Thiostreptonumkhiqizo webhaktheriya wemvelo oyinkimbinkimbi kakhulu osetshenziswa njengesihlokoi-antibiotic yezilwanefuthi inomsebenzi omuhle wokulwa nomalaleveva kanye nowokunqanda umdlavuza.Njengamanje, ihlanganiswe ngokuphelele ngamakhemikhali.
I-Thiostrepton, eyaqala ukuhlukaniswa namagciwane ngo-1955, inomsebenzi ongavamile wama-antibiotic: ivimbela i-protein biosynthesis ngokubophezela ku-ribosomal RNA kanye namaprotheni ahlobene nayo.UDorothy Crowfoot Hodgkin, umdwebi wamakristalu waseBrithani futhi owawina uMklomelo kaNobel ka-1964, wathola lesi sakhiwo ngo-1970.
I-Thiostrepton iqukethe izindandatho ezingu-10, amabhondi e-peptide angu-11, ukungagcwalisi okuningi, kanye nama-stereocenters angu-17.Okuyinselele nakakhulu ukuthi izwela kakhulu kuma-asidi nezisekelo.Yinhlanganisela yomzali kanye nelungu eliyinkimbinkimbi kakhulu lomndeni we-thiopeptide antibiotic.
Manje le nhlanganisela isiye yanqotshwa inkulumo emnandi yokwenziwa kaprofesa wamakhemikhali u-KS Nicolaou kanye nozakwabo baseScripps Research Institute kanye neNyuvesi yaseCalifornia eSan Diego [Angew.I-Chem.amazwe ngamazwe.Abahleli, 43, 5087 kanye 5092 (2004)].
UChristopher J. Moody, Osebenza naye Omkhulu Wokucwaninga eMnyangweni Wezekhemikhali eNyuvesi yase-Exeter, e-UK, waphawula: “Lokhu ukuhlanganisa okuyingqopha-mlando kanye nempumelelo emangalisayo yeqembu likaNicolaou.”doxorubicin D.
Isihluthulelo sesakhiwo seTHIOSTREPTONiyindandatho ye-dehydropiperidine, esekela umsila we-didehydroalanine kanye nama-macrocycle amabili - indandatho enamalungu angama-26 ene-thiazoline kanye nesistimu ye-quinalcolic acid enamalungu angama-27.U-Nicolaou nozakwabo bakhe indandatho eyinhloko ye-dehydropiperidine ngezinto zokuqalisa ezilula besebenzisa i-biomimetic iso-Diels–Alder dimerization reaction.Lesi sinyathelo esibalulekile sasiza ukuqinisekisa isiphakamiso sango-1978 sokuthi amagciwane asebenzise lokhu kusabela ku-biosynthesize thiopeptide antibiotics.
U-Nicolaou nozakwabo bahlanganise i-dehydropiperidine ku-macrocycle equkethe i-thiazoline.Bahlanganisa le macrocycle nesakhiwo esine-quinalcolic acid kanye nesandulela somsila we-didehydroalanine.Babe sebehlanza umkhiqizo ukuze batholei-thiostrepton.
Ababuyekezi bamaphepha amabili aleli qembu bathi le nhlanganisela “iwumsebenzi wobuciko ogqamisa ubuchwepheshe besimanje futhi ivula ama-horizons amasha ukuze kwenziwe ucwaningo olunengqondo ngesakhiwo, umsebenzi, nendlela yokwenza.”
Isikhathi sokuthumela: Oct-31-2023