Multiple homo- and hetero-functionalizations of alpha-cyclodextrin through oriented deprotections

Introduction of one or more functions on a cyclodextrin in a regioselective manner is a complex task. The discovery of a blueprint strategy involving regioselective deprotection reactions of fully protected cyclodextrins, instead of functionalization of native cyclodextrins, allowed us to propose an efficient alternative to reach this goal. In this paper, we have applied previously delineated strategies, based on steric decompression, to duplicate our deprotection reaction, using a combination of mono- or di-deprotections to access cyclodextrins with two, three and five points of attachment for one, two or three different new functions. The patterns of multi-functionalization delineated here are not accessible by any other methods. Indeed, it is the first time ever a cyclodextrin bearing four different groups is synthesized in a completely controlled manner. This work paves the way to the use of cyclodextrins as multi-functional macrocyclic scaffolds, a use they have long been meant for, but lack of reliable functionalization methods hindered this development.