Experts say that chiral amines are common in prescription drugs, such as morphine, tramadol, sertraline and plavix.
Chiral amines are compounds regarded important building blocks used in 40 percent of pharmaceutical products. Aliphatic amines, meanwhile, are used as intermediates used by the pharma industry.
For a long time, scientists have been trying to find an efficient way to synthesize chiral amines directly from aliphatic amines.
But aliphatic amines can easily be deactivated due to reactions, posing great challenges.
Scientists said a research team from Nankai University led by Professor Qi-Lin Zhou and Professor Shou-Fei Zhu has now established a novel combined catalytic system, which has solved the problem that has plagued asymmetric catalysis for more than half a century.
Recently, the internationally renowned journal Science published a research paper called "highly enantioselective carbene insertion into N–H bonds of aliphatic amines".
Scientists said the new method exhibits high yields of up to 99% and high enantioselectivity (of up to 97% ee). Furthermore it has good applicability in the modification of some drugs and bioactive molecules -- such as amoxapine, trimetazidine, vortioxetine.
They said that the product -- chiral α-amino acid derivatives -- can be used as important synthons for many chiral drugs.
According to systematic studies -- based on in-situ infrared spectroscopy, nuclear magnetic resonance and ultraviolet spectroscopy -- the researchers disclosed that there is almost no interaction between the homoscorpionate-coordinated copper complex [Tp*Cu, Tp* = hydrotris(3,5-dimethylpyrazolyl)borate] and the aliphatic amine.
They said that meanwhile the sulfur atom of the chiral thiourea catalyst (CAT) has a strong coordination with the copper complex.
The researchers attributed the situation to the "soft" (high electron density) character of the copper center in the neutral Tp*Cu caused by the negative charged TP* ligand.
According to the theory of hard and soft acids and bases, the "soft" copper complex is difficult to coordinate with "hard" aliphatic amines, but prefers to coordinate with the "soft" sulfur atom of the chiral thiourea catalyst and thus enables the reaction.
Scientists said the study not only solves a long-standing challenge in enantioselective carbene insertion reactions. They added that it also provides a potentially general strategy for transition-metal-catalyzed asymmetric transformations, involving strongly coordinating substrates.
Eric N. Jacobson, a famous chemist at Harvard University, published a perspective article entitled "A catalytic one-two punch" in the same issue of Science journal, which systematically interpreted and highly praised the research.
"The cooperative action of achiral transition metal complexes with chiral hydrogen-bond donors holds enormous potential for achieving new asymmetric transformations," Jacobson said.
He emphasized that the combination of transition-metal catalyst and organocatalyst provided access to a wealth of reactivity modes inaccessible by either.
http://www.chinadaily.com.cn/edu/2019-11/26/content_37525586.htm
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