Novel Type of Rigid C-Linked Glycosylacetylene−Phenylalanine Building Blocks for Combinatorial Synthesis of C-linked Glycopeptides

Abstract

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.

Design of Triazole‐Tethered Glycoclusters Exhibiting Three Different Spatial Arrangements and Comparative Study of their Affinities towards PA‐IL and RCA 120 by Using a DNA‐Based Glycoarray

“…[24,25] Accordingly, 8 was allowed to react with a stoichiometric amount (4.0 equiv) of the known [30] ethynyl tetra-O-acetyl-b-d-C-galactopyranoside 9 in the presence of Cu I and Hünig's base to give the triazole-tethered tetravalent glycosylated calix [4]arene, 10. Quite remarkably, the four click reactions on the same substrate 8 must all have occurred quite efficiently, because compound 10 was obtained in 75 % yield, corresponding to a 93 % average yield for each cycloaddition reaction.…”

Regioselectivity of Larock Indole Synthesis Using Functionalized Alkynes

“…On the other hand, preparation of unprotected glucosylacetylene 19 from 18 by debenzylation proved difficult. 19) Since all attempted deprotection of 18 were unsuccessful, we explored an alternative route for unprotected sugar acetylene 19.…”

“…(-D-Glucopyranosyl)but-1-yne (19) and (-D-gulopyranosyl)but-1-yne (27). A solution of a mixture of 25 and 26 (157 mg) in MeOH (2.5 ml), Et 3 N (0.5 ml), and H 2 O (0.5 ml) was stirred at room temperature for 12 h, and then concentrated azeotropically with toluene.…”

Synthesis of Sugar‐Based Silica Gels by Copper‐Catalysed Azide–Alkyne Cycloaddition via a Single‐Step Azido‐Activated Silica Intermediate and the Use of the Gels in Hydrophilic Interaction Chromatography

“…Compound 1 was obtained by the transesterification of ethynyl tetra-O-acetyl-C-galactoside (NaOMe, MeOH, RT, 4 h, 95 % yield), prepared as previously reported. [24] It is worth noting that sugar 1 was used to establish a chemically stable carbon-carbon bond at the anomeric position in the final glycosylated material.…”