Scientists have discovered a new way to synthesize chiral tetraarylmethanes

The research was published in the journal Catalysis naturur on 14 December 2020.

There has been a strong tendency toward serial molecules and disc formation in drug molecules. In contrast, spherical molecules were used at smaller intervals, due to the lack of effective access to the latter chemical space. In particular, effective strategies for synthesizing tetraarylmethanes, a specific family of spherical molecules, have remained scarce.

Spiral tetraarylmethanes (CTAMs), a specific family of spherical molecules containing four distinct aryl groups with marked stereochemistry, remain a mystery due to the lack of efficient asymmetric synthesis. The challenge in unbalanced synthesis of CTAMs lies not only on the high barrier in making the C-link? C densely linking the middle aryl and the aryl rings with conventional strategies, but also the problem in stereodifferentiation between the existing and similar aryl rings when attaching a new aryl ring to the carbon in the medium.

“The problem associated with the synthesis of chiral tetraarylmethanes is the need to overcome a large energy barrier in forming densely populated bonds around a small carbon atom,” Jianwei Sun said. lead researcher and Professor at the Department of Chemistry, HKUST. “The other problem is that the connection must be made in a marked 3D direction. Both of these requirements greatly reduce the chances of success, but we have been able to overcome it by using a tagging strategy. “

Starting from triarylmethanols with appropriate tags, the protocol exploits hydrogen bond interactions in the major para-quinone methide and indole iminium intermediates to construct two libraries of enantioenriched CTAMs.

“First, we hypothesized that a tribal triarylmethane with a carbon-leaving group in the center would be readily activated by a catalpa to generate the intermediate triarylmethyl cation,” the sun continued. “We put different tags on two of the three aryl groups. When a hydroxy group is attached to one of the aryl groups, the chiral ion pair could be made more stable as a quinone methide hydrogen-bond (QM The other tag then provides its secondary hydrogen bond interaction to provide the main difference. “

Spiral spherical molecules synthesized by this method have shown promising activity against cancer cells as well as enterovirus. The group plans to establish a large and diverse library of such spherical molecules for lead optimization and structural activity relationship analysis, which would eventually lead to collaboration opportunities with experience in pharmaceutical chemistry, biology chemical, viral biology, and physiology.

“High efficiency and selectivity is where our catalytic asymmetric approach shines,” Sun said. “We are excited to begin this study of a new paradigm of a neglected chemical space.”

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