The synthesis and conformational properties of the diastereoisomeric βDGal(1→4)βDGlcNAc(1→6)6-C-CH₃-D-Gal trisaccharides

Abstract

. Can. J. Chem. 60, 81 (1982).The trisaccharide P~Gal(l-.4)~~GlcNAc(1-.6)~Gal was known to be bound strongly by the so-called anti-I Ma monoclonal antibody. In order to help assess the conformation about the 1+6 glycosidic linkage that is accepted by the antibody combining site, the conformationally well-defined PDGal(l+4)PDGlcNAc(l+6) derivatives of 7-deoxy-L-glycero-D-galacto-heptopyranose and 7-deoxy-D-glycero-D-galacto-heptopyranose were synthesized. The conformational preferences for these trisaccharides were established by 'H nmr spectroscopy and rationalized by computer-assisted molecular modelling. Introduction past (2), the hydroxyl group hydrogen atoms were The myeloma protein which was classified (1) as neglected and the h~d r o x~m e t h~l groups of the the monoclonal antibody I Ma (group 1) was found h e x o~e units, when present, were treated as 6-deoxy to possess a combining site which binds at the units. The parameters for the PDG~cNAc unit were surface of a P~Gal(l--+4)P~GlcNAc(l+6) struc-derived from the X-ray structures of 4-N-(2-acetural unit which was common to a number of the tamido-2-deox~-P-~-gluco~~ranos~l)-~-as~aragine oligosacchardies studied.(4) and lactose (5). The coordinates for the hydroWe have predicted (2) that the conformational gen atoms attached to carbon were established by preference for the glycosidic linkage at the 4-position fixing the C-H bond length at

Synthesis and Biological Evaluation of 6-[(1R)-1-Hydroxyethyl]-2,4a(R),6(S),8a(R)-tetrahydropyrano-[3,2-b]-pyran-2-one and Structural Analogues of the Putative Structure of Diplopyrone

“… This oxidation was also carried out using a polymer-bound reagent, which gave improved yields on smaller (1–2 mmol) scales, but turned out to be less desirable for scaled-up preparations of 13 . The addition of organometallic reagents to aldehyde 13 has provided products that have found use as building blocks for trisaccharides used to study monoclonal antibodies, enzyme inhibitors, and higher-carbon sugars . However, most of the addition reactions of organometallic reagents to 13 provide mixtures of diastereomers with the highest selectivity for 14 on the order of 2.5:1 to 3.0:1 .…”

“…In the larger-scale preparation included in the experimental section of this paper, the minor isomer was estimated at 0.7%. The structure of 14 was assigned based on comparison of NMR data with that published by Lemieux . Further confirmation of the structure of 14 was provided by X-ray analysis of the corresponding p -bromobenzoate, which shows that the configuration at the newly formed C-9 chirality center is R .…”

“…The addition of organometallic reagents to aldehyde 13 has provided products that Scheme 2. Synthesis of Pyranopyran Nitrile 4 have found use as building blocks for trisaccharides used to study monoclonal antibodies, 33 enzyme inhibitors, 34 and higher-carbon sugars. 17 However, most of the addition reactions of organometallic reagents to 13 provide mixtures of diastereomers with the highest selectivity for 14 on the order of 2.5:1 to 3.0:1.…”

“…The structure of 14 was assigned based on comparison of NMR data with that published by Lemieux. 33 Further confirmation of the structure of 14 was provided by X-ray analysis of the corresponding p-bromobenzoate, which shows that the configuration at the newly formed C-9 chirality center is R. 42 The yield and stereoselectivity of the methyltitaniumbased route to chain-extension were critical to the overall success of our synthesis. Two of the four chirality centers of pyranopyran 2, C-6 and C-9, are established in 14, without the production of diastereomers.…”

Crystal state and solution conformation of the B blood group trisaccharide α‐l‐Fucp‐(1→2)‐[α‐d‐Galp]‐(1→3)]‐β‐d‐Galp‐OCH3

“…1) is shown, by a suite of NMR techniques, to adopt a solution conformation very similar to that observed in the X‐ray crystal structure. The latter conformation is also well modeled by HSEA [31] and GEGOP [41] forcefields, simple empirical procedures that have consistently provided useful models of oligosaccharide conformational preferences, except when polar inter‐ residue interactions are present [42]. As no evidence for the existence of either direct or water‐mediated hydrogen bonds was found in the crystal structure, it is concluded that stereoelectronic and non‐bonding interactions are responsible for the conformational preference.…”