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.

Attempts to synthesize a trimeric derivative of pristimerin with potential activity against cancer cells

“…The 1 H and 13 C-NMR spectra were recorded at 400 and 100 MHz, respectively, using a Brüker DRX400 AVANCE spectrometer and CDCl3 or DMSO were used as solvent. The chemical shift assignments were registered in ppm () using tetramethylsilane (TMS) as the internal reference (H = c = 0), and the coupling constants (J) were registered in Hertz (Hz) (Dos Santos et al, 2024).…”

“…Four different immobilized lipases, including immobilized lipase B from Candida antarctica, as well as the protease alpha-chymotrypsin, were employed in varied conditions, such as different solvents, temperatures, and reaction times. However, all attempts to convert pristimerin in celastrol were found to be unsuccessful (Dos Santos et al, 2024).…”