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. 2017 Aug 14;22(8):1346.
doi: 10.3390/molecules22081346.

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds

Lingjun Li  1 , Qianqian Li  2 , Shengqiang Ding  3 , Pengyang Xin  4 , Yuqin Zhang  5 , Shenlong Huang  6 , Guisheng Zhang  7
Affiliations

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds

Lingjun Li et al. Molecules. .

Abstract

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of ADP-ribosylated compounds is currently difficult due to structural complexity, easily broken pyrophosphate bond and high hydrophilicity. In this paper, ADP-ribosyl-N₃ was designed and synthesized for the first time. With ADP-ribosyl-N₃ as the key precursor, a divergent post-modification strategy was developed to prepare structurally diverse ADP-ribosylated compounds including novel nucleotides and peptides bearing ADP-ribosyl moieties.

Keywords: ADP-ribosylated compounds; divergent synthesis; nucleotides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ADP-ribose and ADP-ribosylated compounds. (A) Structure of ADP-ribose; (B) Structurally and functionally diverse ADP-ribosylated compounds.
Scheme 1
Scheme 1
Linear synthetic routes or divergent routes for the syntheses of ADP-ribosylated compounds. (A) The linear synthetic route for preparation of ADP-ribosylated compounds in literature; (B) The divergent synthetic route for preparation of ADP-ribosylated compounds in this work.
Figure 2
Figure 2
(A) Synthesis route of ADP-ribosyl-N3. Reagent and reaction conditions: (i) I2, MeOH; (ii) H+/acetone; (iii) (PhS)2POCl, TPSCl, tetrazole, Py; (iv) H3PO2, Py; (v) I2, MS, Py; (vi) 30% NH4OH; (vii) 50% HCOOH; (B) The solution stability of ADP-ribosyl-N3. Conditions: 1 mM aqueous solution of ADP-ribosyl-N3 was heated at given temperatures, and the resultant mixtures were detected by HPLC.
Figure 3
Figure 3
ADP-ribosylated compounds synthesized via divergent strategy (1,2). 1 ADP-ribosyl-N3 (0.01 mmol), terminal alkynes (0.012 mmol), 10 mol % CuSO4 and Cu(0) (copper sheet) were added in TEAB buffer (1 mL) and the reaction was stirred for 24 h at room temperature; 2 Isolated yields by semiprepartive HPLC.
Scheme 2
Scheme 2
Conjugation of ADP-ribosyl moiety to free peptide with ADP-ribosyl-N3 as a building block.
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