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Selective synthesis rules uncovered

Posted on 1 September 2016

York chemists uncover rules for the selective synthesis of medicinally important structures.

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Many natural molecules with promising biological activity contain structural units in which functional groups can be arranged in one of two possible ways. One of the challenges in synthesising these molecules is to control this arrangement of functional groups relative to each other; as oftentimes current methods lead to mixtures of both possible arrangements.

This lack of control can be likened to the molecules in the reaction coming to a fork in the road. Some molecules take the left fork and have one arrangement of atoms (trans), while others take the right fork which gives a different arrangement (cis). The challenge is to make sure all the molecules go the same way, so that only one of the possible arrangement of atoms results. The Clarke group in the Chemistry Department at the University of York has discovered a method to direct the reaction down only one of these paths, leading to a large excess of one product.

The group used a combination of experimental and computational chemistry to understand the factors that control which reaction path the molecules take, and hence they have been able control the direction of the reaction. This has enabled them to devise a set of general rules to enable the selective synthesis of these molecules. The utility of the rules have been demonstrated as they have been applied to the synthesis of both diospongin A and B, natural products with anti-osteoporotic activity.

This research is published in Chemical Science 2016, DOI: 10.1039/C6SC03478K