Synthesis of a Serine-Based Neuraminic Acid C -Glycoside (original) (raw)
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N-Alkylated C-Glycosyl Amino Acid Derivatives: Synthesis by a One-Pot Four-Component Ugi Reaction
ChemPlusChem, 2020
C-glycosides represent an important group of naturally occurring glycosylation derivatives but are also efficient mimetics of native O-glycosides. Here, a one-pot four-component methodology is described toward a library of N-alkylated C-glycosyl amino acid derivatives comprising seven different isopropylidene-protected carbohydrate units. The applied methodology tolerates different amines and isocyanides and provides access to Ugi products in yields up to 85 %. X-ray analysis of selected products bearing three different carbohydrate motifs and comparison of their crystal structures with similar ones deposited in Cambridge Crystallographic Database revealed that four structures adopt different conformations, mostly not typical for peptide structures. This property opens the possibility to exploit here described N-alkylated C-glycosyl amino acid derivatives as templates to access different biotic and abiotic secondary structures.
Stereoselective synthesis of O-serinyl/threoninyl-2-acetamido-2-deoxy-a- or �-glycosides
Carbohyd Res, 1995
General glycosidation methodology has been developed which can selectively provide 2acetamido-2-deoxy-a-or /3-glycosides of fl-hydroxy-a-amino acid derivatives [glucopyranoside-(8, 43), galactopyranoside-(9, 13), mannopyranoside-(10), lactoside analogs (11, 38) and 3-O-/3-galactopyranosyl-mannopyranoside (12)] stereoselectively in excellent yield from the highly nucleophilic a-imino esters (Schiff bases) of L-serine and L-threonine. Various glycosides were converted via their amino and acetamido derivatives to Fmoc-protected serinyl-or threoninyl-glycosides (24-28, 37, 41, 46) which are all suitable building blocks for the solid-phase synthesis of O-glycopeptides. Complete 1H-and 13C-NMR data are provided for all compounds.
A novel glycosyl donor for synthesis of 2-acetamido-4-amino-2,4,6-trideoxy-a- d-galactopyranosides
Carbohyd Res, 2010
2-Azido-4-benzylamino-4-N-,3-O-carbonyl-2,4,6-trideoxy-D-galactopyranosyl trichloroacetimidate (14) was conveniently prepared in six steps by regioselective introduction of an N-benzyl carbamate at O-3 of 6-deoxy-D-glucal 6, followed by mesylation at O-4. Intramolecular displacement of the leaving group afforded oxazolidinone 11. Azidonitration of the bicyclic glycal 11 gave the glycosyl nitrate anomers 12 in good yield and stereoselectivity. Hydrolysis of the anomeric nitrates under aqueous conditions gave the pyranose 13, which was easily converted into the imidate 14. Glycosylation of cyclohexanol by 14 gave glycosides 16a and 16b in a ratio of 4:1.
Carbohydrate Research, 1982
of methyl .%acetamido-4,7,8,9-tetra-%acetyl-2-chloro-2,3,5trideoxy-/2-D-gZ~cero-D-g~Z~c?~-2-nonulop~anosonate with benzyl 2,3,4-tri-O-benzylj?-D-galactopyranoside, using silver salicylate as promoter, gave benzyl 2,3,4&-i-0benzyl-6-O-(methyl 5-acetamido-4,7,S,9-tetra-O-acetyl-3,5-dideoxy-a-D-gZ~cero-D-ga-Zacto-2-nonulopyranosylonate)-B_D-galactop~~oside (11) as the main product in 65 % yield. Furthermore, the following by-products were formed: methyl 5-acetamido-4,7,8,9-tetra-O-acety1-3,5-dideoxy-2-O-s~icyioyl-D-gZ~cero-D-gaZacto-2-nonuIopyranosonate, methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-g~cero-D-galacto-non-%enopyranosonate, and an impure compound that gave, after O-deacetylation and catalytic hydrogenolysis, 6-@(methyl 5-acetamido-3,5-dideoxy-B-D-gZ~cero-D-gaZacto-2-nonulopyranosylonate)-D-g~actose.
Carbohydrate Research, 2015
intermediates which give access to three C-glycoside representatives (7-9), as well as access to the racemic mixture of the nonisomerisable homologue of b-2-deoxy glucose 6-phosphate, 10. 2. Results and discussion 2.1. Synthesis of tiazofurin pyranosyl C-nucleoside 7 There are three classical routes to C-nucleosides and C-pyranosides. The first approach involves a direct attachment of a preformed nucleophilic aglycon to a protected carbohydrate moiety. This chemistry includes the reaction of heterocyclic organometallic compounds with pyranosyl 31,32 or furanosyl halides, 33 1,2-anhydro-furanoses or-pyranoses, 34 functionalised lactones 35 and Heck-type coupling onto glycal moieties. 36-41 The second most common methodology consists in building-up the sugar moiety upon an aglycon unit and includes the tandem ene-IMSC sequence. This latter approach allows the introduction, in some cases, of up to four stereogenic centres in a one-step synthesis. 26,42 Finally, the last strategy consists of introducing a functional group at the anomeric position of the sugar derivative with the subsequent building-up of the aromatic moiety. 43 This typically involves the stereoselective introduction of a nitrile or alkyne group at the anomeric position followed by a cycloaddition reaction to build-up the heterocyclic base and generate the C-nucleoside or C-glycoside. We seek to increase the scope of the two latter methodologies by combining the diastereoselective control we have optimised for the (D/L)-C-nucleoside syntheses using the tandem ene-IMSC sequence with the use of a functionalisable substituent at the C-1 position. Key to a successful implementation of the tandem ene-IMSC sequence is the oxidative cleavage of the exo-alkene functionality, for example, compound 14, generated upon cyclisation and the reduction of the resulting carbonyl. Firstly, we wished to determine if the tandem ene-IMSC sequence was suitable for the preparation of C-glycosides that incorporate electron rich heteroaryl moieties, such as compound 7. Although it was possible to access the diastereomerically pure exo-methylene heteroaromatic pyran 14 (Scheme 2) from thiazolylaldehyde 11, yields remained very low. Crucially, the oxidative cleavage of the exo-alkene 14 also proved problematic due to the presence of the oxidatively sensitive thiazolyl ring, which remained unstable to most oxidative cleavage conditions, ranging from ozonolysis to epoxidation/oxidation and cis-diol oxidations.
Carbohydrate Research, 1983
A facile synthesis of p-nitrophenyl 2-acetamido-2-deoxy-4-O-P_D-galactopyranosyl-P-D-glucopyranoside was accomplished by saponification of the product obtained by reaction of 2-acetamido-3,6-di-O-acetyl-2-deoxy-4-0-(2,3,4,6-tetra-O-acetyl-/I-D-galactopyranosyl)-aD -glucopyranosyl chloride and Amberlyst A-26 p-nitrophenoxide. The reaction ofp-nitrophenyl2,3-O-isopropylidene-cc-D-mannopyranoside (7) with the easily accessible 2-methyl-[4,6-di-O-acetyl-2-deoxy-3-0-(2,3,4,6-tetra-Oacetyl-~-o-galactopyranosyl)-a-o-glucopyrano]-[2,1-d]-2-oxazoline proceeded readily, to give the protected trisaccharide derivative which, on deacetonation, followed by 0-deacetylation, produced one of the title trisaccharides, namely, p-nitrophenyl 6-0-(2-acetamido-2-deoxy-3-O-P-D-galactopyranosyl-~-D-glucopyranosyl)-a-~-mannopyranoside. Synthesis of the other trisaccharide, p-nitrophenyl 6-0-(2-acetamido-2-deoxy-4-0-/3-D-galactopyranosyl-~-D-glucopyranosyl)-c(-Dmannopyranoside was accomplished by a similar reaction-sequence when the corresponding 2-methyl-[3,6di-O-acetyl-2-deoxy-4-0-(2,3,4,6-tetra-O-acetyl-~-n-galactopyranosyl)-aD -glucopyrano]-[2,1-d]-2-oxazoline (19) reacted with 7. Preparation of oxazoline 19 was achieved via acetolysis of methyl 2-acetamido-2-deoxy-4-O-B-D-galactopyranosyl-~-Dglucopyranoside. The structures assigned to the final saccharides were supported by 'H-and i3C-n.m.r.-spectral data. *Synthetic Studies in Carbohydrates, Part XXIX. For Part XXVIII, see ref. 1. **To whom correspondence should be directed.
Carbohydrate Research, 2002
The spacer-armed trisaccharide, Neu5Gc-a-(2 3%)-lactosamine 3-aminopropyl glycoside, was synthesized by regio-and stereoselective sialylation of the suitably protected triol acceptor, 3-trifluoroacetamidopropyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(6-O-benzyl-b-D-galactopyranosyl)-b-D-glucopyranoside, with the donor methyl [phenyl 5-acetoxyacetamido-4,7,8,9tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-a,b-D-galacto-2-nonulopyranosid]onate. The donor was obtained, in turn, from methyl [phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-a,b-D-galacto-2-nonulopyranosid]onate by N-tertbutoxycarbonylation of the acetamido group followed by total N-and O-deacetylation, per-O-acetylation, subsequent Boc group removal, and N-acetoxyacetylation.
Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives
2020
N-acetyl neuraminic acid (Neu5Ac) is a densely functionalized nine-carbon monosaccharide. It ubiquitously decorates the surface of mammalian cells were it is found in terminal positions of glycolipids and glycoproteins. This important saccharide and natural analogs play important roles in a number of processes in health and disease. Despite this few Neu5Ac based therapeutics have been developed. To further study and understand the chemistry and biology of Neu5Ac efficient protocols for synthesis of the parent natural compounds as well as synthetic analogs are required. In the manuscript, we report investigation of alkylation reactions to produce selectively modified Neu5Ac with focus on position 4. The study provides insights in the reaction and we establish robust protocols that allow selective modification of Neu5Ac for use as tool compounds and starting points for drug discovery.
Preparative routes to methyl 2-acetamido-2,6-dideoxy-α-d-glucopyranoside
Carbohydrate Research, 1983
2-Amino-2,6-dideoxy-D-glucose (quinovosamine) is a component residue' of the O-chain polysaccharide in the lipopolysaccharide antigens' of Pseudomonas aeruginosa, Fisher immunotypes 3,4, and 5. In connection with synthesis of artificial antigens and immunoadsorbents based on oligosaccharide segments3 of the Ochains, a convenient preparative route to quinovosamine was of interest. This amino sugar has been synthesized from derivatives of 2-amino-2-deoxy-D-glucose by way of selective 6-O-monosulfonylation4~s, and subsequently obtained by several other route&'; a preparative route employed in this laboratory' was based on N-bromosuccinimide-mediated ring-opening of a 4,6-benzylidene acetal'. The objective of the present work was to improve the net yield in preparation of the title glycoside from 2-amino-2-deoxy-D-glucose. This was accomplished in two routes, one a modification of the methods based on the 4,6_benzylidene acetal, and the second, judged superior overall, on selective C-6 monobromination by the action of carbon tetrabromide-triphenylphosphine'. Concurrently, Anderson and coworkers lo have prepared the title glycoside, having physical constants in good agreement with those reported here, by a C-6 monobromination step employing Nbromosuccinimide-triphenylphosphine"; their report is published simultaneously with this one. Glycosidation of 2-acetamido-2-deoxy-D-glucose with methanol in the presence of cation-exchange resin'*" gave, in 91% yield, methyl 2-acetamido-2-deoxy-a&D-glucopyranoside (1) as a cocrystallized, 5: 1 cu,/3 mixture, [LY],, t-98", and this was treated in pyridine at 6@-65" with 2 equivalents of triphenylphosphine and 1 equivalent of carbon tetrabromide to give, in 46% yield, crystalline methyl 2acetamido-6-bromo-2,6-dideoxy-cY-D-glucopyranoside (2). Hydrogenolysis of the bromide 2 in the presence of Raney nickel gave crystalline methyl 2-acetamido-2,6dideoxy-aD -glucopyranoside (3) in essentially quantitative yield. Recrystallized from isopropyl alcohol, compound 3 had a m.p. in agreement with the litera-*Supported, in part, by NIH Grant No. GM-20181.