Minimally Competent Lewis Acid Catalysts. General Methods for the Synthesis and Separation of Diastereomeric Mixtures of Monorhamnolipids of Pseudomonas aeruginosa with Peracetate Glycoside Donors

Abstract

Rhamnolipids are rhamnose-based glycolipids with strong biosurfactant properties. Because they are naturally occurring surfactants found in Gram-negative bacterial walls, rhamnolipids are biodegradable, low in toxicity and have the potential for bioremediation. However, rhamnolipids are biosynthesized as a large mixture of congeners, making purification poor and scalability difficult. The "green" properties of the compound make it a highly desirable alternative for the many carcinogenic and toxic synthetic surfactants on the market. A method for synthesizing rhamnolipids cost-effectively and at a large scale is highly desirable in a competitive surfactant industry. There is a large amount of literature for glycolipid synthesis, as well as literature for small-scale libraries of rhamnolipid congeners. However, many syntheses involve expensive reagents, dangerous procedures and low-yielding reactions. Therefore, many modifications are made in this dissertation in order to eliminate these problems and limitations. Modifications include standard reduction reactions, easily removable protecting groups and glycosylations utilizing minimally competent Lewis acid promoters. Other techniques involve enantiomer-to-diastereomer conversion for attaining all stereoisomers of the rhamnolipid congeners for comparison and analysis in an efficient manner. A general, cost-effective synthesis for monorhamnolipids is achieved and discussed in the following dissertation. The generality allows for synthesis of glycolipids with different carbohydrates and a variety of primary and secondary lipid alcohols, with varying hydrocarbon chain lengths. Additionally, the synthesis utilizes enantiomer-to-diastereomer conversion via glycosylation for the synthesis and purification of all rhamnolipid diastereomers in a single synthesis. This makes it possible to analyze surface properties and structure-activity relationships of the different congeners and their respective stereochemistry. The synthesis minimizes reaction steps, cost and time required of previously published rhamnolipid syntheses and is general for utilization in the future synthesis of rhamnose- and non-rhamnose-based derivatives, dirhamnolipids, and rhamnolipid polymers.