Kuvumbura no Gutezimbere kwa Thiostrepton

       Thiostreptonni ibicuruzwa bisanzwe bya bagiteri ikoreshwa nkibintu byingenziantibiyotike y'amatungokandi ifite ibikorwa byiza bya antimalarial na anticancer.Kugeza ubu, irashizwemo rwose.
Thiostrepton, yatandukanijwe bwa mbere na bagiteri mu 1955, ifite ibikorwa bya antibiyotike idasanzwe: ibuza protein biosynthesis guhuza na ribosomal RNA na poroteyine bifitanye isano nayo.Dorothy Crowfoot Hodgkin, umuhanga mu kristu w’umwongereza akaba yaratsindiye igihembo cyitiriwe Nobel mu 1964, yavumbuye imiterere mu 1970.
Thiostrepton irimo impeta 10, peptide 11, guhaga kwinshi, hamwe na stereocenters 17.Ndetse bigoye cyane ni uko yunvikana cyane acide na base.Nibigo byababyeyi kandi bigoye cyane mumuryango wa antibiotique ya thiopeptide.
Ubu uru ruganda rwatsinzwe n'ikiganiro cyiza cya professeur wa chimie KS Nicolaou na bagenzi be bo mu kigo cy’ubushakashatsi cya Scripps na kaminuza ya Californiya i San Diego [Angew.Chem.mpuzamahanga.Abanditsi, 43, 5087 na 5092 (2004)].
Christopher J. Moody, Umushakashatsi Ushinzwe Ubushakashatsi mu ishami rya Himiya muri kaminuza ya Exeter, mu Bwongereza, yagize ati: “Iyi ni sintezeza idasanzwe kandi ni ikintu kidasanzwe cyakozwe n'itsinda rya Nicolaou.”doxorubicin D.
Urufunguzo rw'imiterere yaTHIOSTREPTONni impeta ya dehydropiperidine, ishyigikira umurizo wa didehydroalanine na macrocycle ebyiri - impeta ya tiazoline igizwe n’abanyamuryango 26 hamwe na sisitemu ya acide ya quinalcolike igizwe n’abanyamuryango 27.Nicolaou na bagenzi be bakoze urufunguzo rwa dehydropiperidine kuva mubikoresho byoroshye byo gutangira ukoresheje biomimetic iso-Diels - Alder dimerization reaction.Iyi ntambwe yingenzi yafashije kwemeza icyifuzo cya 1978 ko bagiteri ikoresha iyi reaction kuri biosynthesize antibiotique ya thiopeptide.
Nicolaou na bagenzi be bashizemo dehydropiperidine muri macrocycle irimo thiazoline.Bahujije iyi macrocycle nuburyo burimo aside ya quinalcolike na didehydroalanine umurizo wabanjirije.Bahise basukura ibicuruzwa kugirango babonethiostrepton.
Abasesenguye impapuro ebyiri z'iri tsinda bavuze ko synthesis “ari igihangano cyerekana ikoranabuhanga rigezweho kandi rigafungura inzira nshya kugira ngo hakorwe ubushakashatsi bufite ireme mu miterere, ibikorwa, ndetse n'uburyo bwo gukora.”