Straightforward Synthesis of the Poly(ADP-ribose) Branched Core Structure

Rui Hagino; Keita Mozaki; Naoko Komura; Akihiro Imamura; Hideharu Ishida; Hiromune Ando; Hide-Nori Tanaka

doi:10.1021/acsomega.2c04732

Straightforward Synthesis of the Poly(ADP-ribose) Branched Core Structure

ACS Omega. 2022 Sep 5;7(36):32795-32804. doi: 10.1021/acsomega.2c04732. eCollection 2022 Sep 13.

Authors

Rui Hagino^{1

2}, Keita Mozaki², Naoko Komura³, Akihiro Imamura^{3

1

2}, Hideharu Ishida^{3

1

2}, Hiromune Ando^{3

1}, Hide-Nori Tanaka^{3

1}

Affiliations

¹ The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
² Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
³ Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.

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-(1‴ → 2″)-α-d-ribofuranosyl-(1″ → 2')-adenosine 5',5'',5‴-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.