An Efficient and Sustainable Synthesis of the Antimalarial Drug Tafenoquine

Overview

Journal ACS Sustain Chem Eng

Publisher American Chemical Society

Date 2022 Dec 26

PMID 36569493

Authors

Rahul D Kavthe

Joseph R A Kincaid

Bruce H Lipshutz

Affiliations

Soon will be listed here.

Abstract

An 11-step, 8-pot synthesis of the antimalarial drug tafenoquine succinate was achieved in 42% overall yield using commercially available starting materials. Compared to the previous manufacturing processes that utilize environmentally egregious organic solvents and toxic reagents, the current route features a far greener (as measured by Sheldon's E Factors) and likely more economically attractive sequence, potentially expanding the availability of this important drug worldwide.

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References

DAVIDSON Jr D, Ager A, Brown J, Chapple F, Whitmire R, ROSSAN R . New tissue schizontocidal antimalarial drugs. Bull World Health Organ. 1981; 59(3):463-79. PMC: 2396075. View

Brueckner R, Lasseter K, Lin E, Schuster B . First-time-in-humans safety and pharmacokinetics of WR 238605, a new antimalarial. Am J Trop Med Hyg. 1998; 58(5):645-9. DOI: 10.4269/ajtmh.1998.58.645. View

LaMontagne M, Blumbergs P, Smith D . Antimalarials. 16. Synthesis of 2-substituted analogues of 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline as candidate antimalarials. J Med Chem. 1989; 32(8):1728-32. DOI: 10.1021/jm00128a010. View

Walsh P, Li H, de Parrodi C . A green chemistry approach to asymmetric catalysis: solvent-free and highly concentrated reactions. Chem Rev. 2007; 107(6):2503-45. PMC: 2525622. DOI: 10.1021/cr0509556. View

Peters W . The evolution of tafenoquine--antimalarial for a new millennium?. J R Soc Med. 2000; 92(7):345-52. PMC: 1297286. DOI: 10.1177/014107689909200705. View

Kincaid J, Caravez J, Iyer K, Kavthe R, Fleck N, Aue D . A sustainable synthesis of the SARS-CoV-2 M inhibitor nirmatrelvir, the active ingredient in Paxlovid. Commun Chem. 2022; 5(1):156. PMC: 9685088. DOI: 10.1038/s42004-022-00758-5. View

Sai K, Gilbert T, Klumpp D . Knorr cyclizations and distonic superelectrophiles. J Org Chem. 2007; 72(25):9761-4. DOI: 10.1021/jo7013092. View

Lee N, Bikovtseva A, Cortes-Clerget M, Gallou F, Lipshutz B . Carbonyl Iron Powder: A Reagent for Nitro Group Reductions under Aqueous Micellar Catalysis Conditions. Org Lett. 2017; 19(24):6518-6521. DOI: 10.1021/acs.orglett.7b03216. View

Vijayan K, Wei L, Glennon E, Mattocks C, Bourgeois N, Staker B . Host-targeted Interventions as an Exciting Opportunity to Combat Malaria. Chem Rev. 2021; 121(17):10452-10468. DOI: 10.1021/acs.chemrev.1c00062. View

10.

Lazuen Garay A, Pichon A, James S . Solvent-free synthesis of metal complexes. Chem Soc Rev. 2007; 36(6):846-55. DOI: 10.1039/b600363j. View

11.

. Practical chemotherapy of malaria. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser. 1990; 805:1-141. View

12.

Kincaid J, Kavthe R, Caravez J, Takale B, Thakore R, Lipshutz B . Environmentally Responsible and Cost-Effective Synthesis of the Antimalarial Drug Pyronaridine. Org Lett. 2022; 24(18):3342-3346. PMC: 9112334. DOI: 10.1021/acs.orglett.2c00944. View

13.

Martins M, Frizzo C, Moreira D, Buriol L, Machado P . Solvent-free heterocyclic synthesis. Chem Rev. 2009; 109(9):4140-82. DOI: 10.1021/cr9001098. View

14.

Lu K, Derbyshire E . Tafenoquine: A Step toward Malaria Elimination. Biochemistry. 2020; 59(8):911-920. PMC: 8034837. DOI: 10.1021/acs.biochem.9b01105. View

15.

Tanaka K, Toda F . Solvent-free organic synthesis. Chem Rev. 2001; 100(3):1025-74. DOI: 10.1021/cr940089p. View

16.

Hayashi Y . Time Economy in Total Synthesis. J Org Chem. 2020; 86(1):1-23. DOI: 10.1021/acs.joc.0c01581. View

17.

Lipshutz B, Ghorai S, Abela A, Moser R, Nishikata T, Duplais C . TPGS-750-M: a second-generation amphiphile for metal-catalyzed cross-couplings in water at room temperature. J Org Chem. 2011; 76(11):4379-91. PMC: 3608414. DOI: 10.1021/jo101974u. View

18.

Hayashi Y . Pot economy and one-pot synthesis. Chem Sci. 2017; 7(2):866-880. PMC: 5529999. DOI: 10.1039/c5sc02913a. View

19.

Hounkpatin A, Kreidenweiss A, Held J . Clinical utility of tafenoquine in the prevention of relapse of malaria: a review on the mode of action and emerging trial data. Infect Drug Resist. 2019; 12:553-570. PMC: 6411314. DOI: 10.2147/IDR.S151031. View

20.

Puri S, Dutta G . Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys. Acta Trop. 2003; 86(1):35-40. DOI: 10.1016/s0001-706x(02)00289-9. View