Programmed synthesis of Hepta-Differentiated β-Cyclodextrin: 1 out of 117655 Arrangements

Cyclodextrin poly-functionalization has fueled progress in their use in multiple applications such as enzyme mimicry, but also in the polymer sciences, luminescence, as sensors or for biomedical applications. However, regioselective access to a given pattern of functions on beta-cyclodextrin is still very limited. We uncover a new orienting group, the thioacetate, that expands the toolbox available for cyclodextrin poly-hetero-functionalization using diisobutylaluminum hydride (DIBAL-H) promoted debenzylation. The usefulness of this group is illustrated in the first synthesis of a precisely hepta-hetero-functionalized beta-cyclodextrin. By way of comparison, a random hepta-functionalization would give 117655 different molecules. This synthesis is not simply the vain quest for the Holy Grail of CD hetero-functionalization, but it illustrates the versatility of the DIBAL-H oriented hetero-functionalization strategy, opening the way to a multitude of useful functionalization patterns for new practical applications.

Automated summary

The discovery of a new orienting group, thioacetate, in cyclodextrin poly-functionalization using DIBAL-H promoted debenzylation has enabled the synthesis of a precisely hepta-hetero-functionalized beta-cyclodextrin, showcasing the versatility of this oriented hetero-functionalization strategy for new practical applications.