JACS: the research group of Professor Liu Wenbo of Wuhan University has made progress in the efficient synthesis of deuterium compounds

The Journal of the American Chemical Society recently published online the latest research results of Professor Liu Wenbo's research group in the school of chemistry and molecular science of Wuhan University on the opposite side of dehalogenation deuterium reaction This paper is entitled "general and practical potassium methoxide / diselane mediated dehalogenation of aryhalides (DOI: 10.1021 / JACS 8b07597)." The first author is Wang Xin, a doctoral student, Zhu Minghui, an undergraduate, and Professor Liu Wenbo, a corresponding author Since the C-D bond is more stable than the C-H bond, the substitution of deuterium for the active sites of drug molecules may significantly prolong the drug metabolism time and reduce the dosage The selective introduction of deuterium into traditional drug molecules or lead compounds is one of the hot spots in new drug research and development in recent years (Figure 1) For example, in 2017, Tyva's first deuterium drug (sd-809) for the treatment of Huntington's chorea was approved by the U.S Food and Drug Administration (FDA) In addition, deuterium compounds, due to their unique spectral properties, are widely used in reaction intermediate labeling, biological metabolism analysis, natural product source synthesis verification, pesticide residue detection and pollution source tracking Figure 1: the cheap and easily available reductive dechlorination reaction of several deuterium drug molecules (source: J am Chem SOC.) on the market or in clinical research It is one of the most effective methods to prepare deuterium compounds, but the known routes mainly use highly active and flammable lithium metal reagents, or use highly toxic transition metal and tin reagents In addition, these methods have poor compatibility with some sensitive functional groups such as amide, carbonyl, cyano, etc Therefore, it is of great significance to develop a highly selective deuterium method with mild, high efficiency and strong substrate universality Professor Liu Wenbo's group has recently developed a dehalogenation reaction using hexamethyldisilane and potassium carbinol as medium and deuterium acetonitrile as deuterium source This reaction can realize the accurate synthesis of high added value deuterium molecules at room temperature, and it has been successfully applied to the highly selective deuterium generation of heterocycles, leading drug molecules, natural product analogues, etc (Fig 2) This method does not need transition metal to participate in, and effectively avoids environmental pollution and heavy metal residues in the product It has obvious advantages and potential application value in the later modification of drug molecules Figure 2: synthesis of deuterium compounds mediated by potassium methoxide / disilane (source: J am Chem SOC.) this research has received strong support from NSFC, Wuhan University High Level Talents Program, youth thousand talents program of the central organization department and other projects.