Abstract

An assessment of the relative O-3/O-4 reactivities of both methyl α- and β-d-glycosides of N-dimethylmaleoyl (DMM) d-glucosamine acceptors protected at O-6 with benzoyl (Bz), benzyl (Bn), and tert-butyldiphenylsilyl (TBDPS) groups is presented using per-O-benzoylated β-d-galactofuranosyl and per-O-acetylated α-d-galactopyranosyl trichloroacetimidates as glycosyl donors. Using the former donor, the α anomer of the 6-O-benzoylated compound gave exclusive substitution at O-3, whereas the other two compounds with α-configuration kept this site as preferential. The β anomer of the 6-O-benzoylated compound gave the same amounts of reaction products on O-3 and O-4, whereas the other β analogs carried a more reactive O-4. The same reactions were carried out using as donor the less-reactive per-O-acetylated α-d-galactopyranosyl trichloroacetimidate. Although the same trend was found to occur, the O-4 was always relatively more reactive with the pyranosyl donor than with the furanosyl donor, when keeping the remaining factors constant. Furthermore, the β anomers of the acceptor gave almost exclusive substitution at O-4. These observations confirm and extend the utility of these ‘matching’ donor and acceptor reactivities.

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Keywords: Glucosamine acceptors; N-Dimethylmaleoyl group; Galactofuranosyl donor; Galactopyranosyl donor; Regioselectivity

Article Outline

1. Introduction

2. Results and discussion

3. Experimental

3.1. Competition experiments

3.1.1. Competitive experiment of reactivity of donors 9a and 2b with methanol

3.1.1.1. Data for 9b

3.1.1.2. Data for 2c

3.1.2. Competitive glycosylation experiment of donors 9a and 2b with acceptor 10a

3.1.2.1. Disaccharide 10b

3.1.2.2. Disaccharide 10c

3.2. General procedure for glycosylation and acetylation reactions

3.2.1. Methyl 6-O-benzoyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (11a)

3.2.2. Methyl 6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (11b)

3.2.3. Methyl 6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (11c)

3.2.4. Methyl 6-O-benzoyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (12a)

3.2.5. Methyl 6-O-benzyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (12b)

3.2.6. Methyl 6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (12c)

3.2.7. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (15b)

3.2.7.1. Disaccharide 15a

3.2.7.2. Acetate 15b

3.2.8. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (15d) and methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (16b)

3.2.8.1. Disaccharide 15c

3.2.8.2. Acetate 15d

3.2.8.3. Disaccharide 16a

3.2.8.4. Acetate 16b

3.2.9. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (15f) and methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→4)-3-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (16d)

3.2.9.1. Disaccharide 15e

3.2.9.2. Acetate 15f

3.2.9.3. Disaccharide 16c

3.2.9.4. Acetate 16d

3.2.10. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (17b) and methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→4)-3-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (18b)

3.2.10.1. Disaccharide 17a

3.2.10.2. Acetate 17b

3.2.10.3. Disaccharide 18a

3.2.10.4. Acetate 18b

3.2.11. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (17d) and methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (18d)

3.2.11.1. Disaccharide 17c

3.2.11.2. Acetate 17d

3.2.11.3. Disaccharide 18c

3.2.11.4. Acetate 18d

3.2.12. Methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→3)-4-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (17f) and methyl 2,3,5,6-tetra-O-benzoyl-β-d-galactofuranosyl-(1→4)-3-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (18f)

3.2.12.1. Disaccharide 17e

3.2.12.2. Acetate 17f

3.2.12.3. Disaccharide 18e

3.2.12.4. Acetate 18f

3.2.13. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→3)-4-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (19b) and methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (20b)

3.2.13.1. Disaccharide 19a

3.2.13.2. Acetate 19b

3.2.13.3. Disaccharide 20a

3.2.13.4. Acetate 20b

3.2.14. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→3)-4-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (19d) and methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (20d)

3.2.14.1. Acetate 19d

3.2.14.2. Acetate 20d

3.2.15. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→3)-4-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (19f), methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (20f) and methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→3)-[2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)]-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-α-d-glucopyranoside (21)

3.2.15.1. Acetate 19f

3.2.15.2. Acetate 20f

3.2.15.3. Trisaccharide 21

3.2.16. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→3)-4-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (22b) and methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-benzoyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (23b)

3.2.16.1. Acetate 22b

3.2.16.2. Disaccharide 23a

3.2.16.3. Acetate 23b

3.2.17. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (23d)

3.2.17.1. Disaccharide 23c

3.2.17.2. Acetate 23d

3.2.18. Methyl 2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl-(1→4)-3-O-acetyl-6-O-tert-butyldiphenylsilyl-2-deoxy-2-dimethylmaleimido-β-d-glucopyranoside (23f)

3.2.18.1. Disaccharide 23e

3.2.18.2. Acetate 23f

Acknowledgements

Supplementary data

References