Thiostreptonchigadzirwa chebhakitiriya chakaoma kunzwisisa chinoshandiswa semushonga wekurapamushonga unorwisa utachiona wemhukauye ine simba rakanaka rekurwisa malaria uye kenza. Parizvino, yakagadzirwa nemakemikari zvakakwana.
Thiostrepton, yakatanga kutorwa kubva kumabhakitiriya muna 1955, ine basa risingawanzoitwa remaantibiotic: inodzivirira kugadzirwa kwemapuroteni nekusungana neribosomal RNA nemapuroteni akabatana nayo. Dorothy Crowfoot Hodgkin, nyanzvi yekuongorora makristalo yekuBritain uye akahwina mubairo weNobel Prize muna 1964, akawana chimiro ichi muna 1970.
Thiostrepton ine rings gumi, 11 peptide bonds, extensive unsaturation, uye stereocenters gumi nenomwe. Chinonyanya kuoma ndechekuti inobatwa zvakanyanya neacids nemabases. Ndiyo mubereki uye ndiyo nhengo yakaoma kwazvo yemhuri ye thiopeptide antibiotics.
Iye zvino mushonga uyu wakundwa nepfungwa dzechinyakare dzepurofesa wekemesitiri KS Nicolaou nevamwe vake vekuScripps Research Institute neYunivhesiti yeCalifornia kuSan Diego [Angew. Chem. internationality. Editors, 43, 5087 na5092 (2004)].
Christopher J. Moody, Senior Research Fellow muDhipatimendi reChemistry paYunivhesiti yeExeter, UK, akati: “Uku kuumbwa kwakakosha uye kubudirira kunoshamisa kweboka raNicolaou.” doxorubicin D.
Kiyi yechimiro cheTHIOSTREPTONndiyo mhete ye dehydropiperidine, inotsigira muswe we didehydroalanine uye macrocycles maviri - mhete ine thiazoline ine nhengo 26 uye system ye quinalcolic acid ine nhengo 27. Nicolaou nevamwe vake vakagadzira mhete yakakosha ye dehydropiperidine kubva pazvinhu zviri nyore zvekutanga vachishandisa biomimetic iso-Diels-Alder dimerization reaction. Danho iri rakakosha rakabatsira kusimbisa chikumbiro cha1978 chekuti mabhakitiriya ashandise reaction iyi ku biosynthesize thiopeptide antibiotics.
Nicolaou nevamwe vake vakasanganisa dehydropiperidine mu macrocycle ine thiazoline. Vakasanganisa macrocycle iyi nechimiro chine quinalcolic acid uye didehydroalanine tail precursor. Vakazochenesa chigadzirwa ichi kuti chiwanethiostrepton.
Vaongorori vemapepa maviri eboka iri vakati kubatanidzwa uku "ibasa guru rinoratidza matekinoroji emazuva ano uye rinovhura nzira itsva dzekutsvaga zvine musoro muchimiro, chiitiko, uye maitiro ekuita."
Nguva yekutumira: Gumiguru-31-2023