IThiostreptonyimveliso yendalo entsonkothileyo kakhulu yebhaktheriya esetyenziswa njengeyeza lokuthambisaamayeza okubulala iintsholongwane kwizilwanyanakwaye ikwanomsebenzi omhle wokulwa nemalariya kunye nomhlaza. Okwangoku, yenziwe ngokupheleleyo ngamakhemikhali.
I-Thiostrepton, eyaqala ukususwa kwiibhaktheriya ngo-1955, inomsebenzi ongaqhelekanga wokubulala iintsholongwane: ithintela i-biosynthesis yeproteni ngokubophelela kwi-ribosomal RNA kunye neeproteni ezinxulumene nayo. UDorothy Crowfoot Hodgkin, ingcali yekristale yaseBritane kunye nophumelele iMbasa yeNobel ngo-1964, wafumanisa esi sakhiwo ngo-1970.
I-Thiostrepton ineendandatho ezili-10, iibhondi ze-peptide ezili-11, ukungagcwali kakuhle, kunye nee-stereocenters ezili-17. Eyona nto inzima ngakumbi kukuba ibuthathaka kakhulu kwii-asidi kunye nee-bases. Yinto engumzali kwaye lilungu elinzima kakhulu losapho lwe-antibiotic ye-thiopeptide.
Ngoku le khompawundi iye yawela kwintetho emnandi yokwenziwa nguprofesa wekhemistri uKS Nicolaou kunye noogxa bakhe abavela kwiScripps Research Institute kunye neYunivesithi yaseCalifornia eSan Diego [Angew. Chem. internationality. Abahleli, 43, 5087 kunye no-5092 (2004)].
UChristopher J. Moody, uMfundi oPhezulu kwiSebe leKhemistri kwiYunivesithi yase-Exeter, e-UK, uthe: “Olu luhlanganisi olubalulekileyo kunye nempumelelo emangalisayo yeqela laseNicolaou.” doxorubicin D.
Isitshixo kwisakhiwo seITHIOSTREPTONyiringi ye-dehydropiperidine, exhasa umsila we-didehydroalanine kunye nee-macrocycles ezimbini - iringi ene-thiazoline enamalungu angama-26 kunye nenkqubo ye-quinalcolic acid enamalungu angama-27. UNicolaou kunye noogxa bakhe benze iringi ye-dehydropiperidine ephambili ngezinto ezilula zokuqala besebenzisa i-biomimetic iso-Diels-Alder dimerization reaction. Eli nyathelo libalulekileyo lanceda ukuqinisekisa isindululo sika-1978 sokuba iibhaktheriya zisebenzise le reaction kwi-biosynthesize thiopeptide antibiotics.
UNicolaou kunye noogxa bakhe badibanise i-dehydropiperidine kwi-macrocycle equlethe i-thiazoline. Badibanise le macrocycle kunye nesakhiwo esine-quinalcolic acid kunye ne-didehydroalanine tail precursor. Emva koko bacoca imveliso ukuze bafumanei-thiostrepton.
Abahlalutyi bamaphepha amabini eqela bathi olu qulunqo “lubugcisa obugqwesileyo obugxininisa ubuchwepheshe obuphezulu kwaye luvula amathuba amatsha ophando olunentsingiselo malunga nesakhiwo, umsebenzi, kunye nendlela yokwenza.”
Ixesha lokuthumela: Oktobha-31-2023