FREE-RADICAL THIOL-ENE AND THIOL-YNE COUPLINGS AS CLICK PROCESSES FOR GLYCOCONJUGATION - Click Chemistry in Glycoscience: New Developments and Strategies - page 57

FIGURE 3.5 Alkene functional dendrimer [G4]ene 48 47 prepared in the Hawker laboratory.

coupling [29, 30], we set out to develop an approach wherein concomitant TECs
between sugar thiols and the alkene groups of a preformed dendrimer would take
place in a single step [31]. In particular, as we planned to use the fourth genera-
tion alkene functional dendrimer [G4]ene 48 47 prepared in the Hawker laboratory
(Fig. 3.5) [32], the challenge laid in performing 48 regioselective and high-yielding
TECs on the same substrate. It was hoped that each reaction was nearly quantitative
because, for example, even a yield of 95% would give the multifunctionalized product
in only (0.95) 48 8.5% yield. Therefore, conditions were sought to avoid the for-

mation of undersubstituted byproducts that usually prove to be chromatographically
similar to the target compound. The first successful reaction was carried out using
dendrimer 47 and excess of 1-thio-

=

-D-glucose 44 (4 eq./ene) in DMF as the solvent
and under conditions of high substrate concentration (Scheme 3.15) [31]. After irradi-
ation of the mixture at max 365 nm for 1 h, 1 H NMR analysis revealed that all 48 ene

groups of 47 were consumed. Accordingly, the glycodendrimer 48a was obtained in
excellent isolated yield (94%). The robustness of TEC also in this program was