posted on 2021-03-11, 20:40authored byMartin Kurfiřt, Červenková
Št’astná Lucie, Petra Cuřínová, Vojtěch Hamala, Jindřich Karban
The Tn antigen (GalNAcα1-Thr/Ser)
is abundantly expressed
in many tumors but rarely found in healthy tissues, which makes it
an attractive epitope for antitumor immunotherapy. The use of the
Tn antigen in the development of therapeutic antitumor vaccines is
hampered by its low immunogenicity, which may be enhanced by deoxyfluorination
of the GalNAc moiety. Here, we report the synthesis of protected 3-
and 4-fluoro analogues of the threonine-containing Tn antigen. As
the stereoselective synthesis of α-linked fluorinated GalNAc
is difficult, we prepared a panel of C3 and C4 deoxyfluorinated galactosazide
thiodonors and evaluated their stereoselectivity in the glycosylation
of carbohydrate acceptors and threonine derivatives. Glycosylation
of threonine derivatives with O-benzylated C4 fluoro
donors gave only modest but usable α-selectivity of α/β
= 2.5–3/1. The use of acyl and silyl protection at the 3- and
6-positions of the C4 fluoro donors did not enhance the selectivity.
Installing a 4,6-di-tert-butylsilylene-protecting
group in C3 fluoro donors resulted in exclusive α-selectivity
and reaffirmed the strong α-directing effect of this protective
group in glycosylation with galacto-configured glycosyl donors.