The acyl glucuronide of 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid: Synthesis, structural assignment, occurrence as a human phase II metabolite of Uvinul® A Plus and acute aquatic toxicity.

• Tác giả: Ana M Amat, José V Castell, Salvador Gil, Virginie Lhiaubet-Vallet, Miguel A Miranda, Marta Moreno-Torres, Erika Moro, María Payá-García, Gemma M Rodríguez-Muñiz, Lucas Santos-Juanes
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Chemosphere , 2025
• Bộ sưu tập: NCBI
• ID: 713631

Tóm tắt

This work was undertaken to address the potential environmental impact of the UVA filter Uvinul® A Plus (DHHB) upon its biotransformation in humans. For this purpose, the putative human metabolite 3 was prepared by a three-step synthetic sequence involving the initial Koenigs-Knorr reaction of 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid (DHB) with acetobromo-α-d-glucuronic acid methyl ester, which afforded the corresponding peracetylated DHB-acyl glucuronide (1). Subsequent enzymatic deprotection with amano lipase A (LAS) led to the 2-(4-diethylamino-2-hydroxybenzoyl)benzoyl-β-D-glucuronide methyl ester (2). Final deprotection of compound 2 was achieved with porcine liver esterase (PLE), giving the target 2-(4-diethylamino-2-hydroxybenzoyl)benzoyl-β-D-glucuronide (3). The synthesized DHB-acyl glucuronide 3 was identical to the key phase II metabolite of DHHB in human hepatocytes. Acute toxicity of 2 and 3 was evaluated by means of the Aliivibrio fischeri bioluminescence inhibition assay, obtaining EC