C-linked 3- and 4-(glycosylacetylene)−Fmoc-phenylalanines were synthesized as rigid building
blocks for synthesis of libraries of neoglycopeptide templates. Perbenzylated 1,5-galactonolactone,
1,5- gluconolactone, and 1,5-mannonolactone were reacted with cerium TMS−acetylide and the
products reduced to the C-glycosylacetylene−TMS derivatives. The gluco and galacto configurations
yielded exclusively the β-C-glycoside, whereas the mannonolactone gave a mixture of α-C- and
β-C-anomer. The products were subjected to acetolysis and TMS cleavage. The resulting peracetylated glycosylacetylenes were cross-coupled with the (R,S)-N
α-acetyl-3- and 4-iodophenylalanine
O-methyl esters by Pd(0) catalysis in piperidine to give the eight possible C-linked glycosyl amino
acid building blocks 33−40 as diastereomeric pairs. These were O-deacetylated. As an example of
further conversion into neoglycopeptide templates the N-acetyl group of the 4-linked galacto-diastereomeric pair 43 was hydrolyzed selectively by acylase 1 and separated from the (R)-stereoisomer. The product was converted to 4-(β-C-galactosylacetylene)(N
α-Fmoc-)-l-phenylalanine
(52) by reaction with Fmoc−OSu. Acid hydrolysis of galactosyl acetylene phenyl alanine 43 at
elevated temperature afforded the conversion of the acetylene to the 1‘-oxo derivative which was
also N
α-Fmoc protected. The building blocks were used in the glycopeptide synthesis of three
neoglycopeptide templates 54, 55, and 56 known to bind to murine MHC class II Ek and to present
the glycan for interaction with the T-cell receptor. This template has previously been employed to
elicit a carbohydrate specific T-cell response.
Synthesis and Biological Activity of a New Anti-Factor Xa Pentasaccharide with a C-Interglycosidic Bond.--(HELMBOLDT, A.; PETITOU, M.; MALLET, J.-M.; HERAULT, J.-P.; LORMEAU, J.-C.; DRIGUEZ, P. A.; HERBERT, J.-M.; SINAY, P.; Bioorg. Med.
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