Title

Studies directed towards syntheses of multivalent carbohydrates suitable for binding to E. coli Shiga-like toxin

Date of Award

2003

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor(s)

Watson J. Lees

Keywords

Shiga toxins, Trisaccharides, Cyclodextrin, Carbohydrates

Subject Categories

Chemistry | Organic Chemistry | Physical Sciences and Mathematics

Abstract

In order to investigate multivalent binding enhancement between carbohydrate molecules and Shiga-like toxins, two different synthetic approaches were performed: (1) synthesis of polymerizable C-1 modified P k trisaccharide and (2) synthesis of trisaccharide-branched α-cyclodextrin.

A polymerizable C-1 modified P k trisaccharide derivative 88 was synthesized through ten steps from lactose with 3.5% overall yield. The synthetic route included three coupling reactions: α-glycosidic coupling of lactose unit 18 and galactose unit 20 , β-glycosidic coupling of trisaccharide trichloroacetimidate 28 and methyl ester linker 72 , and amide bond formation between the carboxylic end of trisaccharide 90 and the amine linker 89 . As a continuation of the research, the compound 88 will be copolymerized with acrylamide in varying ratios to form linear polymers to be subjected for assay.

Trisaccharide-branched α-cyclodextrin 111 was synthesized by coupling trisaccharide 90 to α-cyclodextrin via a spacer arm. Incorporation of a spacer arm to α-cyclodextrin included perbromination of the primary hydroxyl groups on α-cyclodextrin followed by a substitution reaction with a thiol linker 107 with 14.6% yield. The coupling of trisaccharide 90 to spacer-arm linked α-cyclodextrin yielded the desired hexakis-substituted product 110 along with less substituted products. The collected yield of the desired product was 33%, however, we were not able to fully characterize this compound 110 or the hydrolyzed product 111 due to the limited amount available. Our synthesis of persubstituted trisaccharide-branched α-cyclodextrin was one of the first attempts to synthesize persubstituted α-cyclodextrin with relatively large molecules. These compounds will be submitted for binding assays.

Access

Surface provides description only. Full text is available to ProQuest subscribers. Ask your Librarian for assistance.

http://libezproxy.syr.edu/login?url=http://proquest.umi.com/pqdweb?did=764806071&sid=1&Fmt=2&clientId=3739&RQT=309&VName=PQD

Share

COinS