Note Cyclodextrins selectively modified on both rims using an O-3-debenzylative post-functionalisation, a consequence of the Sorrento meeting Maxime Guitet a , Ségolène Adam de Beaumais a , Yves Blériot b , Boris Vauzeilles c , Yongmin Zhang a , Mickaël Ménand a , Matthieu Sollogoub a,⇑ a UPMC Univ Paris 06, Institut Universitaire de France, Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), FR 2769, C. 181, 4 Place Jussieu, 75005 Paris, France b Université de Poitiers, UMR 6514, Laboratoire ‘Synthèse et Réactivité des Substances Naturelles’, 4, Avenue Michel Brunet 86022 Poitiers, France c CNRS and Univ Paris-Sud, Glycochimie Moléculaire et Macromoléculaire, ICMMO, UMR 8182, Orsay F-91405, France article info Article history: Received 3 November 2011 Received in revised form 28 November 2011 Accepted 2 December 2011 Available online 13 December 2011 Keywords: Cyclodextrin Deprotection Regioselective Chemoselective Post-functionalisation abstract A de-O-benzylation reaction induced by I 2 –Et 3 SiH and developed by Iadonisi et al. on mono- and disac- charides was applied to per- or polybenzylated a-cyclodextrins to furnish compounds deprotected at position 3 of all sugar units. This methodology allows the straightforward post-functionalisation of the secondary rim of cyclodextrins already functionalised on their primary rim. Ó 2011 Elsevier Ltd. All rights reserved. Regioselective access to a specific hydroxyl group is a central chemical challenge in carbohydrate research. Selective protection is a well-established strategy 1 with recent spectacular advances such as one pot access to any free hydroxyl group of a monosaccha- ride. 2 A reverse approach consists in regioselective deprotection of partially or fully protected sugars. 3 We have contributed to that field uncovering the ability of iso-butyl aluminium derivatives to regiose- lectively debenzylate perbenzylated sugars. 4 Understanding the mechanism of the reaction at the monosaccharide level and its extension to cyclodextrins (CDs) 5 allowed us to build-up on this reaction to introduce one, 5,6 two 7 or three 8 functionalities on the pri- mary rim of CD in a completely regioselective manner. This new abil- ity opened new possibilities in the field of biomaterials 9 and catalysis 10 as presented at the 16th Eurocarb. In addition, the Sorr- ento meeting   also drew our attention to recently published work by Iadonisi et al. dealing with selective debenzylations of poly-O-ben- zylated mono- and disaccharides using a combination of Et 3 SiH and I 2 . 11 One feature of this reaction is the absence of 6-O-debenzylation, preferentially leading to O-3 or O-4-debenzylated pyranosides, while the aluminium-based deprotections mainly produce O-2 and O-6- debenzylated products. More specifically, a perbenzylated maltose derivative undergoes a O-3-debenzylation using I 2 –Et 3 SiH. Returning from the congress, we logically wondered what would be the outcome of this reaction on polybenzylated CDs, expecting a similar regioselectivity. Perbenzylated CD 1 was hence submitted to the action of Et 3 SiH and I 2 (6.6 equiv) for 30 min from 60 to 35 °C and afforded compound 2 in a 58% yield (Scheme 1). Mass spectrometry (ESIMS) indicated the removal of six benzyl groups and 1 H NMR spectros- copy showed a single set of glucosidic signals characteristic of the C 6 symmetrical compound 2. The cleavage of all benzyl groups at po- sition 3 of the glucose units was further confirmed by COSY NMR experiment displaying cross peak between OH and H-3 (Fig. 1). Hence, I 2 –Et 3 SiH gives an efficient access to positions 3 through deprotection of perbenzylated a-CD 1. Usual access to these hydro- xyl groups consists of selective protection of 2- and 6-OHs. 12 If compatible with already primary-rim-functionalised CDs, this methodology could constitute a new post-functionalisation ap- proach in the challenging task of simultaneous and regioselective access to specific hydroxyl groups on both rims of the CD. 13 We therefore wondered if diol CD 3 5 and monoalcohol CD 4 8 both ob- tained through DIBAL-H deprotection of the perbenzylated CD 1 could undergo the deprotection reaction mediated by I 2 –Et 3 SiH. Similar conditions as those delineated for CD 1 applied on CDs 3 and 4 (6.6 equiv of I 2 and Et 3 SiH for 30 min to 1 h at 60 to 35 °C) afforded compounds 5 and 6 in 41% and 46% yields, respec- tively. The structures of both CDs 5 and 6 were confirmed to be hexa-de-O-benzylated by mass spectrometry (Scheme 2). 0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2011.12.002 ⇑ Corresponding author. Tel.: +44 1 44 27 61 63. E-mail address: matthieu.sollogoub@upmc.fr (M. Sollogoub).   16th European Carbohydrate Symposium, July 3–7, 2011, Sorrento, Naples, Italy. Carbohydrate Research 356 (2012) 278–281 Contents lists available at SciVerse ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres