Organic Synthesis Service, Medicinal Chemistry Platform, University Hospital Center (CHU), Quebec-Research Center, Québec, QC, G1V 4G2, Canada.
Toxicology Center (CTQ), National Institute of Public Health of Quebec (INSPQ), Quebec, QC. GIV 5B3, Canada.
Curr Org Synth. 2022;19(7):838-845. doi: 10.2174/1570179419666220426104848.
The syntheses of glucuronide metabolites of phenolic xenoestrogens triclosan and 2-phenylphenol, namely triclosan-O-glucuronide (TCS-G; 1), and 2-phenylphenol-Oglucuronide (OPP-G; 2), were achieved for use as analytical standards.
Under classical conditions previously reported for glucuronide synthesis, the final basic hydrolysis of the peracylated ester intermediate leading to the free glucuronides is often a limiting step. Indeed, the presence of contaminating by-products resulting from ester elimination has often been observed during this step. This is particularly relevant when the sugar unit is close to a crowded environment as for triclosan and 2-phenylphenol.
To circumvent these problems, we proposed mild conditions for the deprotection of peracetylated glucuronate intermediates.
A new methodology using a key imidate following a two-step protocol for acetates and methyl ester hydrolysis was successfully applied to the preparation of TCS-d3 (1) and OPP-G (2) as well as deuterated isotopomers TCS-d3-G (1-d3) and OPP-d5-G (2-d5).
合成酚类外源性雌激素三氯生和 2-苯苯酚的葡萄糖醛酸代谢物，即三氯生-O-葡萄糖醛酸（TCS-G；1）和 2-苯苯酚-O-葡萄糖醛酸（OPP-G；2），用作分析标准品。
在先前报道的用于葡萄糖醛酸合成的经典条件下，导致游离葡萄糖醛酸的过酰化酯中间体的最终碱性水解通常是一个限制步骤。事实上，在这一步中经常观察到由于酯消除而产生的杂质副产物的存在。当糖单元接近拥挤的环境时，这一点尤其重要，如三氯生和 2-苯苯酚。
为了避免这些问题，我们提出了温和的条件来保护过乙酰化葡萄糖醛酸盐中间体。
一种新的方法学使用关键的亚氨基随后进行两步法用于乙酸盐和甲酯水解，成功地应用于制备 TCS-d3（1）和 OPP-G（2）以及氘代同位素 TCS-d3-G（1-d3）和 OPP-d5-G（2-d5）。
