Synthesis of Ellagic Acid Glycoside Derivatives found in Rubus ulmifolius Open Access

Jariwala, Parth Balvant (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/bc386j791?locale=en
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Abstract

The dramatic increase in the number of antibiotic-resistant bacteria is a major problem in the field of public health. A novel approach to killing antibiotic-resistant bacteria employs compounds to shutdown bacterial defense mechanisms, thereby increasing the efficacy of current antibiotics at killing the bacteria. A previous study by Quave et al. found that an extract from Rubus ulmifolius inhibits biofilm formation, a defense mechanism, in S. aureus. The extract contains high levels of glycosidic derivatives of ellagic acid. The primary goal of this project is to synthesize and test glycosidic derivatives of ellagic acid for anti-biofilm and growth inhibitory activity in order to study structure activity relationships. The main synthetic approach taken is directly glycosylating ellagic acid. Several methods have been tried to glycosylate ellagic acid, and some have led to product formation, but more optimization is required to produce the glycosidic derivatives in higher yields.

Table of Contents

Introduction 1

Approaches to Synthesizing Ellagic Acid Glycosides 4

Chemical and Physical Properties of Ellagic Acid 7

Results and Discussion 8

Future Directions 20

Experimental 21

References 25

Figures, Tables, and Schemes:

Figure 1: Ellagic acid 7

Figure 2: Formation of quaternary ammonium salt intermediate 12

Figure 3: Analogs of ellagic acid 20

Table 1: Sugars utilized for glycosylation 15

Scheme 1: Preparation of 4,4'-di-O-methylellagic acid 5

Scheme 2: Hydrolysis of ellagic acid in basic conditions 7

Scheme 3: Preparation of 1,2,3,4-tetra-O-acetyl-α-L-rhamnopyranose 8

Scheme 4: Proposed mechanism for neighboring group assistance

in per-O-acetyl rhamnopyranose 9

Scheme 5: Glycosylation of ellagic acid using BF3 as a catalyst 10

Scheme 6: Preparation of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl ellagic acid 11

Scheme 7: Glycosylation mechanism when using TBAI 17

Scheme 8: Deprotection of tetrakis-TIPS ellagic acid using TASF 18

Scheme 9: Preparation of tris-TIPS, (2,3,4-tri-O-TMS-α-L-rhamnopyranosyl)

ellagic acid 19

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