Mikael Elofsson

Preparation of building blocks for glycopeptide synthesis by glycosylation of Fmoc amino acids having unprotected carboxyl groups

Abstract N α -Fmoc amino acids with an unprotected α-carboxyl group have been glycosylated with carbohydrate 1,2- trans peracetates using Lewis acids as promoters. Aliphatic and phenolic O - and S -glycosides of amino acids, with a 1,2- trans anomeric configuration, were obtained as products in 34–65% yields. The glycosylated building blocks have the protective groups of choice (i.e. O -acetyl and N α -Fmoc) for direct use in stepwise synthesis of glycopeptides. The starting materials are readily available and the method does not require an extensive experience in synthetic carbohydrate chemistry.

Preparation of Tn and sialyl Tn building blocks used in Fmoc solid-phase synthesis of glycopeptide fragments from HIV gp120

Abstract The synthesis of novel building blocks corresponding to the Tn [α-D-GalNAc-(1 → O)-Thr] an sialyl Tn [α-D-Neu5Ac-(2→6)-α-D-GalNAc-(1→O)-Thr] epitopes is descibed. The Tn building block was prepared from 4-methylphenyl 2-azido-2-deoxy-1-thio-β-D-galactopyranoside in four steps (42% yield) and carries tert-butyldimethylsilyl protective groups for the GalNAc moiety. Further conversion into a sialyl Tn building block, having acetyl protective groups for the sialic acid unit, was achieved in an additional four steps (37% yield). Both building blocks were used, in low excess (

Synthesis of Tn and sialyl Tn building blocks for solid phase glycopeptide synthesis

Abstract Tn (GalNAcα1→ O -Thr) and sialyl Tn (NeuAcα2→6GalNAcα1→ O -Thr) building blocks for direct use in Fmoc solid phase glycopeptide synthesis have been prepared in 3 and 5 steps, respectively, from p -cresyl 2-azido-2-deoxy-3,6-di- O-tert -butyldimethylsilyl-1-thio-β-D-galactopyranoside ( 3 ). The silyl protective groups used for the GalNAc moiety of the Tn building block may be removed simultaneously with glycopeptide cleavage from the solid phase under acidic conditions.

Building blocks for glycopeptide synthesis: Preparation of α-O-fucosylated fmoc serine and threonine in one step from L-fucose tetraacetate

Building blocks with O-acetylated fucose α-glycosidically linked to serine and threonine have been prepared (in 44 and 35% yields, respectively) by glycosylation of Fmoc-Ser/Thr-OH with L-fucose tetraacetate under boron trifluoride etherate promotion. Initially, the corresponding β-glycosides were formed as products but these rearranged to the more stable α-glycosides under the influence of the promoter.

Synthesis of a water-soluble serine-based neoglycolipid which can be covalently linked to solid phases

N alpha-Fmoc-serine pentafluorophenyl ester was glycosylated with perbenzoylated lactosyl bromide. The resulting product was coupled to a resin functionalized with 6-aminohexanoic acid and then N alpha-acylated to give a serine-based analogue of lactosylceramide. The water-soluble neoglycolipid was covalently linked to microtiter plates via its carboxyl group and was recognized by a lactose-binding lectin in an ELISA.

Preparation and structural characterization of N-glycated amino acid and linear or cyclic dipeptides containing the 6-amino-6-deoxy-1,2:3,4-di-O-isopropylidene-α--galactopyranose moiety

N-Glycated derivatives of glycine, glycylglycine, and 2,5-piperazinedione, containing the 6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactos-6-yl moiety, were synthesized and studied by X-ray crystallography and NMR spectroscopy. The crystal structures of N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactos-6-yl)glycine (2), its glycylglycine analogue (3), and 2,5-piperazinedione congener (4) were determined. The crystals of 2 are monoclinic; space group P21 with a = 10.5098(5), b = 5.7632(5), c = 13.0938(7) A, β = 90.245(5)°, Z = 2. The compounds 3 and 4 crystallized in the orthorhombic space group P212121 with a = 5.3429(9), b = 15.1484(4), c = 22.853(2) A, Z = 4 (3) and a = 28.69(6), b = 15.478(3), c = 15.504(2) A, Z = 4 (4). In the solid state the α-d-galactopyranose moiety of 2 and 3 existed in the twisted oT2 conformation, whereas in 4 a transition state between oT2 and oS2 was recorded. 1H NMR spectroscopy revealed that the conformation in solution for the galactopyranose moiety of compounds 2–4 closely resembled that found in the crystals.