Synthesis of Carbohydrate Mimics and Development of a Carbohydrate Epimerisation Method

• Main Author: Ramstadius, Clinton
• Format: Doctoral Thesis
• Language: English
• Published: Stockholms universitet, Institutionen för organisk kemi 2010
• Subjects: Carbohydrate Mimic; Ring-closing Metathesis; Carbohydrate Chemistry; Carbasugar; Aminocarbasugar; Pseudodisaccharide; Glycosidase and Lectin Inhibitors; Organic chemistry; Organisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-45855; http://nbn-resolving.de/urn:isbn:978-91-7447-170-0

In this thesis the synthesis of several hydrolytically stable carbohydrate mimics with the potential to function as glycosidase or lectin inhibitors are described. This work is presented in Chapters 2-5. Chapters 2 and 3 describe synthetic efforts for producing carbasugars, and include the first synthesis of 1,2-bis-epi-valienamine and the preparation of two previously known aminocarbasugars. All three compounds were synthesised starting from D-mannose, using ring-closing metathesis as the key step. 1,2-Bis-epi-valienamine was found to inhibit Cellulomonas fimi β-mannosidase with a Ki value of 140 mM. Also included is the development of a novel synthetic route from cheap D-fructose to three mannose-mimicking carbasugars using a ring-closing metathesis strategy. Two of the compounds are potential inhibitors of the FimH adhesin. In Chapters 4 and 5 the synthesis of a number of pseudodisaccharides are presented; valienamine- and epi-valienamine-containing pseudodisaccharides and a small library of S-linked pseudodisaccharides were prepared. Various synthetic strategies were explored, including an alkylation strategy, Mitsunobu couplings, and sulfonate displacements. This is the first report on the synthesis of a valienamine pseudodisaccharide with β-lyxo-configuration. Two of the S-linked pseudodisaccharides were found to bind to Concanavalin A with high affinity. The final chapter (Chapter 6) of this thesis focuses on the development of a carbohydrate epimerisation method using transition metal catalysis. Two equilibrium constants involving gluco/manno- and gluco/allo-alcohols were determined via this method. === At the time od doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Manuscript. Paper 5: Manuscript.