A new approach has been studied for solution-phase oligosaccharide syntheses using low molecular weight poly(ethylene glycol) monomethyl ethers (MPEG, average Mn = 550 and 750) as oligomer supports. A complex branched mannononaose (Man9) has been synthesized by this method in a very concise way to yield a large quantity of final product. Attempt has been made towards the synthesis of a heptasaccharide phytoalexin elicitor (HPE). / Model linear mannotetraose and branched mannopentaose were first tested using the novel HMB low molecular weight poly(ethylene glycol) linker. The use of this linker as the oligomer support retains the normal advantages of polymer-supported solution synthesis of oligosaccharides. Purification of the supported synthons by flash column chromatography on silica gel is greatly simplified. Another advantage of this approach is that the reaction can be monitored readily by the usual arsenal of spectroscopic techniques. Both compounds were obtained in over 10% overall yields. / In order to synthesize properly protected glycosyl donors for the construction of the mannononaose, the regioselective reductive ring opening of benzylidene acetals in carbohydrates with BH3/Bu2BOTf and regioselective acylation of hexopyranosides with pivaloyl chloride have been developed. BH 3/Bu2OTf is an effective reagent to reductively cleave 4,6- O-benzylidene acetals of various hexopyranosides to the corresponding 4-O-benzyl ethers. 4,6-O-isopropylidene acetals can be similarly cleaved. Common protecting groups are stable to the reaction conditions. On the other hand, the regioselectivity in the acylation of hexopyranosides with pivaloyl chloride in pyridine was studied. Manno- and galacto-pyranosides were regioselectively acylated to give the 3- O-pivaloylated compounds in good yields. Both methodologies have been used to provide properly protected mannoside donors and acceptors for polymannan syntheses. The regioselective reductive ring opening of 4,6- O-benzylidene acetals of hexopyranosides has also been demonstrated by concise syntheses of two building blocks of a heptasaccharide phytoalexin elicitor (HPE). / A concise synthesis of the mannan residue of a highly branched mannose type oligosaccharide present on the viral coat of HIV-1 from only two monosaccharide building blocks was achieved. The synthesis requires only five coupling steps instead of the seven or more steps required for the conventional block synthesis. In addition, even though the synthesis of HPE has not been completed to the last step, it showed that adjustment of the length of the poly(ethylene glycol) oligomer support could result in better overall yields. In both cases, 1H-1H COSY and 1H-13C HMQC NMR spectroscopies have proven to be extremely useful in monitoring the progress of oligosaccharide construction. These syntheses demonstrate that oligomer-supported solution synthesis using low molecular weight poly(ethylene glycol) is a powerful tool for the rapid and efficient preparation of complex oligosaccharides.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35712 |
| Date | January 1998 |
| Creators | Jiang, Lu, 1967- |
| Contributors | Chan, Tak-Hang (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001656606, proquestno: NQ50194, Theses scanned by UMI/ProQuest. |
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