I-Tautomer-Defined Pyridinone Scaffold Yezivimbamgciwane Ze-p38 Kinase, I-Favipiravir Analog Synthesis, Kanye Nama-Biomass-Derived Nitrogen Heterocycles: 6-Methylpyridine-2,4-diol CAS# 3749-51-7

6-Methylpyridine-2,4-diol (CAS# 3749-51-7), eyaziwa nangokuthi i-4-hydroxy-6-methyl-2(1H)-pyridinone, i-4-hydroxy-6-methyl-1H-pyridin-2-one, i-2,4-dihydroxy-6-methylpyridine, i-4,6-dihydroxy-2-picoline, noma i-NSC 110283, iyinhlanganisela ye-hydroxypyridinone heterocyclic enefomula yamangqamuzana i-C₆H₇NO₂ kanye nesisindo samangqamuzana esingu-125.13 g/mol. Isakhiwo sayo samangqamuzana sinesiyingi se-pyridine esinezinhlangano ze-hydroxyl ezindaweni zesi-2 nesi-4 kanye neqembu le-methyl endaweni yesi-6—iphethini yokufaka eshintshayo enquma uhlobo lwayo oluyinhloko lwe-tautomeric njenge-4-hydroxy-6-methyl-2(1H)-pyridinone. Inhlanganisela ivela njengempushana ekhazimulayo e-beige kuya kunsundu ngokukhanyayo noma empunga enephuzu lokuncibilika lika-324–330°C, ukuzinza okuhle kakhulu kokushisa (>320°C), i-pKa ebikezelwe engaba ngu-4.50, kanye ne-UV λmax engu-282 nm ku-ethanol. Itholakala ngokuthengisa ngezinga lokuhlanzeka okungu-≥97–98% (HPLC/GC) futhi kufanele igcinwe ekamelweni lokushisa esitsheni esomile nesivalwe kahle.

Isici esichazayo se-6-methylpyridine-2,4-diol ukuthambekela kwayo okuqondile kwe-tautomeric kokwakheka kwe-4-hydroxy-2-pyridinone. Lokhu kuhlelwa okukhethekile kwe-elekthroniki ne-steric—ama-hydroxyl ezindaweni zika-2,4 kanye neqembu le-methyl endaweni yesi-6—kubalulekile endimeni yayo njenge-intermediate eqondene ne-isomer ekuhlanganiseni ama-molecule e-bioactive afana nama-p38 kinase inhibitors. Ukufaka esikhundleni i-isomer eseduze efana ne-2,6-dihydroxy-4-methylpyridine kungashintsha ngokuyisisekelo i-regiochemistry yokusabela okulandelayo, okungaholela kuphrofayela yomkhiqizo ehlukile futhi kungenzeka kuqede umsebenzi we-biological ofunwayo. Lokhu kukhethwa kwe-regioselectivity echazwe yi-tautomer, kuhlangene nokuzinza okukhulu kwe-thermal okwenza izinyathelo zokwenziwa kwe-synthetic ezingeni lokushisa eliphezulu ezingenakwenzeka ngama-isomer ane-melting ephansi, kubeka i-6-methylpyridine-2,4-diol njenge-building block ebalulekile ngokwesu ku-medicinal chemistry yesimanje, ukuthuthukiswa kwe-pharmaceutical, kanye nokuhlanganiswa kwe-biomass-derived nitrogen heterocycle.

Isidingo semakethe se-6-methylpyridine-2,4-diol (CAS# 3749-51-7) sigxile emikhakheni emine eyinhloko: ucwaningo nokuthuthukiswa kwemithi kanye nokwenziwa kwe-p38 kinase inhibitor (cishe u-40–45% wokusetshenziswa komhlaba wonke), ukuthuthukiswa kwe-antimicrobial ne-antifungal analog (cishe u-20–25%), ukwenziwa kwe-biomass-derived nitrogen heterocycle (cishe u-15–20%), kanye nezilinganiso zereferensi zokuhlaziya kanye nezicelo zamakhemikhali akhethekile (cishe u-10–15%). I-regioselectivity echazwa yi-tautomer kanye nokuzinza kwayo okuphezulu kwe-thermal kuyizinto eziyinhloko ezishayela ukukhula kwesidingo okuqhubekayo.

Ekuthuthukisweni kwemithi kanye nasekwenziweni kwe-p38 kinase inhibitor, i-6-methylpyridine-2,4-diol iyisisekelo esibalulekile sokwenziwa kwe-p38 kinase inhibitors—iqembu lamakhemikhali aphenywayo ukwelapha izifo zokuvuvukala. I-p38 mitogen-activated protein kinases iyisisekelo ekwakhiweni kwama-cytokine avusa ukuvuvukala njenge-TNF-α ne-IL-1β, okwenza ukuvinjelwa kwazo kube yisu eliqinisekisiwe le-rheumatoid arthritis, i-psoriasis, nezinye izimo zokuvuvukala. Ukuthambekela okucacile kwe-tautomeric kwale nhlanganisela ohlotsheni lwe-4-hydroxy-2-pyridinone kuqinisekisa ukusebenza kwe-regioselective kuma-cyclocondensation nama-cross-coupling reactions, okuvumela ukwenziwa okuphindaphindekayo kwezinto eziphakathi ze-p38 inhibitor. Le nhlanganisela isebenza njengesakhi esibalulekile sokwakha imitapo yolwazi yokutholakala kwemithi esekelwe ku-pyridinone, isekela imikhankaso ye-hit-to-lead kanye ne-lead optimization eqondiswe ezindleleni zokuvuvukala.

Ekuthuthukisweni kwama-analog e-antimicrobial kanye ne-antifungal, i-6-methylpyridine-2,4-diol isetshenziselwa ukwakha ama-analog e-Favipiravir (T-705), umuthi we-antiviral we-prodrug obanzi osebenza ngempumelelo kuma-RNA virus afaka i-influenza, ama-arenavirus, kanye ne-SARS-CoV-2. Isakhiwo se-pyridinone se-6-methylpyridine-2,4-diol sivumela ukwakhiwa kwama-analog e-Favipiravir anezici eziguquliwe ze-pharmacokinetic kanye ne-antiviral, okusekela ukuthuthukiswa kwemithi ye-antiviral yesizukulwane esilandelayo. Izinto ezisuselwa kule nhlanganisela zibuye zibonise imisebenzi ye-antimicrobial kanye ne-fungicidal, okuyenza ibaluleke ekuthuthukiseni izinto ezintsha ezilwa nezifo.

Ekukhiqizeni i-nitrogen heterocycle etholakala kwi-biomass, i-6-methylpyridine-2,4-diol isebenza njengesixhumanisi esiyisisekelo sokukhiqiza i-2-methylpiperidine evuselelekayo (76.5% yokukhiqiza) kanye ne-6-methylpiperidin-2-one (78.5% yokukhiqiza). Lawa ma-nitrogen heterocycle atholakala kwi-biomass amelela izindlela ezisimeme ezishintsha izinto zokuxhuma ze-petrochemical ekukhiqizeni imithi, ama-agrochemical, kanye namakhemikhali akhethekile. Le nhlanganisela iphinde isetshenziswe ekwakheni i-4-pyridinyl-4H-chromenes yemitapo yokuthola ama-hit-to-lead, ethola ukukhiqiza okungu-82–99% kuma-domino synthesis emizuzu emi-5. Ama-iron(III) complexes ayo aziwa kahle—[Fe(4H6M2P)₃(SCN)₃]—ayacwaningwa ngezinhlelo zokusebenzisa i-antimicrobial coordination chemistry.

Kumasilinganiso okubhekisela kwezokuhlaziya kanye nasekusetshenzisweni kwamakhemikhali akhethekile, i-6-methylpyridine-2,4-diol ifaneleka njengento yokubhekisela ekuthuthukisweni kwezindlela zokuhlaziya, ukulinganisa, nokulawulwa kwekhwalithi. Isetshenziswa njengesakhi esimsulwa kakhulu ekuhlanganiseni izinto eziphilayo nasekuthuthukisweni komkhiqizo kuzo zonke izindawo zocwaningo nezimboni, futhi isetshenziswa njenge-ligand kukhemistri yokuxhumanisa kanye ne-catalysis.

I-6-Methylpyridine-2,4-diol (CAS# 3749-51-7) iyi-hydroxypyridinone echazwe nge-tautomer okubaluleka kwayo kuvela ekusabeleni okuhlukile kwe-2-pyridone carbonyl yayo, i-4-hydroxyl, kanye ne-6-methyl substituents.

Amapharamitha ayisisekelo e-physicochemical ahlanganisa:

I-compound reactivity ichazwa ama-handle ayo akhethekile e-tautomer: i-2-pyridone carbonyl inikeza indawo yokwengezwa kwe-nucleophilic, i-condensation, kanye nokuxhumana ne-metal; iqembu le-4-hydroxyl livumela i-etherification, i-esterification, kanye ne-hydrogen bonding; futhi iqembu le-6-methyl lilawula izici ze-electronic zeringi futhi linikeza ukulawula kwe-steric phezu kwe-reaction regioselectivity. Ukukhethwa okucacisiwe kwe-tautomeric kwefomu le-4-hydroxy-2-pyridinone kuqinisekisa i-reactivity ebikezelwayo kuma-cyclocondensation ne-cross-coupling reactions—isidingo esibalulekile sokwenziwa kabusha kwe-bioactive molecules. I-compound yakha ama-metal complexes azinzile ngokuxhumana kwe-bidentate okubandakanya i-pyridone carbonyl kanye neqembu le-hydroxyl eliseduze.

Uhlelo lokuhlinzeka lomhlaba wonke lwe-6-methylpyridine-2,4-diol (CAS# 3749-51-7) lunephathini yabakhiqizi abakhethekile bezakhi zama-heterocyclic, abasabalalisi bamakhemikhali ocwaningo bamazwe ngamazwe, kanye nabakhiqizi baseShayina abasebenza ezigabeni zemakethe ezihlukene. Njengoba iyisisekelo se-pyridinone esichazwe nge-tautomer esikhethekile hhayi impahla yobuningi, imakethe ibonakala ngenani elilinganiselwe labahlinzeki abasebenzala ucwaningo lwezidakamizwa, i-medicinal chemistry, kanye nocwaningo lwezemfundo.

Ezingxenyeni zocwaningo lomhlaba wonke kanye nezinga lokuhlanzeka okuphezulu, abahlinzeki abakhulu bamazwe ngamazwe bahlanganisa i-Fluorochem (UK), enikeza le nhlanganisela nge-95% yokuhlanzeka ngaphansi kwekhodi yomkhiqizo F068449, etholakala e-UK, eJalimane naseChina. I-AK Scientific (AKSci) inikeza le nhlanganisela nge-98% (HPLC) yokuhlanzeka ngaphansi kwekhodi yomkhiqizo Y8909, ene-5 g, 25 g, kanye ne-100 g EKHONA ESITOKWENI evela e-SF Bay Area, eCalifornia. I-Thermo Fisher Scientific (Acros Organics) inikeza le nhlanganisela nge-97% yokuhlanzeka (96% ubuncane nge-HPLC) ngaphansi kwenombolo yekhathalogi i-AAA15439-06 kanye ne--14, enemininingwane ehlanganisa ukubukeka kwempushana ensundu ngokukhanyayo. I-Tokyo Chemical Industry (TCI) inikeza le nhlanganisela nge->98.0% (GC)(T) yokuhlanzeka ngaphansi kwekhodi yomkhiqizo D4361. I-Apollo Scientific (UK) inikeza le nhlanganisela nge-98% yokuhlanzeka nge-HPLC ngaphansi kwenombolo yekhathalogi i-AS476241, enokubukeka okuqinile okumpunga kuya kokunsundu ngokukhanyayo kanye nokuqinisekiswa kwe-1H-NMR. I-Combi-Blocks inikeza le nhlanganisela ngaphansi kwekhodi yomkhiqizo SS-6632 ngokugcinwa ezingeni lokushisa legumbi. I-BOC Sciences inikeza le nhlanganisela ngaphansi kwenombolo yekhathalogi 3749-51-7 njenge-4-hydroxy-6-methyl-2-pyridinone. I-CymitQuimica inikeza le nhlanganisela nge-98% yokuhlanzeka nge-HPLC enokubukeka okuqinile okumpunga kuya kokunsundu ngokukhanyayo. I-VWR International inikeza le nhlanganisela nge-97% yokuhlanzeka enemininingwane ye-HPLC ≥96.0%. Laba bahlinzeki bakhonza imiphakathi yezemithi, ubuchwepheshe bezinto eziphilayo, kanye nocwaningo lwezemfundo ngemikhiqizo ehlangabezana nezimfuneko eziqinile zekhwalithi.

Ezingxenyeni zezimboni kanye nokukhiqizwa okukhulu, i-XinChem ingumkhiqizi nomhlinzeki othembekile we-6-methylpyridine-2,4-diol yekhwalithi ephezulu evela e-China, enikeza le nhlanganisela ngamazinga ekhwalithi aqinile ukuze isetshenziswe ekuhlanganiseni kwe-p38 kinase inhibitor, ukuthuthukiswa kwe-Favipiravir analog, kanye nokukhiqizwa kwe-biomass-derived nitrogen heterocycle. I-XinChem inikeza le nhlanganisela njengempushana ekhazimulayo e-beige kuya kokunsundu ngokukhanyayo enemibhalo yekhwalithi ephelele, izitifiketi ze-Analysis (COA) eziqondene neqembu ezihlanganisa idatha ye-HPLC ne-1H-NMR, ukupakishwa okungaguquguquka, kanye nokukhiqizwa okuhambisana ne-REACH, ISO 9001, kanye ne-GMP emhlabeni wonke. Inkampani igcizelela ukuthi i-6-methylpyridine-2,4-diol iyisakhi esibalulekile esinokuthanda okuchaziwe kwe-tautomeric okubalulekile ekuhlanganiseni kwe-regioselective, esebenza njengento yokuqala ebalulekile yama-p38 kinase inhibitors kanye nama-Favipiravir analogs. Abanye abahlinzeki esifundeni banikeza le nhlanganisela ngamazinga ahlukene ekhwalithi (ngokuvamile 95–99%) kanye nezinketho zokupakisha—kusuka ku-250 mg kuya ku-2.5 kg—bakhonza izimakethe zasekhaya nezokuthumela ngaphandle.

Imakethe yomhlaba wonke ye-6-methylpyridine-2,4-diol ibonisa izici zesifunda ezihlukile, ngokukhiqiza okugxile e-Asia-Pacific (ikakhulukazi eShayina) nokusetshenziswa okusatshalaliswa eNyakatho Melika, eYurophu, nasezifundeni zase-Asia-Pacific, okuhambisana nezimboni zezidakamizwa, i-biotechnology, kanye nocwaningo lwezemfundo kulezi zifunda.

Isifunda sase-Asia-Pacific sesivele saba yisizinda esibalulekile sokukhiqiza i-6-methylpyridine-2,4-diol, kanti i-China inabakhiqizi nabahlinzeki abaningi abafaka phakathi i-XinChem. Izinzuzo zokuncintisana zalesi sifunda zifaka izindleko eziphansi zokukhiqiza, ingqalasizinda yamakhemikhali eseyakhiwe, kanye nokuba seduze nezimboni zomuthi ne-biotechnology ezikhula ngokushesha. Abahlinzeki kulesi sifunda banikeza le nhlanganisela ngamazinga ahlukene okuhlanzeka (ngokuvamile angu-95–99%) kanye nezinketho zokupakisha, basebenzele izimakethe zasekhaya nezokuthumela kwamanye amazwe. Imikhakha ekhulayo yocwaningo nokuthuthukiswa kwezomuthi, ukuthuthukiswa kwe-p38 kinase inhibitor, kanye nokutholakala kwezidakamizwa ezilwa namagciwane e-China, e-India, e-Japan nase-South Korea iyaqhubeka nokuqhuba ukukhula kokusetshenziswa kwesifunda. Le nhlanganisela ihlukaniswa njenge-pharmaceutical intermediate kanye nesakhi se-fine chemical building block emakethe yaseChina, kanti abahlinzeki abaningi banikeza lo mkhiqizo ngosayizi wokupakisha osukela ku-250 mg kuya ku-2.5 kg.

INorth America ihlala iyimakethe ebalulekile ye-high-purity kanye ne-research-grade 6-methylpyridine-2,4-diol, eqhutshwa yisidingo esivela embonini yezemithi, izinkampani ze-biotechnology, kanye nezikhungo zocwaningo zemfundo. I-United States inezingi izinhlangano zocwaningo, izinkampani zemithi, kanye nezinhlangano zocwaningo ezisebenza ngemvumelwano ezidinga ama-tautomer-defined pyridinone scaffolds asezingeni eliphezulu ukuze kutholakale i-p38 kinase inhibitor, ukuthuthukiswa kwe-Favipiravir analog, kanye nokuhlanganiswa kwe-biomass-derived heterocycle. I-AK Scientific, i-Thermo Fisher Scientific, i-BOC Sciences, kanye nabanye abasabalalisi bamazwe ngamazwe basebenzela imakethe yaseNyakatho Melika ngamanethiwekhi okusabalalisa abanzi. Uhlaka lwemithetho olusungulwe kahle lwalesi sifunda, okuhlanganisa nokuqondisa kwe-FDA kucwaningo nokuthuthukiswa kwemithi, lusekela isidingo samakhemikhali ocwaningo asezingeni eliphezulu kanye nama-pharmaceutical intermediates.

IYurophu ibonakala ngezimfuneko eziqinile zokulawula, kuhlanganise nokubhaliswa kwe-REACH, kanye nokugxila okunamandla ekhwalithini nasekusimameni ocwaningweni lwemithi namakhemikhali. Izinkampani zemithi zaseYurophu, amalabhorethri ekhemistri yemithi, kanye nezikhungo zocwaningo zidinga izingqamuzana eziyingqayizivele ze-heterocyclic ezinobumsulwa obuphezulu ezinemibhalo ephelele. I-Fluorochem (UK), i-Thermo Fisher Scientific (Acros Organics), kanye ne-Apollo Scientific (UK) zisebenzela imakethe yaseYurophu ngokutholakala kwesitoko. Inhlanganisela ibhaliswe ngaphansi kwe-REACH ngenombolo ye-EINECS 690-441-0. Imikhakha eqinile yemithi ne-biotechnology yalesi sifunda isekela isidingo esingaguquki sezinto eziphuma ku-pyridinone zekhwalithi ephezulu.

I-Japani imelela imakethe ekhethekile lapho i-6-methylpyridine-2,4-diol ihlinzekwa yi-Tokyo Chemical Industry (TCI) kanye nabanye abasabalalisi ukuze kusetshenziselwe ucwaningo lwemithi, ukuthuthukiswa kwe-kinase inhibitor, kanye nezicelo zamakhemikhali acolekile.

Njengengxenye yokwakha ye-hydroxypyridinone heterocyclic kanye ne-pharmaceutical intermediate, i-6-methylpyridine-2,4-diol (CAS# 3749-51-7) ingaphansi kokugadwa komthetho emazweni amakhulu omhlaba. Ukuhambisana nemithetho efanele kubalulekile ukuze kufinyelelwe emakethe nokuhweba.

I-6-Methylpyridine-2,4-diol ihlukaniswa negama lesignali elithi "Isexwayiso". Izitatimende zengozi zihlanganisa i-H315 (Idala ukucasuka kwesikhumba), i-H319 (Idala ukucasuka okukhulu kwamehlo), kanye ne-H335 (Ingase idale ukucasuka kokuphefumula). Ikhompawundi ihlukaniswa njenge-Skin Irrit. 2, Eye Irrit. 2, kanye ne-STOT SE 3 (uhlelo lokuphefumula). Imisho yokuphepha ihlanganisa i-P261 (Gwema ukuphefumula uthuli/intuthu/igesi/umusi/umhwamuko/isifutho), i-P264 (Geza izandla ngokuphelele ngemuva kokuphatha), i-P270 (Ungadli, unganathi futhi ungabhemi lapho usebenzisa lo mkhiqizo), i-P271 (Sebenzisa ngaphandle kuphela noma endaweni enomoya ohamba kahle), kanye ne-P280 (Gqoka amagilavu okuzivikela/izingubo zokuzivikela kanye nokuvikela amehlo/ubuso). Ikhompawundi ihlukaniswa njenge-GHS07 – Eyingozi/Edala ukucasuka. Izinto zokuzivikela komuntu siqu ezihlanganisa amagilavu aselebhu, izibuko zokuphepha, kanye nejakethe yaselebhu kufanele zigqokwe ngesikhathi sokuphatha, futhi imisebenzi kufanele yenziwe endaweni enomoya ohamba kahle noma ku-fume hood. Ikhompawundi iyiqinile ekamelweni lokushisa futhi kufanele iphathwe ngokucophelela ukuze kugwenywe ukukhiqizwa kothuli.

I-6-Methylpyridine-2,4-diol kufanele igcinwe ezingeni lokushisa legumbi esitsheni esivalwe ngokuqinile esivikelwe emswakameni naselangeni. Inhlanganisela ibonisa ukuzinza okuhle kakhulu kokushisa (>320°C) futhi izinzile ngaphansi kwezimo zokugcina ezinconywayo. Kufanele igcinwe kude neziqhumisi ezinamandla.

E-European Union, i-compound kufanele ihambisane nezidingo zokubhaliswa kwe-REACH zokungeniswa nokusetshenziswa. I-compound inenombolo ye-EINECS engu-690-441-0 kanye nenombolo ye-MDL engu-MFCD01860849. Abakhiqizi nabahlinzeki kufanele banikeze ama-Safety Data Sheets (SDS) aphelele futhi bagcine imibhalo efanele. E-United States, i-6-methylpyridine-2,4-diol ihloselwe ukusetshenziswa ocwaningweni nasekuthuthukisweni kuphela futhi ayihloselwe ukwelashwa, ukudla, izimonyo, noma ukusetshenziswa kwabathengi ngaphandle uma kushiwo ngokusobala ngenye indlela. Ezinhlelweni zokusetshenziswa kwe-pharmaceutical intermediate, abakhiqizi kufanele bahambisane nemithetho efanele ye-FDA kanye namazinga ekhwalithi. I-compound ayisona isidakamizwa esilawulwayo.

I-6-Methylpyridine-2,4-diol ayihlukaniswa njengento eyingozi ngezinjongo zokuthutha ze-DOT/IATA ngaphansi kwezimo ezijwayelekile. Ukupakishwa okufanele, ukulebula, kanye nemibhalo kuyadingeka ekuthumeleni kwamazwe ngamazwe. Inhlanganisela ivamise ukuthunyelwa ngezinga lokushisa elijwayelekile ngokuvikelwa okufanele emswakameni nasekukhanyeni.

Umbono wemakethe we-6-methylpyridine-2,4-diol muhle, usekelwa izinto ezimbalwa ezibalulekile zokukhula kuzo zonke izigaba zokusetshenziswa kwawo ezinkulu. Nakuba le nhlanganisela iseyisisekelo se-pyridinone esichazwe nge-tautomer esisetshenziswa kakhulu, indima yayo ebalulekile ekuthuthukisweni kwe-p38 kinase inhibitor kanye ne-Favipiravir analog, kuhlangene nokusetshenziswa kwayo ekuhlanganiseni i-biomass-derived nitrogen heterocycle, kuyibeka endaweni yokukhula okungaguquki eminyakeni ezayo.

Izinto ezibalulekile zokukhula zihlanganisa:

Ukuthuthukiswa okuqhubekayo kwama-p38 kinase inhibitors ezifo zokuvuvukala—kufaka phakathi i-rheumatoid arthritis, i-psoriasis, ne-chronic obstructive pulmonary disease—kuholela ekudingekeni kwama-tautomer-defined pyridinone scaffolds aqinisekisa ukuhlanganiswa kwe-regioselective. Ukukhethwa kwe-tautomeric okuchaziwe kwalesi sakhi kokuthanda ifomu le-4-hydroxy-2-pyridinone kubalulekile ekuhlanganisweni okuphindaphindekayo kwama-p38 inhibitor intermediates, okusekela isidingo esiqhubekayo ezinhlelweni zokutholakala kwezidakamizwa zokuvuvukala.

Ukugxila komhlaba wonke okukhulayo ekutholakaleni kwezidakamizwa ezilwa namagciwane, ikakhulukazi kumagciwane e-RNA afaka i-influenza, ama-arenavirus, ne-SARS-CoV-2, kushukumisa isidingo se-6-methylpyridine-2,4-diol njengento yokuqala ebalulekile yokwenziwa kwe-Favipiravir analog. Isakhiwo se-pyridinone sale nhlanganisela sivumela ukwakhiwa kwama-analog e-Favipiravir ashintshiwe anezici ezingcono ze-pharmacokinetic kanye nezilwa namagciwane.

Ukugcizelelwa okukhulayo kwezinto ezivuselelwayo kanye nekhemistri esimeme kuqhuba isidingo se-6-methylpyridine-2,4-diol njenge-gateway intermediate yokukhiqizwa kwe-2-methylpiperidine evuselelwayo (76.5% yield) kanye ne-6-methylpiperidin-2-one (78.5% yield). Lezi zinto eziphilayo ezisuselwa ku-biomass zimelela izindlela ezisimeme zokushintsha izinto zokwenziwa kwe-petrochemical ekukhiqizeni imithi kanye namakhemikhali akhethekile.

Ukwanda kokuqashelwa kwendima ebalulekile yokukhethwa kwe-tautomeric ekunqumeni i-regioselectivity yokusabela kanye nomsebenzi wezinto eziphilayo kushayela isidingo se-6-methylpyridine-2,4-diol njenge-building block echazwe nge-tautomer engenakushintshwa ama-isomer asondelene nawo ngaphandle kokwethula ubungozi obulinganisekayo ku-regiochemistry kanye namaphrofayili omkhiqizo.

Ama-complex e-iron(III) ale khompiyutha achazwe kahle—[Fe(4H6M2P)₃(SCN)₃]—ayacwaningwa ukusetshenziswa kukhemistri yokuxhumanisa ye-antimicrobial, okusekela isidingo esivela emalabhorethri ocwaningo ezemfundo nezimboni.

Izinselelo kanye nokucatshangelwa:

Njenge-scaffold ye-pyridinone echazwe nge-tautomer ekhethekile, imakethe ye-6-methylpyridine-2,4-diol incane kunaleyo yamakhemikhali ajwayelekile.

Imakethe ibhekene nokuncintisana okuvela kwezinye izinto ezisuselwa ku-hydroxypyridinone kanye nezingqamuzana ze-heterocyclic ezinamaphrofayili okusabela afanayo. Ukufaka esikhundleni i-isomer eseduze efana ne-2,6-dihydroxy-4-methylpyridine kungashintsha ngokuyisisekelo i-regiochemistry yokusabela okulandelayo.

Ukuhlukaniswa kwale nhlanganisela njengesicasuli (H315, H319, H335) kudinga izinyathelo zokuphepha ezifanele ngesikhathi sokuphatha nokugcina.

Imithetho eqinisa kakhulu yezemithi neyamakhemikhali ingase idinge ukutshalwa kwezimali okuqhubekayo ezinhlelweni zekhwalithi kanye nemibhalo.

Ukuze uphumelele kulesi simo semakethe esiguqukayo, abahlinzeki kufanele bagxile ekhwalithini yomkhiqizo (ikakhulukazi ukungaguquguquki kwe-tautomer kanye nokuphindaphindeka kwe-batch-to-batch), ukuthembeka kwe-supply chain, ukuhambisana nemithetho, kanye nesevisi yamakhasimende esabelayo. Izinkampani ezinganikeza imikhiqizo yokuhlanzeka okuphezulu enezitifiketi eziphelele zokuhlaziya (COA) ezihlanganisa idatha ye-HPLC ne-1H-NMR, izinketho zokupakisha eziguquguqukayo, kanye nokusekelwa kobuchwepheshe kwezicelo zemithi, i-medicinal chemistry, kanye ne-biomass-derived heterocycle zizoba sesimweni esihle sokuthatha isidingo esikhulayo.

IShanghai XinChem Co., Ltd. (XinChem) ingumhlinzeki ohamba phambili emhlabeni wamakhemikhali e-organic kanye nezingqamuzana ze-heterocyclic building blocks. Inkampani izinikele ekuhlangabezaneni nezidingo ezintsha zezimboni zemithi, i-biotechnology, kanye namakhemikhali acolekile. Ngokusebenzisa ulwazi olubanzi kanye namakhono okukhiqiza athuthukile, i-XinChem ihlinzeka nge-6-Methylpyridine-2,4-diol (CAS# 3749-51-7) yekhwalithi ephezulu kumakhasimende emhlabeni wonke.

Njengomkhiqizi nomhlinzeki othembekile ozinze e-China, i-XinChem ihlanganisa amanani ancintisanayo, ukuhlinzeka okuthembekile, kanye nesevisi ekhethekile ukuze izimise njengomlingani okhethwayo wezinkampani zemithi, abacwaningi bemithi yamakhemikhali, kanye nezikhungo zokuthola imithi ezifuna lesi sakhiwo se-pyridinone esiguquguqukayo esichazwe nge-tautomer.

I-XinChem isebenzisa izikhungo zokukhiqiza ezisezingeni eliphezulu kanye nezinyathelo zokuqapha izinga eziqinile ukuze iqinisekise ukuhlanzeka, ukungaguquguquki, kanye nokuthembeka kwe-tautomer yemikhiqizo yayo ye-6-methylpyridine-2,4-diol. Inqubo yokukhiqiza ihlanganisa izindlela zokwenziwa ezisunguliwe—kuhlanganise nokuhlakazwa kwe-dehydroacetic acid ibe yi-4-hydroxy-6-methyl-2H-pyran-2-one okulandelwa ukufakwa kwe-ammonia ukuze kukhiqizwe i-4-hydroxy-6-methyl-2-pyridinone—okuvumela ukulethwa kwemikhiqizo enokuhlanzeka okungu-≥97% (HPLC/GC) kanye no-≥98% (HPLC/GC) ukuze kuhlangatshezwane nezidingo ezahlukene zokusetshenziswa. Ukulawulwa kwenqubo okuqinile kuqinisekisa izinga lomkhiqizo elingaguquguquki, ukukhethwa kwe-tautomeric okuchaziwe (ifomu le-4-hydroxy-2-pyridinone), ukungcola okuncane, kanye nokuphindaphindeka kobungako bemikhiqizo ngemikhiqizo, okunikeza amakhasimende ukusebenza okuthembekile ekwenziweni kwe-p38 kinase inhibitor, ukuthuthukiswa kwe-Favipiravir analog, kanye nokukhiqizwa kwe-biomass-derived nitrogen heterocycle.

Inqubo yokukhiqiza ilandela ngokuqinile izindinganiso zamazwe ngamazwe zekhwalithi, ngokulawulwa kwekwalithi okuphelele okuhlanganisa ukutholakala kwezinto zokusetshenziswa, ukuqapha phakathi nenqubo, nokuhlolwa komkhiqizo ophelile. I-batch ngayinye ihambisana ne-Certificate of Analysis (COA) enemininingwane ebhala izici zomzimba namakhemikhali, idatha yokuhlanzeka (HPLC/GC), ukubukeka, ukuqinisekiswa kobunikazi nge-1H-NMR, kanye namaphrofayili okungcola. I-XinChem inikeza i-COA eqondene ne-batch, ukupakisha okungashintshwa, kanye nokukhiqiza okuhambisana ne-REACH, ISO 9001, kanye ne-GMP emhlabeni wonke.

I-XinChem inikeza i-6-methylpyridine-2,4-diol enobumsulwa obungu-≥97% (HPLC/GC) kanye no-≥98% (HPLC/GC) etholakalayo, eqinisekisa ukusebenza okuphezulu ekuhlanganiseni i-p38 kinase inhibitor, ukuthuthukiswa kwe-Favipiravir analog, kanye nokukhiqizwa kwe-biomass-derived nitrogen heterocycle. Ukuthanda kwe-tautomeric okuchaziwe komkhiqizo kwefomu le-4-hydroxy-2-pyridinone kuqinisekisa imiphumela yokuhlanganisa i-regioselective, okuyenza ifanelekele izinhlelo ezidinga kakhulu ekutholakaleni kwezidakamizwa kanye nekhemistri yemithi. Le nhlanganisela inikezwa njengempushana e-crystalline enombala osuka ku-beige kuya ku-pale brown enokubukeka okungaguquki kanye nokucaciswa kwe-melting point echaziwe (324–330°C).

Izincazelo ezibalulekile zifaka:

I-XinChem inikeza izinhlobo ezahlukene zezinketho zokupakisha ukuze kuhlangatshezwane nezidingo zamakhasimende ahlukahlukene, kusukela kumanani esikali saselabhorethri (1 g, 5 g, 25 g) kuya ekupakisheni kwesikali sezimboni (100 g, 500 g, 1 kg, 2.5 kg) kanye nokuthunyelwa okukhulu. Izixazululo zokupakisha ezenziwe ngokwezifiso ziyatholakala uma ziceliwe, ziqinisekisa ukuphathwa okuphephile, ukugcinwa, kanye nokuthutha ngokuvikelwa okufanele emswakameni nasekukhanyeni.

Njenge-pyridinone scaffold echazwe nge-tautomer, i-6-Methylpyridine-2,4-diol (CAS# 3749-51-7) ibonisa inani elibanzi lokusetshenziswa ezimbonini eziningi:

Ithimba lika-XinChem losokhemisi abanolwazi kanye nonjiniyela bezinhlelo luhlinzeka ngosekelo oluphelele lwezobuchwepheshe phakathi nohambo lwamakhasimende—kusukela ekukhetheni umkhiqizo nasekuthuthukiseni imininingwane kuya ekuqondiseni ngokusetshenziswa nasekuxazululeni izinkinga. Kungakhathaliseki ukuthi amakhasimende adinga ukuthuthukiswa kwezimo ze-cyclocondensation, isiqondiso mayelana nokusabela okuhlukile kwe-tautomer, noma usizo ngezincwadi zokulawula, ochwepheshe bezobuchwepheshe bakwa-XinChem bakulungele ukusiza. Ukuhlanganiswa okwenziwa ngokwezifiso kanye nokukhiqizwa ngenkontileka okunokukhula okuguquguqukayo kusuka ocwaningweni nasekuthuthukisweni kuya kumanani okuhweba kuyatholakala uma kuceliwe.

Ngamaketanga okuhlinzeka asunguliwe asebenzela izimakethe kulo lonke elaseYurophu, eNyakatho Melika, e-Asia-Pacific, nangale kwayo, i-XinChem iqinisekisa ukulethwa ngesikhathi nokutholakala komkhiqizo okungaguquguquki. Ithimba lezokuthutha lale nkampani liphethe zonke izici zokuthunyelwa kwamazwe ngamazwe, okuhlanganisa ukugunyazwa kwempahla kanye namadokhumenti, ngokuvikelwa okufanele ekumswakameni nasekukhanyeni ukuze kugcinwe ukuzinza komkhiqizo.

I-XinChem inikeza imibhalo ephelele yokweseka ukuhambisana nemithetho, okuhlanganisa ama-Safety Data Sheets (SDS), ama-Certificates of Analysis (COA), nezinye izitifiketi ezidingekayo. Inkampani ihlala ihambisana nezidingo zemithetho eziguqukayo ezimakethe ezinkulu, okuhlanganisa i-REACH, i-TSCA, neminye imithetho yesifunda, isiza amakhasimende ukuba abhekane nobunkimbinkimbi bokuhweba komhlaba wonke.

Isipiliyoni esibanzi nobuchwepheshe obujulile ekuhlanganiseni nasekuphakeleni kwezingxenye zokwakha ze-heterocyclic.

Ukulawulwa kwekhwalithi okuqinile, ukuhlanzeka okuphezulu (≥97% kuya ku-≥98%), ukungaguquguquki kwe-tautomer, nokuhambisana nezindinganiso zamazwe ngamazwe.

Ukuhlinzeka okuzinzile, amanani ancintisanayo, nokulethwa ngesikhathi.

Izixazululo ezenzelwe umuntu ngamunye ukuhlangabezana nezidingo ezahlukene zamakhasimende, kufaka phakathi ukuhlanganiswa okwenziwe ngokwezifiso nokupakishwa.

Ukusekelwa kobuchwepheshe okusabelayo kanye nemibhalo ephelele kufaka phakathi i-COA eqondene neqembu.

Xhumana nathi namuhla ukuze uqale ubudlelwano bakho ne-XinChem!

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