A new approach to A,B-difunctionalisation of cyclodextrins using bulky 1,3-bis[bis(aryl)chloromethyl]benzenes as capping reagents

Abstract

1,3-Bis[bis(4-tert-butylphenyl)chloromethyl]benzene and 1,3-bis[bis(4-anisyl)chloromethyl]benzene were employed as regioselective capping reagents for the preparation of C-6A,C-6B-bridged, permethylated alpha- and beta-CD derivatives; isolated yields up to 55% of proximally capped, methylated CDs were obtained, thus opening the way to the straightforward preparation of a wide range of A,B-functionalised CDs. As revealed by a single crystal X-ray diffraction study, the benzene-1,3-bis[bis(4-tert-butylphenyl)methyl] spacer is perfectly suited for A,B-capping of beta-cyclodextrin.

Regioselective Double Capping of Cyclodextrin Scaffolds

“…It is worth mentioning here that the aromatic region of the 1 H NMR spectrum of 3 bears strong resemblance to the singly capped-CD 2. [21] In particular, two low-field signals for the H a and H a protons of the central aromatic rings of the "bis-trityl" fragments at d = 7.61 and 7.72 ppm, respectively, are typical of non-dangling 6 A ,6…”

“…[ 21] We anticipated that the use of two equivalents of 1 for the first alkylation step would regioselectively lead to an A,B:D,E doubly capped b-CD, as a result of both the capacity of the difunctional reagent to strap adjacent glucose units and the Abstract: Four different regioselective double capping reactions were applied either to a-or b-cyclodextrin (CD) scaffolds. The first, which relied on the use of a rigid, bulky dialkylating reagent containing two trityl-like subunits, gave access to an A,B,D,E-tetrafunctionalised b-CD regioisomer in large scale reactions.…”

“…All commercial reagents were used as supplied. [21] and dimesylate 11 [32] were synthesised according to literature procedures.…”

Chemical Clockwise Tridifferentiation of α‐ and β‐Cyclodextrins: Bascule‐Bridge or Deoxy‐Sugars Strategies

“…Keywords: aluminum · concave molecules · cyclodextrins · oligosaccharides · regioselectivity agents. [7,8] When one wants to go one step further and introduce a second functional group different from the first one in order to get a tridifferentiated cycle (Scheme 1) the same problems are encountered, with even more possible regioisomers formed. For the sake of clarity, we wish to define these terms.…”

“…[13] A remarkable feature of this reaction is that it is a rare example of selective CD bis-functionalisation being as efficient on a-and bCDs. [8] As an illustration of our previous assumption on the link between easy functionalisation and access to novel artificial enzymes, M. Bols et al nicely used this methodology to build up a series of efficient artificial enzymes. [14] We would now like to give the full account of the duplication of this process that allows the tridifferentiation of the upper rim of a-and b-CDs.…”