Studies of continuous-flow synthesis of nonpeptidal bistetrahydrofuran moiety of Darunavir

Studies of continuous-flow synthesis of nonpeptidal bistetrahydrofuran moiety of Darunavir

Leão, Raquel A. C.; Gosmann, Grace; Muniz, Mauro N.; Miranda, Leandro S. de M. e; Souza, Rodrigo O. M. A. de

Abstract:

The AIDS (acquired immunodeficiency syndrome) has become one of the most pressing medical concerns of our time. Specifically, the critical function of HIV protease has made it an important target for the treatment of HIV/AIDS. The approval of the first protease inhibitor (PI), saquinavir and its introduction into highly active antiretroviral therapy (HAART), with reverse transcriptase inhibitors, led to significantly enhanced HIV management and improved the quality of life of HIV/ AIDS patients. The future management of HIV/AIDS should rely upon the development of therapies that are less toxic and more effective in combating drugresistance. In this context, the Darunavir have enjoyed a surge in popularity as a new generation of PIs bearing a structure-based designed bis-THF ligand that effectively fills in the hydrophobic pocket and maximizes hydrogen bonding interactions with the backbone atoms of the S2-site. A number of bis-THF-derived inhibitors are exceedingly potent and have maintained very impressive potency against multidrug-resistant HIV-1 variants. We are interested in the use of continuous-flow approach in order to prepare the bis-THF moiety of PIs. This approach will allow a cascade effect by doing the reduction and the acetylation steps in a closed system.

The AIDS (acquired immunodeficiency syndrome) has become one of the most pressing medical concerns of our time. Specifically, the critical function of HIV protease has made it an important target for the treatment of HIV/AIDS. The approval of the first protease inhibitor (PI), saquinavir and its introduction into highly active antiretroviral therapy (HAART), with reverse transcriptase inhibitors, led to significantly enhanced HIV management and improved the quality of life of HIV/ AIDS patients. The future management of HIV/AIDS should rely upon the development of therapies that are less toxic and more effective in combating drugresistance. In this context, the Darunavir have enjoyed a surge in popularity as a new generation of PIs bearing a structure-based designed bis-THF ligand that effectively fills in the hydrophobic pocket and maximizes hydrogen bonding interactions with the backbone atoms of the S2-site. A number of bis-THF-derived inhibitors are exceedingly potent and have maintained very impressive potency against multidrug-resistant HIV-1 variants. We are interested in the use of continuous-flow approach in order to prepare the bis-THF moiety of PIs. This approach will allow a cascade effect by doing the reduction and the acetylation steps in a closed system.

Palavras-chave:

DOI: 10.5151/chempro-15bmos-BMOS2013_2013101710110

Referências bibliográficas

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• [3] 3 B. D. Doan, R. D. Davis, T. Chaiborne Patent US 2004/0204595 A1, oct. 14, 2004.

Como citar:

Leão, Raquel A. C.; Gosmann, Grace; Muniz, Mauro N.; Miranda, Leandro S. de M. e; Souza, Rodrigo O. M. A. de; "Studies of continuous-flow synthesis of nonpeptidal bistetrahydrofuran moiety of Darunavir", p-134-134. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013101710110