Research ArticleORGANIC CHEMISTRY

Bioinspired design of a robust d3-methylating agent

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Science Advances  08 May 2020:
Vol. 6, no. 19, eaba0946
DOI: 10.1126/sciadv.aba0946

Abstract

Methods to incorporate deuterium atoms into organic molecules are valuable for the pharmaceutical industry. The introduction of deuterium atoms by a synthetic method enables the direct tracing of the drug molecule without substantially altering its structure or function. The methyl group is one of the most commonly occurring carbon fragments in biologically active molecules. Here, a biomimetic design reagent, 5-(methyl-d3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT), as an analog of S-adenosylmethionine (SAM), has been developed for the selective d3-methylation of complex molecules bearing several possible reactive sites with excellent selectivity and high-level deuterium incorporation. A series of d3-methylated organic molecules and deuterated pharmaceuticals were synthesized under the mild system with excellent functional group compatibility.

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