Synthesis of Structures Related to Antifreeze Glycoproteins

In this thesis, synthesis of structures related to antifreeze glycoproteins (AFGPs) are presented. Synthetic routes to a protected carbohydratederivative,2,3,4,6-tetra-O-benzyl-β-galactopyranosyl-(1→3)-2-deoxy-2-azido-4,6-di-O-benzyl-β-D-thio-1-galactopyranoside, and a tBu-Ala-Thr-Ala-Fmoc tripeptide, are described. These compounds are meant to be used in the assembly of AFGPs and analogues thereof. A Gal-GlcN disaccharide was synthesized via glycosylation between the donor, bromo-2-O-benzoyl-3,4,6-tri-O-benzyl-α-Dgalactopyranoside, and acceptor,ethyl 4,6-O-benzylidene-2-deoxy-2-N-phthalimido-β-D-1-thio-glucopyranoside, using silver triflate activation. Subsequent epimerization to a Gal-GalN disaccharide was achieved using Moffatt oxidation followed by L-selectride® reduction. The tripeptide was synthesized in a short and convenient manner using solid phase peptide synthesis with immobilized Fmoc-Ala on Wang® resins as starting point.

Contents

1. INTRODUCTION
1.1. ANTIFREEZE GLYCOPROTEINS
1.2. CARBOHYDRATES – NUMBERING AND ANOMERIC EFFECT
1.3. AIM OF PROJECT – TARGET MOLECULES AND SYNTHETIC STRATEGIES
1.3.1. Oligosaccharide Synthesis
(I) Formation of an efficient 2-O-acyl galactopyranoside
(II) Coupling of acceptor 4 with donor A
(III) Epimerization of C4 in dissaccharide B to a Gal-Gal compound C
(IV) Conversion of the N-phthalimido group
1.3.2. Peptide Synthesis
2. RESULTS AND DISCUSSION
2.1. PREPARATION OF A 2-O-ACYL GALACTOPYRANOSIDE DONOR
2.1.1. Synthesis of compound
2.1.2. Glycosylation between 2-O-acetyl donor and acceptor
2.1.3. Transformation of compound 8 to a 2-O-benzoyl donor
2.2. GLYCOSYLATION BETWEEN 2-O-BENZOYL DONOR 11 AND ACCEPTOR
2.3. SYNTHESIS OF A DERIVATIVE AVAILABLE FOR EPIMERIZATION
2.4. EPIMERIZATION TO Gal β(1→3)GalNPhth
2.5. SYNTHESIS OF A FULLY BENZYLATED Galβ(1→3)GalNPhth DERIVATIVE
2.5.1. Synthesis of Galβ(1→3)GalN3 derivative
2.6. SYNTHESIS OF THE tBu-Ala-Thr-Ala-Fmoc TRIPEPTIDE
3. SUMMARY AND FUTURE PROSPECTS
4. EXPERIMENTAL
5. APPENDIX
5.1. APPENDIX A, SYNTHETIC ROUTE TO ACHIEVE Galβ(1→3)GlcNPhth 12
5.2. APPENDIX B, SYNTHETIC ROUTE TO ACHIEVE Galβ(1→3)GalN3 2
6. ACKNOWLEDGEMENT
7. REFERENCES

Author: Fyrner, Timmy

Source: Linköping University

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