Carbohydrate-based dendrimers - Carbohydrate Chemistry: Chemical and Biological Approaches - page 258

(a) (b) (c)

Fig. 1 Carbohydrates in dendrimers: Carbohydrate-coated (a), carbohydrate-centered
(b) and carbohydrate-based (c).

categories: carbohydrate-coated, carbohydrate-centered and carbo-

hydrate-based dendrimer (Fig. 1).
In this paper we will focus more specifically on the third one, in which
the scaffold unit is originated from monosaccharides. Compare to classical
Pamam, Boltorn cores, carbohydrate units add much more 3D information
coded in the chirality in almost each carbon. The diversity of such structure
has been calculated for oligosaccharides and is very impressive, Laine 10
found over 1.05 10 12 possible branched hexasaccharides starting from a
basis set of 6 different sugars. Compared with a set of 6 different amino
acids, there is nearly 10 8 times less hexapeptides! Thereby the possible
structures of a carbohydrate-based dendrimers are tremendous and open a
large possible choice of scaffolds and thus properties. In addition, various
characteristics of such dendrimer can be easily controlled such as their
sizes, shapes, topologies, flexibilities and their surface properties.

2 Assembling full carbohydrate dendrimer by glycosylation
The glycosidic linkage seems to be the purest way for increasing
full-carbohydrate dendrimer generation. Direct glycosylation of every ad-
jacent hydroxyl of a carbohydrate is not practically possible, generally a two
or three carbons spacer is added. The first remarkable structure is the
''octopus'' glucoside made by Lindhorst et al. 11 This name referred to its
design: all the positions of the startingmonosaccharide aremodified and the
construction mimics the tentacles of the animal. The key synthetic steps
consist in a per-allylation and a subsequent per-hydroboration of a glucoside.
The following per-glycosylation was adapted to different structures such as a
trehalose and an allyl a- D -glucose. 12 SeeScheme1fortypicalreactions.
In the glycosylation step, a large excess of the donor, the benzoyl-
protected mannosyl trichloroacetimidate, and a high concentration of
TMSOTf in dichloromethane (DCM) or acetonitrile (ACN) were used, this
protocol avoid the formation of the orthoester byproduct. The different
structures were synthesized with good yields, from 64% up to 86%, for
the glycosylation and deprotection steps.
Thechoiceofthedonoriscriticalforthesuccessofthemultiglycosylation
step. For instance, Baker and coworkers 13 used a supposed more reactive
armed thioglycoside donor (instead of a trichloroacetimidate) in a very
similar octopus synthesis. Unfortunately, this glycosylation gave such low
yield compared to Lindhorst's method that the synthesis of the next

dendrimer generation will not be possible (Scheme 2).