Citation: Tiantian Zhang, Hanbo Liu, Junbiao Chang, Yonggang Meng. Total synthesis of ADPr-ATP and evaluation of the antiviral activity of pRib-AMP prodrug[J]. Chinese Chemical Letters, ;2026, 37(2): 111380. doi: 10.1016/j.cclet.2025.111380 shu

Total synthesis of ADPr-ATP and evaluation of the antiviral activity of pRib-AMP prodrug

Tiantian Zhang ^{a, 1} ,
Hanbo Liu ^{b, 1} ,
Junbiao Chang ^{a, b, c, *,} ,
Yonggang Meng ^{a, b, c, *,}

a.
College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China
b.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
c.
State Key Laboratory of Antiviral Drugs, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China

changjunbiao@zzu.edu.cn

mengyonggang@zzu.edu.cn

Received Date: 10 April 2025
Revised Date: 23 May 2025
Accepted Date: 26 May 2025
Available Online: 26 May 2025

Figures(6)

ADPr-ATP is a natural nucleotide with three sugar rings and five pentavalent phosphorus, and can be produced through TIR-catalyzed ADP-ribosylation reactions for plant immunity. Here, we report the first total synthesis of ADPr-ATP (1) with a total yield of 6.4% through 14 steps, featuring late-stage P(V)−N activation reaction of pyrophosphate (4) and 5′-phosphoromorpholidate (25). The protected adenosine 5′-phosphoromorpholidate (24) was prepared on the basis of a scalable to adenosine 5′′-monophosphate (2). The construction of P(V)−N bond in phosphoramidate is esteemed as a critical step as they are sufficiently stable in deprotection reactions. The chemical synthesis of ADPr-ATP can offer an appealing alternative to traditional enzymatic synthesis and fractionation methods. Furthermore, the pRib-AMP and its prodrug are also synthesized to evaluate cytotoxicity and anti-influenza activity in vitro.
- ADPr-ATP,
- Nucleotide,
- Immunity,
- Total synthesis,
- Anti-influenza
1. [1]
  H. Yao, J. Qin, Y. Wang, et al., Chin. Chem. Lett. 35 (2024) 109154. doi: 10.1016/j.cclet.2023.109154
2. [2]
  M. Meanwell, S.M. Silverman, J. Lehmann, et al., Science 369 (2020) 725–730. doi: 10.1126/science.abb3231
3. [3]
  L. Liu, R. Chen, G. Xue, et al., Chin. Chem. Lett. 35 (2024) 108455. doi: 10.1016/j.cclet.2023.108455
4. [4]
  A. Jia, S. Huang, W. Song, et al., Science 377 (2022) eabq8180. doi: 10.1126/science.abq8180
5. [5]
  S. Huang, A. Jia, W. Song, et al., Science 377 (2022) eabq3297. doi: 10.1126/science.abq3297
6. [6]
  K. Essuman, J. Milbrandt, J.L. Dangl, et al., Science 377 (2022) eabo0001. doi: 10.1126/science.abo0001
7. [7]
  Y. Wu, W. Xu, G. Zhao, et al., Science 386 (2024) 1405–1412. doi: 10.1126/science.adr2138
8. [8]
  H. Yu, W. Xu, S. Chen, et al., Science 386 (2024) 1413–1420. doi: 10.1126/science.adr3150
9. [9]
  E.V. Efimtseva, A.A. Shelkunova, S.N. Mikhailov, et al., Nucleos. Nucleot. Nucl. 22 (2003) 1109–1111. doi: 10.1081/NCN-120022748
10. [10]
  Y. Ahmadibeni, K. Parang, Angew. Chem. Int. Ed. 56 (2007) 4739–4743. doi: 10.1002/anie.200605029
11. [11]
  L. Liang, Y. Meng, X. Chang, et al., J. Med. Chem. 68 (2025) 68 1994–2007. doi: 10.1021/acs.jmedchem.4c02769
12. [12]
  H.A.V. Kistemaker, L.N. Lameijer, N.J. Meeuwenoord, et al., Angew. Chem. Int. Ed. 54 (2015) 4915–4918. doi: 10.1002/anie.201412283
13. [13]
  M.J. Lambrecht, M. Brichacek, E. Barkauskaite, et al., J. Am. Chem. Soc. 137 (2015) 3558–3564. doi: 10.1021/ja512528p
14. [14]
  E.S. Tan, K.A. Krukenberg, T.J. Mitchison, Anal. Biochem. 428 (2012) 126–136. doi: 10.1016/j.ab.2012.06.015
15. [15]
  G.J. van der Heden van Noort, H.S. Overkleeft, G.A. van der Marel, et al., Org. Lett. 13 (2011) 2920–2923. doi: 10.1021/ol200971z
16. [16]
  S.N. Mikhailov, I.V. Kulikova, K. Nauwelaerts, Tetrahedron 64 (2008) 2871–2876. doi: 10.1016/j.tet.2008.01.028
17. [17]
  J. Ludwig, Acta Biochim. Biophys. Acad. Sci. Hung. 16 (1981) 131–133.
18. [18]
  J. Ludwig, F. Eckstein, J. Org. Chem. 54 (1989) 631–635. doi: 10.1021/jo00264a024
19. [19]
  Y. Feng, J. Yang, C. Cai, et al., Chin. Chem. Lett. 33 (2022) 4878–4881. doi: 10.1016/j.cclet.2022.02.071
20. [20]
  G.K. Wagner, T. Pesnot, R.A. Field, Nat. Prod. Rep. 26 (2009) 1172–1194. doi: 10.1039/b909621n
21. [21]
  Y. Ahmadibeni, K. Parang, Org. Lett. 7 (2005) 5589–5592. doi: 10.1021/ol0521432
22. [22]
  Q. Sun, S. Gong, J. Sun, J. Org. Chem. 79 (2013) 8417–8426. doi: 10.1021/jo4011156
23. [23]
  G. Ofir, E. Herbst, M. Baroz, et al., Nature 600 (2021) 116–120. doi: 10.1038/s41586-021-04098-7
24. [24]
  A. Bernheim, A. Millman, G. Ofir, et al., Nature 589 (2021) 120–124. doi: 10.1038/s41586-020-2762-2
25. [25]
  Q. Ye, R.K. Lau, I.T. Mathews, et al., Mol. Cell 77 (2020) 709–722. doi: 10.1016/j.molcel.2019.12.009
26. [26]
  D. Cohen, S. Melamed, A. Millman, et al., Nature 574 (2019) 691–695. doi: 10.1038/s41586-019-1605-5
1. [1]
  Tengfei Xuan , Xinyu Zhang , Wei Han , Yidong Huang , Weiwu Ren . Total synthesis of (+)-taberdicatine B and (+)-tabernabovine B. Chinese Chemical Letters, 2025, 36(2): 109816-. doi: 10.1016/j.cclet.2024.109816
2. [2]
  Qunlong Zhang , Jingyi Kang , Jingwen Wang , Tiancheng Tan , Zhaoyong Lu . Divergent total synthesis of sesquiterpene (hydro)quinone meroterpenoids dysideanones A and E–G. Chinese Chemical Letters, 2025, 36(3): 109915-. doi: 10.1016/j.cclet.2024.109915
3. [3]
  Yun-Hong Yu , Yu Peng , Wei-Dong Z. Li . Highly fused tetracyclic diterpenoid natural products: Diverse biosynthesis and total synthesis. Chinese Chemical Letters, 2025, 36(10): 111137-. doi: 10.1016/j.cclet.2025.111137
4. [4]
  Jingping Hu , Jing Xu . Total synthesis of a putative yuzurimine-type Daphniphyllum alkaloid C₁₄–epi-deoxycalyciphylline H. Chinese Chemical Letters, 2024, 35(4): 108733-. doi: 10.1016/j.cclet.2023.108733
5. [5]
  Zhenhao Wang , Yuliang Tang , Ruyu Li , Shuai Tian , Yu Tang , Dehai Li . Bioinspired synthesis of cochlearol B and ganocin A. Chinese Chemical Letters, 2024, 35(7): 109247-. doi: 10.1016/j.cclet.2023.109247
6. [6]
  Peng Chen , Lijuan Liang , Yufei Zhu , Zhimin Xing , Zhenhua Jia , Teck-Peng Loh . Strategies for constructing seven-membered rings: Applications in natural product synthesis. Chinese Chemical Letters, 2024, 35(6): 109229-. doi: 10.1016/j.cclet.2023.109229
7. [7]
  Xin Zhang , Zhihao Lu , Tianci Ren , Junxiang Tang , Shuo Li , Chenghao Zhu , Lijun Mao , Da Ma . Fluorescent "Texas-sized" macrocyclic receptors for the recognition and detection of nucleotides in water. Chinese Chemical Letters, 2025, 36(11): 110946-. doi: 10.1016/j.cclet.2025.110946
8. [8]
  Rongrong Zheng , Zuxiao Chen , Qiuyuan Li , Ni Yang , Wenjun Zhang , Chuyu Huang , Linping Zhao , Xin Chen , Hong Cheng , Shiying Li . Endoplasmic reticulum targeting photodynamic oxidizer to boost anti-tumor immunity by intensifying immunogenic cell death in conjunction with IDO1 inhibition. Chinese Chemical Letters, 2025, 36(12): 110865-. doi: 10.1016/j.cclet.2025.110865
9. [9]
  Xuan Pan , Tao Sheng , Zhanzhu Liu . A concise total synthesis of monoterpenoid indole alkaloid (-)-voacafricine A. Chinese Chemical Letters, 2025, 36(10): 110913-. doi: 10.1016/j.cclet.2025.110913
10. [10]
  Yongjuan Li , Rongrong Zhu , Yichen Guo , Yayun Wang , Rong Ma , Kunru Ma , Yongxing Zhao , Weijing Yang . Sequential-gated transformable nanoprodrug potentiates antitumor immunity through TME modulation and STING activation. Chinese Chemical Letters, 2025, 36(9): 110704-. doi: 10.1016/j.cclet.2024.110704
11. [11]
  Xiao-Gang Wang , Ai-E Wang , Pei-Qiang Huang . Corrigendum to "A concise formal stereoselective total synthesis of (–)-swainsonine" [Chin Chem Lett 25 (2014) 193–196]. Chinese Chemical Letters, 2025, 36(3): 110597-. doi: 10.1016/j.cclet.2024.110597
12. [12]
  Fengqing Wang , Changxing Qi , Chunmei Chen , Qin Li , Qingyi Tong , Weiguang Sun , Zhengxi Hu , Minyan Wang , Hucheng Zhu , Lianghu Gu , Yonghui Zhang . Discovery and enantioselective total synthesis of antitumor agent asperfilasin A via a regio- and diastereoselective Nazarov cyclization. Chinese Chemical Letters, 2025, 36(6): 110252-. doi: 10.1016/j.cclet.2024.110252
13. [13]
  Xiaohong Wen , Mei Yang , Lie Li , Mingmin Huang , Wei Cui , Suping Li , Haiyan Chen , Chen Li , Qiuping Guo . Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor. Chinese Chemical Letters, 2024, 35(8): 109291-. doi: 10.1016/j.cclet.2023.109291
14. [14]
  Jia-Mei Qin , Xue Li , Wei Lang , Fu-Hao Zhang , Qian-Yong Cao . An AIEgen nano-assembly for simultaneous detection of ATP and H₂S. Chinese Chemical Letters, 2024, 35(6): 108925-. doi: 10.1016/j.cclet.2023.108925
15. [15]
  Zhu Shu , Xin Lei , Yeye Ai , Ke Shao , Jianliang Shen , Zhegang Huang , Yongguang Li . ATP-induced supramolecular assembly based on chromophoric organic molecules and metal complexes. Chinese Chemical Letters, 2024, 35(11): 109585-. doi: 10.1016/j.cclet.2024.109585
16. [16]
  Huimin Luan , Qinming Wu , Jianping Wu , Xiangju Meng , Feng-Shou Xiao . Templates for the synthesis of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100252-100252. doi: 10.1016/j.cjsc.2024.100252
17. [17]
  Hang Wang , Qi Wang , Chuan-De Wu . Continuous synthesis of ammonia. Chinese Journal of Structural Chemistry, 2025, 44(3): 100437-100437. doi: 10.1016/j.cjsc.2024.100437
18. [18]
  Haiyang Gu , Xiang Xu . Multicolor hybrid metal halides and anti-counterfeiting. Chinese Journal of Structural Chemistry, 2024, 43(9): 100352-100352. doi: 10.1016/j.cjsc.2024.100352
19. [19]
  Yuanmao Fu , Ziang Wang , Kefan Wu , Feiyang Li , Xian Zhang , Hongyuan Cui , Xiaolin Wang , Hui Guo , Yuezhong Meng . Bio-inspired multifunctional hydrogels with adhesive, anti-bacterial, anti-icing and sensing properties. Chinese Chemical Letters, 2025, 36(7): 110479-. doi: 10.1016/j.cclet.2024.110479
20. [20]
  Zhaojun Liu , Zerui Mu , Chuanbo Gao . Alloy nanocrystals: Synthesis paradigms and implications. Chinese Journal of Structural Chemistry, 2023, 42(11): 100156-100156. doi: 10.1016/j.cjsc.2023.100156

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(9)
HTML views(0)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142