Ring-Opening of Aziridine -2 -Carboxamides by Carbohydrate C1-O Nucleophiles. Stereoselective Preparation of O-Linked Glycopeptides

A new method for the synthesis of O-linked glycopeptides is described. The method uses the carbohydrate C1-O nucleophilic ring-opening of aziridine-2-carboxamides to access the target O-linked glycopeptides. The synthesis of the alpha-GalNAc-Ser class of glycopeptides is emphasized and either the alpha- or beta-glycoside can be accessed by judicious selection of solvent and metal counter-ion, even in the presence of the native carbohydrate C2-NHAc group. Other classes of 0-glycosyl serine constructs, such as the beta-GlcNAc-Ser and alpha-Man-Ser linkages, are also prepared by this approach. In the course of these studies, the ortho-allylbenzyl (ABn) moiety was developed as a new C-terminus secondary amide protective group for carboxylic acids, which allows for oxidative C-terminus extension of amino acids following the carbohydrate-aziridine coupling reaction. A new protocol for deprotection of p-nitrobenzenesulfonamides with in situ peptide coupling is also reported. This reaction allows for direct N-terminus extension of p-nitrobenzenesulfonyl protected amino acids, or glycosyl amino acids, in one synthetic step.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Ryan, Daniel

Contributors dc:contributor

• Gin, David Y.

• Chemistry, Organic

Language dc:language

eng

Identifier

(MiAaPQ)AAI3363079

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84338