New Effective Synthesis of (N-Acetyl- and N-Stearoyl-2-amino-2-deoxy-β-D-glucopyranosyl)-(1→4)-N-acetylnormuramoyl-L-2-aminobutanoyl-D-isoglutamine, Analogs of GMDP with Immunopotentiating Activity

Ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (5), prepared by benzylation of ethyl 2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (4), was transformed by reaction with bromine into 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide (6). Thioglycoside 5 in the presence of methyl triflate and glycosylbromide 6 in the presence of silver triflate were used as glycosyl donors for condensation with benzyl 2-acetamido-3-O-allyl-6-O-benzyl-2-deoxy-α-D-glucopyranoside (7), to give benzyl 2-acetamido-3-O-allyl-6-O-benzyl-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-2-deoxy-α-D-glucopyranoside (8). Its reductive dephthaloylation with NaBH4/AcOH afforded benzyl 2-acetamido-3-O-allyl-4-O-(2-amino-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)- 6-O-benzyl-2-deoxy-α-D-glucopyranoside (11). Compound 11 was N-acylated to give benzyl 2-acetamido-4-O-(2-acylamino-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)-3-O-allyl-6-O-benzyl-2-deoxy-α-D-glucopyranosides (12a) or (12b). These compounds were converted into corresponding benzyl 2-acetamido-4-O-(2-acylamino-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)-6-O-benzyl-3-O-carboxymethyl-2-deoxy-α-D-glucopyranosides which, by condensation with H-L-Abu-D-isoGln(OBzl) followed by hydrogenolysis of protective benzyl groups, furnished glycopeptides 16a and 16b. Intramolecular O→N migration of the allyl protecting group followed by its reduction to the propyl residue by reaction of compound 8 with hydrazine or hydrazinium acetate, to give benzyl 2-acetamido-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-propylamino-β-D-glucopyranosyl)-6-O-benzyl-2-deoxy-α-D-glucopyranoside (9), is also described.

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Effective Synthesis of Nucleosides Utilizing O-Acetyl-Glycosyl Chlorides as Glycosyl Donors in the Absence of Catalyst: Mechanism Revision and Application to Silyl-Hilbert-Johnson Reaction

Molecules ◽

10.3390/molecules22010084 ◽

2017 ◽

Vol 22 (1) ◽

pp. 84 ◽

Cited By ~ 4

Author(s):

Chengyuan Liang ◽

Weihui Ju ◽

Shunjun Ding ◽

Han Sun ◽

Gennian Mao

Keyword(s):

Effective Synthesis ◽

Glycosyl Donors

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Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.6.80 ◽

2010 ◽

Vol 6 ◽

pp. 704-708 ◽

Cited By ~ 4

Author(s):

Andreas Sundgren ◽

Martina Lahmann ◽

Stefan Oscarson

Keyword(s):

Haemophilus Influenzae ◽

Surface Antigens ◽

Amino Group ◽

Protecting Group ◽

Primary Position ◽

Free Hydroxy Group ◽

Silyl Group ◽

Protein Conjugates ◽

Effective Synthesis ◽

Glycoconjugate Vaccines

Background: In bacteria with truncated lipopolysaccharide structures, i.e., lacking the O-antigen polysaccharide part, core structures are exposed to the immune system upon infection and thus their use as carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 6-PEtN-α-D-GalpNAc-(1→6)-β-D-Galp-(1→4)-β-D-GlcpNAc-(1→3)-β-D-Galp-(1→4)-β-D-Glcp. Results: Starting from a spacer-containing lactose derivative a suitably protected lacto-N-neotetraose tetrasaccharide structure was constructed through subsequential couplings with two thioglycoside donors, a glucosamine residue followed by a galactose derivative, using NIS/AgOTf as promoter. Removal of a silyl protecting group at the primary position of the non-reducing end residue afforded an acceptor to which the terminal α-galactosamine moiety was introduced using a 2-azido bromo sugar and halide assisted coupling conditions. Global deprotection afforded the non-phosphorylated target pentasaccharide, whereas removal of a silyl group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free spacer amino group but with a protected phosphoethanolamino group. Conjugation of the spacer amino group to biotin or dimethyl squarate followed by deprotection of the phosphoethanolamino group and, in the case of the squarate derivative, further reaction with a protein then afforded the title conjugates. Conclusion: An effective synthesis of a biologically interesting pentasaccharide structure has been accomplished. The target pentasaccharide, an α-GalNAc substituted lacto-N-neotetraose structure, comprises a phosphoethanolamine motif and a spacer aglycon. Through the spacer, biotin and protein conjugates of the title compound have been constructed to allow further use in biological experiments.

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Stereoselective Synthesis of Diglycosyl Diacylglycerols with Glycosyl Donors Bearing a β-Stereodirecting 2,3-Naphthalenedimethyl Protecting Group

The Journal of Organic Chemistry ◽

10.1021/acs.joc.0c02121 ◽

2020 ◽

Vol 85 (24) ◽

pp. 16166-16181

Author(s):

Nahoko Yagami ◽

Amol M. Vibhute ◽

Hide-Nori Tanaka ◽

Naoko Komura ◽

Akihiro Imamura ◽

...

Keyword(s):

Stereoselective Synthesis ◽

Protecting Group ◽

Glycosyl Donors

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ChemInform Abstract: Metal-Catalyzed Stereoselective and Protecting-Group-Free Synthesis of 1,2-cis-Glycosides Using 4,6-Dimethoxy-1,3,5-triazin-2-yl Glycosides as Glycosyl Donors.

ChemInform ◽

10.1002/chin.201552176 ◽

2015 ◽

Vol 46 (52) ◽

pp. no-no

Author(s):

Tomonari Tanaka ◽

Naoya Kikuta ◽

Yoshiharu Kimura ◽

Shin-ichiro Shoda

Keyword(s):

Protecting Group ◽

Metal Catalyzed ◽

Glycosyl Donors

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Metal-catalyzed Stereoselective and Protecting-group-free Synthesis of 1,2-cis-Glycosides Using 4,6-Dimethoxy-1,3,5-triazin-2-yl Glycosides as Glycosyl Donors

Chemistry Letters ◽

10.1246/cl.150201 ◽

2015 ◽

Vol 44 (6) ◽

pp. 846-848 ◽

Cited By ~ 11

Author(s):

Tomonari Tanaka ◽

Naoya Kikuta ◽

Yoshiharu Kimura ◽

Shin-ichiro Shoda

Keyword(s):

Protecting Group ◽

Metal Catalyzed ◽

Glycosyl Donors

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Synthesis of Structurally Simplified Aureolic Acid Aglycone-C-D-E Trisaccharide Analogues

Australian Journal of Chemistry ◽

10.1071/ch01198 ◽

2002 ◽

Vol 55 (2) ◽

pp. 113 ◽

Cited By ~ 3

Author(s):

W. R. Roush ◽

N. A. Powell ◽

R. A. James

Keyword(s):

Dna Binding ◽

Complex Formation ◽

Deoxyribonucleic Acid ◽

Single Step ◽

Protecting Group ◽

Acetate Ester ◽

Aureolic Acid ◽

Glycosyl Donors

Syntheses of aureolic acid analogues (5) and (6) with (2S)- and (2R)-acyloin stereochemistry, respectively, are described. The synthesis of (5) utilizes a `C + DE' glycosidation sequence, whereas analogue (6), with unnatural (2R)-acyloin stereochemistry, was synthesized by a sequence in which the entire C-D-E trisaccharide was introduced in a single step. While these syntheses provided sufficient quantities of the two aureolic acid analogues for use in studies of Mg2+ complex formation and deoxyribonucleic acid (DNA) binding, this work also highlights certain limitations in the use of 2-thiophenyl glycosyl donors for synthesis of 2-deoxy-β-glycosides. Specifically, difficulties were encountered in the identification of a protecting group for the aglycone C8 phenol that is fully compatible with the conditions required for reductive removal of the thiophenyl substituents after completion of the glycosidation sequence. Sensitivity of the C2 acyloin stereocentre to the conditions required for deprotection of a phenolic acetate ester are also highlighted in the syntheses of (5), and especially of (6).

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