Ukutholakala Nokuthuthukiswa KweThiostrepton

       I-Thiostreptonumkhiqizo webhaktheriya wemvelo oyinkimbinkimbi kakhulu osetshenziswa njengekhambi lokwelaphai-antibiotic yezilwanefuthi inomsebenzi omuhle wokulwa nomalaleveva kanye nomdlavuza. Njengamanje, yenziwe ngamakhemikhali ngokuphelele.
I-Thiostrepton, eyaqala ukuhlukaniswa namagciwane ngo-1955, inomsebenzi ongavamile wama-antibiotic: ivimbela ukwenziwa kwamaprotheni ngokubopha ku-ribosomal RNA kanye namaprotheni ahlobene nawo. UDorothy Crowfoot Hodgkin, isazi sekristalu saseBrithani kanye nomnqobi weNobel Prize ka-1964, wathola lesi sakhiwo ngo-1970.
I-Thiostrepton iqukethe izindandatho eziyi-10, izibopho ze-peptide eziyi-11, ukungagcwali okukhulu, kanye nama-stereocenters ayi-17. Okuyinselele nakakhulu ukuthi ibucayi kakhulu kuma-acid kanye nezisekelo. Ingumzali futhi iyilungu eliyinkimbinkimbi kakhulu lomndeni wama-antibiotic we-thiopeptide.
Manje le nhlanganisela isinqotshwe inkulumo emnandi yokwenziwa kaprofesa wekhemistri uKS Nicolaou kanye nozakwabo abavela eScripps Research Institute kanye naseNyuvesi yaseCalifornia eSan Diego [Angew. Chem. internationality. Abahleli, 43, 5087 kanye no-5092 (2004)].
UChristopher J. Moody, uMcwaningi Omkhulu eMnyangweni Wekhemistri eNyuvesi yase-Exeter, e-UK, uphawule wathi: “Lokhu kuwukuhlanganiswa okuphawulekayo kanye nempumelelo emangalisayo yeqembu likaNicolaou.” doxorubicin D.
Isihluthulelo sesakhiwo seI-THIOSTREPTONyindandatho ye-dehydropiperidine, esekela umsila we-didehydroalanine kanye nama-macrocycle amabili - indandatho equkethe i-thiazoline enamalungu angu-26 kanye nohlelo lwe-quinalcolic acid olunamalungu angu-27. UNicolaou kanye nozakwabo bakhe indandatho eyinhloko ye-dehydropiperidine ngezinto ezilula zokuqala besebenzisa ukusabela kwe-biomimetic iso-Diels-Alder dimerization. Lesi sinyathelo esibalulekile sasiza ukuqinisekisa isiphakamiso sango-1978 sokuthi amabhaktheriya asebenzise lokhu kusabela kuma-antibiotic e-thiopeptide e-biosynthesize.
UNicolaou kanye nozakwabo bafaka i-dehydropiperidine ku-macrocycle equkethe i-thiazoline. Bahlanganisa le macrocycle nesakhiwo esiqukethe i-quinalcolic acid kanye ne-didehydroalanine tail precursor. Base behlanza umkhiqizo ukuze batholei-thiostrepton.
Ababuyekezi bamaphepha amabili eqembu bathi ukuhlanganiswa “kuwumsebenzi wobuciko oqokomisa ubuchwepheshe besimanje futhi kuvula amathuba amasha ocwaningo olunenjongo mayelana nesakhiwo, umsebenzi, kanye nendlela yokwenza.”