The stereospecific formation of 1,2-cis glycosides via allyl-mediated intramolecular aglycon delivery

Thesis

This thesis describes investigations into the possibility and scope of allylderived intramolecular aglycon delivery as a tool for the stereospecific formation of 1,2-cis glycosides. The three-step procedure involves isomerisation of the 2-O-allyl protection of a glycosyl donor, followed by iodonium-mediated tethering to an aglycon alcohol. Activation of the donor induces intramolecular delivery of the aglycon, to afford the 1,2-cis glycoside.

The synthesis of ten glycosyl donors, including gluco-, manno- and rhamnopyranosyl and glucofuranosyl donors, as selenoglycosides, thioglycosides and glycosyl fluorides, is described.

Isomerisation was carried out in excellent yield in all cases using a catalyst derived from Wilkinson's catalyst.

The scope of N-Iodosuccinimide-mediated tethering is described. Attempted tethering to a selenoglycoside resulted in activation of the donor. Tethering to a thiomethyl glycoside was successful for unhindered alcohols, but sluggish for secondary carbohydrates, and activation of the donor became competitive in these cases. The use of glycosyl fluorides gave good tethering yields for many alcohols, including secondary carbohydrates. For hindered alcohols, tethering of succinimide became competitive, resulting in reduced yields.

Examples of high-yielding tethering reactions using a novel source of iodonium ion are reported. A large excess of aglycon was unnecessary for good yields to be obtained. A 'reverse' tethering approach, whereby a donor with a free 2-hydroxyl is tethered to the isomerised allyl group of an aglycon, was found to be effective using this reagent.

In all cases, activation gave stereospecific glycosylation, furnishing the 1,2-cis glycosides. Other glycosylated products still bearing functionality derived from the tether, including mixed acetals and enol ethers, were cleaved by acid treatment, affording further 1,2-cis glycoside. Slightly lower glycosylation yields were obtained in the rhamno and glucofurano systems. Investigations into the glycosylation mechanism were also undertaken.

The stereospecific synthesis of the Glc 3 Man N-glycan tetrasaccharide via an iterative tethering and allyl-mediated intramolecular glycosylation strategy is reported.

Authors: Cumpstey, I; Cumpstey, Ian

• Publication date: 2002
• DOI: 10.5287/ora-2ajog9qdy
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Glycosides; Oligosaccharides; Synthesis