Peptide-Based Drug Design

202 Cudic and Burstein
chloride, sulfuric acid, trifluoroacetic anhydride, perchloric acid, or an acidic
ion-exchange resin. The complete acetylation of nonreducing sugars can be
effected by any method. In the case of a reducing sugar, the anomeric configuration
obtained depends on the catalyst used in acetylation and the temperature.
Acetylation of �-d- or�-d-glucopyranose with acetic anhydride and pyridine
at 0 ◦ C occurs without appreciable anomerization. The formation of the acetylated
�-d-anomer is favored at higher temperatures with sodium acetate as a
catalyst.
6. This step is recommended since �-anomer can be converted to �-anomer.
7. When anomeric acetate moiety is GlcNAc it is desirable to protect the N-acetyl
group (100).
8. Both of the anomeric glycosyl trichloroacetimidates can be obtained in pure
form, depending on the base (NaH, K2CO3, or DBU) used for deprotonation of
the reducing sugar).
9. When using NaH, always filtrate the reaction mixture over the Celite before the
evaporation step.
10. The high reactivity of glycosyl trichloroacetimidate can lead to side reactions
or even decomposition of the donor before reaction with the acceptor. To
improve yield and the stereocontrol of the reaction, the so-called inverse
glycosylation procedure is often used. In this case the glycosyl acceptor and
the catalyst are dissolved together followed by the addition of the glycosyl
donor.
11. The amount of Lewis acid employed varies from case to case. In many cases a
few drops of diluted solution of TMSOTf is sufficient to complete the reaction, in
other cases repeated additions of the catalyst are required. This might be particularly
necessary when orthoesters, formed as intermediates, are to be isomerized
to the respective glycosides.
12. Methyl triflate is volatile and extremely toxic; therefore the use of DMTST
is recommended. Other promotes such as N-iodosuccinimide (NIS) can be
used.
13. The use of Pd/C (87,89), neutral Raney Ni (W-2) (91,95), and Lyndlar’s catalyst
(90) have been reported in literature. Conditions used for the reduction of
glycosyl azide have to be carefully optimized in order to suppress anomerization
and the formation of undesired �-glycosides. Use of basic conditions
and procedures that avoid noble metals leads to decreased �-glycosides
formation (94).
14. Temperature and time of reaction may vary, as well as the final yields.
15. Glycosyl amines are not very stable; therefore the water bath temperature should
not exceed 30 ◦ C. Always prepare them freshly before further conversion to
glycopeptides.
16. The attempts to separate the starting reducing sugars from the glycosyl amines
by using Amberlit 15 (H + ) ion-exchange resin was not successful with all sugars
(96,97).
17. DCC and DIC are known allergens and should be handled with care.