:30.
Tom qab nplawm thiab sawv hauv -N, N-dimethylformamide rau 24 teev, cov tshuaj tiv thaiv yog nchuav rau hauv dej khov dej thiab precipitated nrog acidic aldehyde tov. Qhov tshwm sim yog cov khoom kawg ntawm Bremelanotide.
Cov txheej txheem synthesis feem ntau muaj qhov zoo hauv qab no: cov khoom lag luam siab purity thiab cov txheej txheem tsim khoom yooj yim. Tab sis txoj kev no kuj muaj qee qhov tsis zoo, xws li siv sijhawm ntev, tus nqi siab thiab lwm yam.
2. Khoom theem synthesis:
Solid-theem synthesis yog tam sim no ib qho ntawm feem ntau siv hluavtaws txoj kev rau Bremelanotide, thiab nws kuj yog ib tug tseem ceeb hluavtaws txoj kev nyob rau hauv lub teb ntawm peptide synthesis. Hauv cov txheej txheem txheej txheem, polypeptide chains yog tsim los ntawm kev sib ntxiv ntawm cov amino acid units. Ua ntej, thawj cov amino acid chav tsev tau hloov kho rau hauv ib qho kev txwv tsis pub muaj kev txwv thiab tsis-degradable N-tiv thaiv pab pawg (xws li Fmoc), uas tom qab ntawd txuas mus rau qhov nruab nrab porous. Tom ntej no, los ntawm kev qhia cov pab pawg neeg tiv thaiv acrylic acid, acylation cov tshuaj tiv thaiv thiab lwm cov kauj ruam, txhua chav amino acid ntxiv rau ntawm qhov ntxeem tau nruab nrab, thiab cov saw hlau ua tiav polypeptide yog maj mam tsim. Thaum kawg, nyob rau hauv cov kauj ruam ntawm kev tshem tawm N-tiv thaiv pab pawg neeg, denitrification, thiab lwm yam, ib tug Bremelanotide polypeptide saw nrog ib tug tshwj xeeb ib theem zuj zus tuaj yeem npaj tau.
Cov txheej txheem sib xyaw ua ke feem ntau muaj qhov zoo hauv qab no: kev ua haujlwm siab thiab kev siv siab ntawm cov khoom siv raw. Tab sis cov txheej txheem hluavtaws no kuj muaj qee qhov tsis zoo, xws li ntau yam ziab thiab ntxuav cov kauj ruam yuav tsum tau ua hauv cov txheej txheem tsim khoom, thiab cov kauj ruam no yuav ua rau cov khoom tsis zoo.
3. Ua kua theem synthesis:
Ua kua theem synthesis yog lwm txoj kev synthesis ntawm Bremelanotide, uas yog ua los ntawm cov kua tshuaj tiv thaiv kab mob. Cov kauj ruam tseem ceeb ntawm cov txheej txheem synthesis suav nrog kev tshuaj xyuas cov khoom siv raw, kev tsim tshuaj molecule, kev xaiv txoj kev sib txuas, cov tshuaj tiv thaiv, purification thiab lwm yam. Piv nrog rau cov khoom siv-theem synthesis, cov txheej txheem ua kua-theem synthesis tuaj yeem tau txais Bremelanotide nrog ntau dua purity thiab lom lom. Nyob rau hauv txoj kev ua kua theem synthesis, feem ntau siv cov tshuaj tiv thaiv reagents yog dihydroxyethyl mercaptan (EDT), ethoxycarbonylating agent (EEDQ), thioacetyl chloride, thiab lwm yam.
Txoj kev ua kua theem synthesis feem ntau muaj qhov zoo hauv qab no: kev ua haujlwm yooj yim thiab cov khoom siab purity. Txawm li cas los xij, txoj kev sib xyaw no kuj muaj qee qhov tsis zoo, xws li lub sijhawm sib xyaw ua ke ntev dua thiab tus nqi siab dua.
4. Physicochemical synthesis:
Nyob rau hauv txoj kev physicochemical synthesis, Bremelanotide yog synthesized los ntawm lub cev thiab tshuaj txoj kev. Txoj kev no feem ntau muaj ob txoj hauv kev sib txawv: ib qho yog kom paub txog kev sib txuas ntawm Bremelanotide los ntawm kev rov ua haujlwm ntawm cov khoom ua kua theem hloov pauv; lwm qhov yog los txhawb kev sib dhos ntawm tus kheej thiab polymerization ntawm polypeptide chains los ntawm kev siv lub cev thiab cov neeg kho tshuab compression, yog li synthesizing Bremelanotide.
Cov tshuaj tiv thaiv mechanism:
Lub synthesis ntawm Bremelanotide yog tsuas yog los ntawm kev hloov L-tyrosine rau hauv L-phenolic acylate, ces synthesizing L-phenolic acylate thiab pseudopeptide, thiab thaum kawg tau txais cov khoom. Lub mechanism ntawm cov tshuaj tiv thaiv yog raws li nram no:
(1) Kev hloov pauv ntawm L-tyrosine rau L-phenol acylate:
L-tyrosine reacts nrog sodium azide hauv THF tov los tsim L-phenol acylate. Sodium azide yuav hloov cov pab pawg hydroxyl hauv tyrosine mus rau ib pawg azide, thiab tom qab ntawd kev kho acidic yuav hloov cov pab pawg azide mus rau phenolic acylate.
(2) L-phenol acylate hloov mus rau hauv acid chloride:
L-phenolic acylate reacts nrog acetyl chloride hauv THF los tsim cov kua qaub chloride. Tsib zaug tus nqi ntawm TBHS yog nqus cov HCl generated. Acid chlorides yog cov tshuaj tiv thaiv intermediates uas yuav tsum tau rau cov kev tshwm sim tom ntej.
(3) Synthesis ntawm acid chloride thiab pseudopeptide:
Qhov nruab nrab acid chloride reacts nrog pseudopeptide hauv DMF los tsim cov polypeptide saw ntawm Bremelanotide. Dab tsi tshwm sim hauv cov kauj ruam no yog cov tshuaj tiv thaiv anhydride condensation, uas HOBt yog cov catalyst.
(4) Purification thiab tsom xam ntawm cov khoom:
Cov khoom kawg tseem yuav tsum tau ua kom huv thiab tshuaj xyuas kom ntseeg tau tias qhov purity thiab zoo ntawm cov compound.
Cov txheej txheem physicochemical synthesis feem ntau muaj qhov zoo hauv qab no: kev ua haujlwm yooj yim thiab lub sijhawm npaj luv. Txawm li cas los xij, txoj kev siv hluavtaws no kuj muaj qee qhov tsis zoo, xws li cov khoom siv purity tsawg thiab tsis txaus cov khoom sib txawv.
Nyob rau hauv xaus, cov synthesis txoj kev ntawm Bremelanotide muaj ntau haiv neeg thiab saj zawg zog, thiab cov kev xaiv nyob ntawm ntau yam, xws li cov tshuaj tiv thaiv tej yam kev mob, synthesis nqi thiab cov tshuaj tiv thaiv lub sij hawm, thiab lwm yam. Txawm li cas los xij ntawm txoj kev siv, ruaj khov tshuaj tiv thaiv tej yam kev mob thiab high-purity khoom yog cov. yuam sij rau kev vam meej synthesis ntawm Bremelanotide.