Citation: Tong Xi, Tao Qingli, Liu Fengrui, Tang Fengxiang. Advances in the Synthesis of Venetoclax as a New Drug for the Treatment of Chronic Lymphocytic Leukemia[J]. Chemistry, ;2018, 81(2): 116-121. shu

Advances in the Synthesis of Venetoclax as a New Drug for the Treatment of Chronic Lymphocytic Leukemia

Department of Chemistry, Fuzhou University, Fuzhou 350116

Corresponding author: Tang Fengxiang, hellotfx@fzu.edu.cn
Received Date: 27 July 2017
Accepted Date: 31 October 2017

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Venetoclax, the first selective inhibitor of B-cell lymphoma-2, was approved by FDA for treating relapsed or refractory chronic lymphocytic leukemia patients with 17p deletion who have received at least one prior therapy. In this paper, four reported synthesis routes of Venetoclax are reviewed. The comparison and analysis of these synthesis routes showed that convergent strategies are often applied in the synthesis of Venetoclax, and it includes the synthesis of four kinds of key intermediates. The synthesis routes of Venetoclax are continuously improved in these respects of using cheap and readily available raw materials, raw materials or synthesis approaches with higher reaction selectivity, milder reaction conditions and enhancing gross yields. In view of the fact that all of the four synthesis routes involve precious metal (palladium) and ligands as catalysts, investigation of polymer-supported palladium and ligands as catalysts will simplify the recovery of catalysts and separation process, and further decrease the preparation cost. This also helps to the development of sustainable industrial production of Venetoclax. If this improvement is accomplished, the fourth synthesis route of Venetoclax has the greatest potential for industrialization.
- Chronic lymphocytic leukemia,
- Venetoclax,
- Synthesis
1. [1]
  S Devereux, K Cuthill. Medicine, 2017, 45(5): 292~296.
2. [2]
  L Scarfò, A J M Ferreri, P Ghia. Crit. Rev. Oncol. Hematol., 2016, 104: 169~182.
3. [3]
  S D Cang, C Iragavarapu, J Savooji et al. J. Hematol. Oncol., 2015, 8: 129~136.
4. [4]
  J K Bruelle, A Letai. J. Cell Sci., 2009, 122(4): 437~441.
5. [5]
  R W Birkinshaw, P E Czabotar. Semin. Cell Dev. Biol., 2017, (https://doi.org/10.1016/j.semcdb.2017.04.001).
6. [6]
  V Brower. Lancet Oncol., 2016, 17(1): e11.
7. [7]
8. [8]
9. [9]
  D L Hughes. Org. Process Res. Dev., 2016, 20: 2028~2042.
10. [10]
  N D Catron, D J Lindley, J Miller et al. WO: 2012058392, 2012.
11. [11]
  N D Catron, S Chen, Y C Gong et al. WO: 2012071336, 2012.
12. [12]
  M Bruncko, H Ding, G A Doherty et al. US: 8546399, 2013.
13. [13]
  M Bruncko, H Ding, G A Doherty et al. US: 9174982, 2015.
14. [14]
  G A Doherty, S W Elmore, L Wang et al. US: 8580794, 2013.
15. [15]
  N D Catron, S Chen, Y Gong et al. US: 8722657, 2014.
16. [16]
  V S Chan, T A Grieme, Y Y Ku et al. US: 20140275540, 2014.
17. [17]
  V S Chan, T A Grieme, A C Christensen et al. US: 9199992, 2015.
18. [18]
19. [19]
1. [1]
  Bin SUN , Heyan JIANG . Glucose-modified bis-Schiff bases: Synthesis and bio-activities in Alzheimer′s disease therapy. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1338-1350. doi: 10.11862/CJIC.20240428
2. [2]
  Liangyu Zhang , Lei Lei , Zhuangzhuang Zhao , Guizhi Yang , Kaitao Wang , Liying Wang , Ningxin Zhang , Yanjia Ai , Xinqing Ma , Guannan Liu , Meng Zhao , Jun Wu , Dongjun Lin , Chun Chen . Enhanced venetoclax delivery using l-phenylalanine nanocarriers in acute myeloid leukemia treatment. Chinese Chemical Letters, 2025, 36(6): 110316-. doi: 10.1016/j.cclet.2024.110316
3. [3]
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4. [4]
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5. [5]
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6. [6]
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7. [7]
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8. [8]
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9. [9]
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14. [14]
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18. [18]
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20. [20]
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