Straightforward Synthesis of the Poly(ADP-ribose) Branched Core Structure.
ACS Omega
; 7(36): 32795-32804, 2022 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-36119971
ABSTRACT
Poly(ADP-ribosyl)ation is a post-translational modification that produces poly(ADP-ribose) with a branched structure every 20-50 units; such branching structure has been previously suggested to be involved in regulating chromatin remodeling. To elucidate its detailed functions, we developed a straightforward method for the synthesis of the poly(ADP-ribose) branched core structure, α-d-ribofuranosyl-(1â´ â 2â³)-α-d-ribofuranosyl-(1â³ â 2')-adenosine 5',5'',5â´-trisphosphate 1, from 6-chloropurine ribofuranoside 4 in 10 steps and 6.1% overall yield. The structure poses synthetic challenges for constructing iterative α-1,2-cis-glycosidic bonds in the presence of a purine base and the installation of three phosphate groups at primary hydroxyl groups. Iterative glycosidic bonds were formed by α-1,2-cis-selective ribofuranosylation using 2-O-(2-naphthylmethyl)-protected thioglycoside donor 6 and a thiophilic bismuth promoter. After the construction of diribofuranosyl adenosine 5 had been constructed, it was chemo- and regioselectively phosphorylated at a later stage. Subsequent deprotection provided the synthetic target 1.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article