Thiostreptonndi mankhwala ovuta kwambiri a bakiteriya achilengedwe omwe amagwiritsidwa ntchito ngati topicalveterinarian antibiotickomanso ali ndi ntchito yabwino yoletsa malungo komanso anticancer.Panopa, izo kwathunthu mankhwala apanga.
Thiostrepton, yemwe adasiyanitsidwa koyamba ndi mabakiteriya mu 1955, ali ndi zochita zachilendo za maantibayotiki: amalepheretsa protein biosynthesis pomanga ku ribosomal RNA ndi mapuloteni ogwirizana nawo.Dorothy Crowfoot Hodgkin, wolemba makristalo waku Britain komanso wopambana Mphotho ya Nobel mu 1964, adapeza nyumbayi mu 1970.
Thiostrepton ili ndi mphete 10, zomangira 11 za peptide, unsaturation wambiri, ndi ma stereocenters 17.Chomwe chimakhala chovuta kwambiri ndichakuti chimakhudzidwa kwambiri ndi ma acid ndi maziko.Ndilo gulu la makolo komanso membala wovuta kwambiri wa gulu la maantibayotiki a thiopeptide.
Tsopano chigawo ichi chagonja ku kulankhula kokoma kwa pulofesa wa chemistry KS Nicolaou ndi anzake ochokera ku Scripps Research Institute ndi yunivesite ya California ku San Diego [Angew.Chemu.mayiko.Akonzi, 43, 5087 ndi 5092 (2004)].
Christopher J. Moody, Senior Research Fellow mu Dipatimenti ya Chemistry pa yunivesite ya Exeter, UK, anati: "Izi ndi zochitika zapadera komanso zomwe gulu la Nicolaou lachita modabwitsa."doxorubicin D.
Chinsinsi cha kapangidwe kaTHIOSTREPTONndi mphete ya dehydropiperidine, yomwe imathandizira mchira wa didehydroalanine ndi macrocycles awiri - mphete yokhala ndi thiazoline yokhala ndi 26 ndi 27-membered quinalcolic acid system.Nicolaou ndi anzake adapanga mphete ya dehydropiperidine kuchokera kuzinthu zosavuta zoyambira pogwiritsa ntchito biomimetic iso-Diels-Alder dimerization reaction.Gawo lofunikirali lidathandizira kutsimikizira lingaliro la 1978 loti mabakiteriya amagwiritsa ntchito izi popanga maantibayotiki a thiopeptide.
Nicolaou ndi anzake anaphatikiza dehydropiperidine mu macrocycle okhala ndi thiazoline.Iwo anaphatikiza macrocycle ndi kapangidwe munali quinalcolic acid ndi didehydroalanine mchira kalambulabwalo.Kenako anayeretsa katunduyo kuti apezethiostrepton.
Owunikanso mapepala awiri a gululo adati kaphatikizidweko "ndi mwaluso kwambiri womwe ukuwonetsa umisiri wamakono ndikutsegula njira zatsopano zopangira kafukufuku wofunikira pamapangidwe, zochita, ndi machitidwe."
Nthawi yotumiza: Oct-31-2023