Attempts to synthesize a trimeric derivative of pristimerin with potential activity against cancer cells
Abstract
Pristimerin exhibits significant potential as a therapeutic agent, demonstrating activity against various human cancer cells. The assumption is that the trimer of pristimerin enhances the strength and selectivity of pristimerin-DNA interactions through a multivalent effect. Therefore, to synthesize the trimer of pristimerin, a multi-step route was adopted. The initial step involved the synthesis of 2-(2-(2-azidoetoxy)ethoxy)ethan-1-ol (R1) through an SN2 reaction, with a yield of 52%. The compound N-(tert-butoxyl-carbonyl)-tris-(hydroxymethyl)aminomethane (R2), with the amino group protected by tert-butoxyl carbamate, was obtained with an 87% yield and, the trialkyne, N-(tert-butoxyl-carbonyl)-tris-(propargyl)-methyl)aminomethane (R3), was obtained with a 43% yield. Despite successful synthesis of compound R1, R2 and R3, various methodologies were attempted for the transesterification between pristimerin and R1 to produce 2-(2-(2-azidoethoxy)ethoxyethyl pristimerinoate (R4), including chemical and enzymatic hydrolysis of pristimerin as an alternative route. However, none of these attempts succeeded, indicating the remarkable resistance of carbon C-29 in pristimerin to these reactions.
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Copyright (c) 2024 Josana Pereira dos Santos, Rafael César Gonçalves Pereira, Victor Hugo dos Santos, Leonardo César de Moraes, Amanda Silva de Miranda, Sidney Augusto Vieira-Filho, Lucienir Pains Duarte, Grasiely Faria de Sousa, Rute Cunha FigueiredoAuthor(s)
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Josana Pereira dos Santos
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Rafael César Gonçalves Pereira
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Victor Hugo dos Santos
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Leonardo César de Moraes
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Amanda Silva de Miranda
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Sidney Augusto Vieira-Filho
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Lucienir Pains Duarte
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Grasiely Faria de Sousa
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Rute Cunha Figueiredo