Kupeza ndi Kukula kwa Thiostrepton

       Thiostreptonndi mankhwala ovuta kwambiri achilengedwe a bakiteriya omwe amagwiritsidwa ntchito ngati mankhwala opaka pakhungumankhwala opha tizilombo toyambitsa matenda a ziwetondipo ili ndi mphamvu zabwino zothana ndi malungo komanso khansa. Pakadali pano, imapangidwa ndi mankhwala okhaokha.
Thiostrepton, yomwe idatulutsidwa koyamba ku mabakiteriya mu 1955, ili ndi ntchito yodabwitsa yolimbana ndi maantibayotiki: imaletsa kupanga mapuloteni mwa kumamatira ku ribosomal RNA ndi mapuloteni ogwirizana nayo. Dorothy Crowfoot Hodgkin, katswiri wa makristalo waku Britain komanso wopambana mphoto ya Nobel mu 1964, adapeza kapangidwe kake mu 1970.
Thiostrepton ili ndi mphete 10, ma peptide bond 11, kusakwanira kwakukulu, ndi stereocenters 17. Chovuta kwambiri ndichakuti imakhudzidwa kwambiri ndi ma acid ndi ma bases. Ndi chinthu chachikulu komanso chovuta kwambiri m'gulu la ma antibiotic a thiopeptide.
Tsopano mankhwalawa agwera m'nkhani yokoma yopangidwa ndi pulofesa wa chemistry KS Nicolaou ndi anzake ochokera ku Scripps Research Institute ndi University of California ku San Diego [Angew. Chem. internationality. Editors, 43, 5087 ndi 5092 (2004)].
Christopher J. Moody, Mkulu Wofufuza mu Dipatimenti ya Chemistry ku University of Exeter, UK, anati: “Iyi ndi njira yodziwika bwino yopangira zinthu komanso kupambana kwakukulu kwa gulu la Nicolaou.” doxorubicin D.
Chinsinsi cha kapangidwe kaTHIOSTREPTONNdi mphete ya dehydropiperidine, yomwe imathandizira mchira wa didehydroalanine ndi ma macrocycles awiri - mphete yokhala ndi thiazoline yokhala ndi ziwalo 26 ndi dongosolo la quinalcolic acid yokhala ndi ziwalo 27. Nicolaou ndi anzake adapanga mphete yofunika kwambiri ya dehydropiperidine kuchokera kuzinthu zosavuta zoyambira pogwiritsa ntchito biomimetic iso-Diels-Alder dimerization reaction. Gawo lofunikali linathandiza kutsimikizira lingaliro la 1978 lakuti mabakiteriya agwiritse ntchito izi popangira maantibayotiki a thiopeptide.
Nicolaou ndi anzake adaphatikiza dehydropiperidine mu macrocycle yokhala ndi thiazoline. Adaphatikiza macrocycle iyi ndi kapangidwe kake kokhala ndi quinalcolic acid ndi didehydroalanine tail precursor. Kenako adayeretsa mankhwalawa kuti apezethiostrepton.
Owunikanso mapepala awiri a gululo anati kupanga kumeneku “ndi ntchito yabwino kwambiri yomwe ikuwonetsa ukadaulo wamakono ndikutsegula njira zatsopano zofufuzira bwino kapangidwe kake, ntchito, ndi njira yogwirira ntchito.”