Open Access Dissertation
Date of Award
SYNTHESIS OF BRADYRHIZOSE AND THE EQUATORIAL GLYCOSIDES OF 3- DEOXY-D-MANNO-OCT-2-ULOSONIC ACID
Chapter one provides a general view on the background to the research in two parts. The first part begins with an introduction on the significance of the lectin-carbohydrate interactions in leguminous plants. Then the structure and role of O-antigen lipopolysaccharides in the symbiotic nitrogen cycle, and the mechanism and significance of the cycle in leguminous plants growth are introduced. The role, isolation and characterization of bradyrhizose are also introduced; and the previous syntheses of bradyhizose and of related bicyclic compounds presented.
The second part of chapter one starts with an introduction on the biosynthesis, role and occurrence of KDO in bacterial LPS and CPS. The second part also introduces the implications of KDO in
glycoconjugate vaccine development, and highlights literature syntheses of equatorial KDO glycosides. The role of side chain conformation in stereocontrolled glycosylation reactions, in particular the influence of side chain conformation in stereoselective synthesis of neuraminic and pseudaminic glycosides, are then broadly discussed.
Chapter two describes the synthesis of bradyrhizose in 14 steps and 6% overall yield from commercially available and cheap D-glucose. Unlike the literature synthetic approaches to this unsual bicyclic sugar, the synthesis involves the elaboration of a trans-fused carbocyclic ring onto the pre-exisiting glucopyranose framework followed by adjustment of the oxidation levels by simple practical methods. The key steps in this synthesis are radical extension of the glucopyranose side chain under photocatalytic conditions using fac-Ir(ppy)3 as the catalyst, construction of the bicyclic motif using ring closing metathesis, regioselective allylic oxidation, Luche reduction, hydroxy-directed epoxidation, regio- and stereoselective acid-catalyzed epoxide opening, and deprotection.
Chapter three begins with an introduction to the pseudosymmetric relationship of the bacterial pseudaminic acid and 3-deoxy-D-manno-oct-2-ulosonic acid. Then, a brief discussion on the excellent equatorial selectivity obtained with the pseudaminic acid donor having the equatorially selective tg conformation about its C6-C7 bond is presented. This is followed by a prediction that suitably protected KDO donors will adopt the trans,gauche conformation of their side chain and consequently be highly equatorially selective in their coupling reactions conducted under standard conditions. The synthesis and conformational analysis of peracetylated, perbenzylated KDO donors, acetonide protected donor, and the silylene‐protected KDO donor is then described. Consistent with the predictions, good to excellent equatorial selectivity is observed on coupling
of acetonide-protected, per-O-acetyl or benzyl-protected KDO donors at low temperatures, while axial selectivity is seen on coupling of the axially selective silylene‐protected KDO donor at low temperature.
Chapter four presents progress on the proposed convergent synthesis of the pentasaccharide containing the tetrasaccharide repeating unit of K. kingae type c capsular polysaccharide. The chapter begins with the background on K. kingae and its mode of infection. The synthesis of key donors and acceptors as building blocks is then described. Finally, a plan for completion of the synthesis is described.
Chapter 6 provides the full experimental details and characterization data for all compounds prepared.
Ngoje, Philemon O., "Synthesis Of Bradyrhizose And The Equatorial Glycosides Of 3-Deoxygenation-D-Mango-Oct-2-Ulosonic Acid" (2020). Wayne State University Dissertations. 2498.