Cyclodextrins (CDs), a class of cyclic oligosaccharides that were “born” in 1891, have opened up endless research and commercial opportunities in numerous fields that span carbohydrate, supramolecular (host-guest) and analytical chemistry all the way from research laboratories in academia to the mass production of products—e.g., skin care enablers to drug delivery systems—in industry. Although they have been known for over 130 years, the most accessible cyclic homologues are α-, β-, and γ-CDs, which contain six, seven, and eight D-glucopyranosyl units, respectively. The odyssey of naturally occurring CDs suggests that despite the number of CDs is rather limited, their reach has been limitless.

For a long time, scientists (chemists, biologists, medical scientists, etc) have been exploring novel methods to synthesise—both chemically and enzymatically—CD homologues. These efforts include the syntheses of unusual smaller analogues with only 3, 4, and 5 D-glucose units and the making of rare larger CDs with 9 to 12 D-glucose units. All the currently available CDs are composed solely of D-glucopyranosyl units as the monomers, while the syntheses of mirror-image CDs have remained an untouched goal of the CD community, limiting the realisation of their full potential, such as in the development of new supramolecular sensors and catalysts, chiral materials, as well as innovative drug delivery systems and active pharmaceutical ingredients.

In order to fulfil this fundamental research niche, a collaborative research team led by Professor Sir Fraser STODDART in the Department of Chemistry of The University of Hong Kong (HKU) and Professor Daniel ARMSTRONG in the Department of Chemistry and Biochemistry of The University of Texas at Arlington, recently developed a concise approach to link L-glucopyranosyl monosaccharides together in a highly diastereoselective and scalable manner, resulting in the production of circa half-gram quantities of α-, β-, and γ-L-CDs. The availability of L-CDs for the first time—ever since the serendipitous discovery of their natural counterparts back in 1891—has enabled the elucidation of an unprecedented chiral self-sorting of a racemic modification of β-CDs in the solid state and an investigation of the chiral recognition of enantiomeric guests by α-L-CD in water. The research work was recently published and featured on the Cover in a leading scientific journal – Nature Synthesis. A corresponding News & Views Article written by Professor Sophie BEEREN, a cyclodextrin expert working at Technical University of Denmark, was also published in the same Journal (https://www.nature.com/articles/s44160-024-00512-w).