Tumour-associated glycopeptide antigens and their modification in anticancer vaccines - Carbohydrate Chemistry: Chemical and Biological Approaches - page 511

Glycosylation of threonine ester 7 with 19 under azido-galactosylation
conditions 24 gave the fluorine containing Tn-antigen derivative 20 which
is convertible to the modified Tn antigen building block by treatment
with TFA. On the other hand, removal of the O-acetyl group by mild
transesterification 26 and regioselective galactosylation under Helferich
conditions 28,29 afforded the 6,6 0 -difluoro-substituted T-antigen threonine
building block.
Other fluorine containing tumour-associated antigen threonine
building blocks are accessible along similar routes. For example, 3-fluoro
galactosyl bromide 23 37 and selectively deprotected Tn antigen conju-
gate 28 reacted under Helferich conditions to furnish the 3 0 -fluoro-T-
antigen threonine ester 24, 38 which after de- and re-protection and
cleavage of the tert-butyl ester gave the 3 0 -fluoro-substituted building
block 35 25 useful for solid-phase syntheses.
2.3 C-linked glycosyl amino acids
Carbon-linked analogues of O-glycosylated amino acids 39,40 and peptides
received interest, because they are expected to mimic the natural
O-glycosides, but are more resistant to glycosidases and chemical
degradation. A novel way to construct metabolically stable carbohydrate
amino acid conjugates takes advantage from mild syntheses of exo-glycals
from glyconolactons. 41 This process carried out as a microwave-assisted
Petasis olefination 42 provides access to exo-glycals of different structure
including such ones derived from disaccharides, as for example 26. 43
When this exo-glycal derived from lactose was subjected to hydroboration
with 9-bora-bicyclononane (9-BBN), a highly stereoselective formation of
the b-C-glycosyl derivative 27 took place. The just formed C-glycosyl
methylboranes of this type are susceptible to an ecient C-alkyl-Suzuki
coupling with b-bromodehydroalanine or 4-iodotyrosine derivatives, as for
example 28,togiveC-glycosyl amino acid derivatives, e.g. 29 43 (Scheme 4).
The obtained C-lactosyl tyrosine derivative 29 was further transformed
by hydrogenolytic removal of the benzyl groups, O-acetylation, acidolytic
cleavage of the Boc and tert-butyl ester groups and selective introduction
Scheme 4 a) 9-BBN, THF; b) PdCl 2 (dppt), CH 2 Cl 2 , DMF, H 2 O, K 2 CO 3 ; c) i Pd/C H 2 ;ii
Ac 2 O, pyridine; iii TFA, iv Fmoc-OSu.