Development of α-Selective Glycosylation for the Synthesis of Deoxyfluorinated TN Antigen Analogues.

0541038 - ÚCHP 2022 RIV US eng J - Článek v odborném periodiku
Kurfiřt, Martin - Červenková Šťastná, Lucie - Cuřínová, Petra - Hamala, Vojtěch - Karban, Jindřich
Development of α-Selective Glycosylation for the Synthesis of Deoxyfluorinated TN Antigen Analogues.
Journal of Organic Chemistry. Roč. 86, č. 7 (2021), s. 5073-5090. ISSN 0022-3263. E-ISSN 1520-6904
Grant CEP: GA ČR(CZ) GA17-18203S
Institucionální podpora: RVO:67985858
Klíčová slova: amino acids * epitopes * stereochemistry
Obor OECD: Organic chemistry
Impakt faktor: 4.198, rok: 2021
Způsob publikování: Open access s časovým embargem

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.
Trvalý link: http://hdl.handle.net/11104/0318603