Enzyme-Mediated Dynamic Combinatorial Chemistry Enables Large-Scale Synthesis of δ-Cyclodextrin

α-, β-, and γ-cyclodextrins (CDs) are macrocycles formed from six, seven, and eight α-1,4-linked d-glucopyranose units and are industrially produced on ton scales for use as hosts for bioactive guests in foods, cosmetics, and pharmaceuticals. Large-ring cyclodextrins, with more than eight glucose units, have been known for decades but never isolated in more than milligram quantities. We report a scalable method to synthesize δ-CD, formed from nine glucose units, in high yield (>40%), high purity (>95% purity without chromatography), and unprecedented quantities (multigram scale). We exploit a superchaotropic dodecaborate template, B₁₂Cl₁₂^2-, to direct the selective synthesis of δ-CD from within an enzyme-mediated dynamic combinatorial library of interconverting cyclodextrins. Our single-step reaction uses a recyclable template, cheap starting materials, and a commercial 'food-grade' enzyme and can thus give access to large quantities of δ-CD. This work will enable the first large-scale investigations of the properties and applications of this little-known larger CD.