Hansen Kasper H, Erichsen Andreas, Larsen Dennis, Beeren Sophie R
Department of Chemistry, Technical University of Denmark, Kemitorvet Building 207, Kongens Lyngby 2800, Denmark.
J Am Chem Soc. 2025 Apr 23;147(16):13851-13858. doi: 10.1021/jacs.5c02055. Epub 2025 Apr 9.
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, BCl, 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.
α-、β-和γ-环糊精（CDs）是由六个、七个和八个α-1,4-连接的D-吡喃葡萄糖单元形成的大环化合物，在工业上以吨级规模生产，用作食品、化妆品和药品中生物活性客体的宿主。含有超过八个葡萄糖单元的大环环糊精已为人所知数十年，但从未以超过毫克量的规模分离出来。我们报告了一种可扩展的方法，以高产率（>40%）、高纯度（无需色谱法纯度>95%）和前所未有的量（多克规模）合成由九个葡萄糖单元形成的δ-环糊精。我们利用一种超强离液十二硼酸盐模板BCl，从环糊精相互转化的酶介导动态组合库中指导δ-环糊精的选择性合成。我们的单步反应使用可回收模板、廉价的起始原料和商业“食品级”酶，因此能够获得大量的δ-环糊精。这项工作将首次大规模研究这种鲜为人知的较大环糊精的性质和应用。
