Ivumburwa n'iterambere rya Thiostrepton

       Thiostreptonni umuti ugoye cyane wa bagiteri karemano ukoreshwa nk'umuti wo mu bwoko bwa "topical treatment"imiti igabanya ubukana bw'amatungokandi ifite imikorere myiza yo kurwanya malariya no kurwanya kanseri. Kuri ubu, ikorwa mu buryo bwuzuye mu buryo bwa shimi.
Thiostrepton, yakuwe bwa mbere muri bagiteri mu 1955, ifite imikorere idasanzwe ya antibiyotike: ibuza poroteyine gukorana na RNA ya ribosomal na poroteyine zifitanye isano nayo. Dorothy Crowfoot Hodgkin, umuhanga mu by'ubutare bw'umwongereza akaba n'uwatsindiye igihembo cya Nobel mu 1964, yavumbuye iyi miterere mu 1970.
Thiostrepton igizwe n'impeta 10, imigozi 11 ya peptide, kudakomeza kwuzuza neza, hamwe n'ibice 17 by'ingenzi. Ikigoye kurushaho ni uko ikunda cyane aside na base. Ni yo mvaruganda kandi ikaba ari yo igoranye cyane mu muryango wa antibiyotike za thiopeptide.
Ubu iyi mvange yamaze kwigarurira imvugo nziza ya porofeseri KS Nicolaou na bagenzi be bo mu kigo cy’ubushakashatsi cya Scripps na Kaminuza ya California i San Diego [Angew. Chem. internationality. Editors, 43, 5087 na 5092 (2004)].
Christopher J. Moody, Umushakashatsi Mukuru mu Ishami rya Chimie muri Kaminuza ya Exeter, mu Bwongereza, yagize ati: “Iki ni igikorwa cy’ingenzi cyakozwe n’itsinda rya Nicolaou.” doxorubicin D.
Urufunguzo rw'imiterere yaTHIOSTREPTONni impeta ya dehydropiperidine, ishyigikira umurizo wa didehydroalanine n'udukoko tubiri twa macrocycles - impeta irimo thiazoline ifite ibice 26 na sisitemu ya aside quinalcolic ifite ibice 27. Nicolaou na bagenzi be bakoze impeta y'ingenzi ya dehydropiperidine bakoresheje ibikoresho byoroshye byo gutangira bakoresheje uburyo bwa biomimetic iso-Diels-Alder dimerization reaction. Iyi ntambwe y'ingenzi yafashije kwemeza igitekerezo cyo mu 1978 cy'uko bagiteri zikoresha ubu buryo mu gukora antibiyotike za thiopeptide.
Nicolaou na bagenzi be bashyize dehydropiperidine muri macrocycle irimo thiazoline. Bahuje iyi macrocycle n'imiterere irimo aside quinalcolic na didehydroalanine tail precursor. Hanyuma basukuye umusaruro kugira ngo babonethiostrepton.
Abasesenguzi b'inyandiko ebyiri z'itsinda bavuze ko iyi sesengura “ari igikorwa cy'ubuhanga kigaragaza ikoranabuhanga rigezweho kandi gifungura icyerekezo gishya cy'ubushakashatsi bufite ishingiro ku miterere, ibikorwa, n'uburyo bw'ibikorwa.”