Thiostreptonyog ib yam khoom siv kab mob ntuj tsim uas nyuaj heev uas siv los ua tshuaj pleevtshuaj tua kab mob tsiajthiab kuj muaj cov tshuaj tua kab mob malaria thiab anticancer zoo. Tam sim no, nws yog cov tshuaj synthesized tag nrho.
Thiostrepton, thawj zaug rho tawm los ntawm cov kab mob hauv xyoo 1955, muaj cov tshuaj tua kab mob tsis tshua muaj: nws inhibits protein biosynthesis los ntawm kev khi rau ribosomal RNA thiab nws cov protein cuam tshuam. Dorothy Crowfoot Hodgkin, tus kws tshawb fawb crystallographer Askiv thiab tus yeej Nobel xyoo 1964, tau tshawb pom cov qauv hauv xyoo 1970.
Thiostrepton muaj 10 lub nplhaib, 11 peptide bonds, extensive unsaturation, thiab 17 stereocenters. Qhov nyuaj dua yog qhov tseeb tias nws rhiab heev rau cov kua qaub thiab cov hauv paus. Nws yog cov tshuaj niam txiv thiab yog cov tswv cuab nyuaj tshaj plaws ntawm tsev neeg thiopeptide tshuaj tua kab mob.
Tam sim no cov tshuaj no tau poob rau hauv kev hais lus qab zib ntawm cov xibfwb chemistry KS Nicolaou thiab nws cov npoj yaig los ntawm Scripps Research Institute thiab University of California hauv San Diego [Angew. Chem. internationality. Editors, 43, 5087 thiab 5092 (2004)].
Christopher J. Moody, Tus Kws Tshawb Fawb Qib Siab hauv Chav Haujlwm Chemistry ntawm University of Exeter, UK, tau hais tias: "Qhov no yog ib qho tseem ceeb ntawm kev sib xyaw ua ke thiab yog ib qho kev ua tiav zoo kawg nkaus los ntawm pawg Nicolaou." doxorubicin D.
Qhov tseem ceeb rau qhov kev tsim kho ntawmTHIOSREPTONyog lub nplhaib dehydropiperidine, uas txhawb nqa tus tw didehydroalanine thiab ob lub macrocycles - lub nplhaib thiazoline-muaj 26-membered thiab lub kaw lus quinalcolic acid 27-membered. Nicolaou thiab cov npoj yaig tau tsim lub nplhaib dehydropiperidine tseem ceeb los ntawm cov ntaub ntawv pib yooj yim siv cov tshuaj biomimetic iso-Diels-Alder dimerization. Cov kauj ruam tseem ceeb no tau pab lees paub qhov kev thov xyoo 1978 uas cov kab mob siv cov tshuaj no los biosynthesize thiopeptide tshuaj tua kab mob.
Nicolaou thiab cov npoj yaig tau muab dehydropiperidine tso rau hauv ib lub macrocycle uas muaj thiazoline. Lawv tau muab lub macrocycle no ua ke nrog ib lub qauv uas muaj quinalcolic acid thiab ib qho didehydroalanine tail precursor. Tom qab ntawd lawv tau ua kom cov khoom huv si kom tau txaisthiostrepton.
Cov neeg saib xyuas ob daim ntawv ntawm pawg neeg tau hais tias qhov kev sib xyaw ua ke "yog ib qho txuj ci tseem ceeb uas qhia txog cov thev naus laus zis tshiab thiab qhib lub qab ntuj tshiab rau kev tshawb fawb tseem ceeb txog cov qauv, kev ua ub no, thiab hom kev ua."
Lub sijhawm tshaj tawm: Lub Kaum Hli-31-2023