Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway.
Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway.
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DOI：
10.26434/chemrxiv.11553597.v1
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
S. Reilly;F. Bennett;P. Fier;S. Ren;N. Strotman
中科院分区：
文献类型：
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作者：
S. Reilly;F. Bennett;P. Fier;S. Ren;N. Strotman
开发了一种采用相应未标记分子作为起始材料的磺胺类药物的后期18o标记方法。对磺胺进行脱胺反应后，利用环境友好型试剂h218o和15nh3 （aq）对亚硫酸盐中间体进行同位素富集，得到母体化合物的M+5同位素。这种降解-重建方法为稳定同位素标记（SIL）磺胺类药物提供了高达96%的分离产率，并且与多种上市治疗药物兼容，包括塞来昔布，以克为单位。SIL产品在极端条件下也没有18 O/ 16 O回交换，进一步验证了这种绿色策略在体外和体内使用的药物标签的实用性。该程序也适用于包括药学上相关的甲基砜，通过使用13 ch3，提供M+5同位素富集，从而说明了该方法的广泛实用性。
A late-stage 18 O labeling approach of sulfonamides that employs the corresponding unlabeled molecule as the starting material was developed. Upon deamination of the sulfonamide, a sulfinate intermediate was isotopically enriched using eco-friendly reagents H 2 18 O and 15 NH 3 (aq) to afford a M+5 isotopologue of the parent compound. This degradation-reconstruction approach afforded isolated yields of up to 96% for the stable isotope labeled (SIL) sulfonamides, and was compatible with multiple marketed therapeutics, including celecoxib, on a gram scale. The SIL products also exhibited no 18 O/ 16 O back exchange under extreme conditions, further validating the utility of this green strategy for drug labeling for both in vitro and in vivo use. This procedure was also adapted to include pharmaceutically relevant methyl sulfones by using 13 CH 3 , affording M+5 isotopic enrichment, thereby illustrating the broad utility of this methodology.