Thiostreptonchinhu chakaomesesa chakanyanya kuomesesa chebhakitiriya chigadzirwa chinoshandiswa semusoroveterinary antibioticuye zvakare ine yakanaka antimalarial uye anticancer chiitiko.Parizvino, yakanyatsogadzirwa nemakemikari.
Thiostrepton, yakatanga kuparadzaniswa kubva kubhakitiriya muna 1955, ine basa remishonga inorwisa mabhakitiriya isina kujairika: inodzivirira mapuroteni biosynthesis nekusunga kune ribosomal RNA nemapuroteni ayo anobatanidzwa.Dorothy Crowfoot Hodgkin, British crystallographer uye 1964 Nobel Prize akawana chimiro muna 1970.
Thiostrepton ine zvindori gumi, 11 peptide bond, yakakura unsaturation, uye 17 stereocenters.Zvakatonyanya kunetsa inyaya yekuti inonyatsonzwa kune acids uye mabhesi.Ndiyo musanganiswa wevabereki uye nhengo yakaoma kwazvo yemhuri yetiopeptide inorwisa mabhakitiriya.
Ikozvino komisheni iyi yakakundwa nekutaura kunotapira kwemakemikari purofesa KS Nicolaou nevamwe vake kubva kuScripps Research Institute uye University of California kuSan Diego [Angew.Chem.internationality.Vapepeti, 43, 5087 uye 5092 (2004)].
Christopher J. Moody, Senior Research Fellow muDhipatimendi reChemistry paYunivhesiti yeExeter, UK, akati: “Uku kuumbwa kwakakosha uye kubudirira kunoshamisa kweboka reNicolaou.”doxorubicin D.
Kiyi kune chimiro cheTHIOSTREPTONndiyo mhete ye dehydropiperidine, inotsigira didehydroalanine muswe uye macrocycles maviri - 26-membered thiazoline-containing ring uye 27-membered quinalcolic acid system.Nicolaou nevamwe vaaishanda navo vakagadzira kiyi dehydropiperidine mhete kubva kuzvinhu zviri nyore zvekutanga vachishandisa biomimetic iso-Diels-Alder dimerization reaction.Iyi nhanho yakakosha yakabatsira kusimbisa chirevo cha1978 chekuti mabhakitiriya ashandise kuita uku kubiosynthesize thiopeptide mishonga inorwisa mabhakitiriya.
Nicolaou nevamwe vaaishanda navo vakasanganisa dehydropiperidine mune thiazoline-ine macrocycle.Vakabatanidza iyi macrocycle nechimiro chine quinalcolic acid uye didehydroalanine muswe precursor.Vakabva vachenesa chigadzirwa kuti vawanethiostrepton.
Vaongorori vemapepa maviri eboka vakati mubatanidzwa uyu "inyanzvi inoburitsa matekinoroji echizvino-zvino uye inovhura horizons nyowani dzetsvakiridzo ine musoro muchimiro, chiitiko, uye maitiro."
Nguva yekutumira: Oct-31-2023