Part I. Synthesis, properties, and applications of oligosubstituted bullvalenes. Part II. Preparation of C-terminal alpha-ketoacids and N-terminal hydroxylamines for decarboxylative peptide ligations.

Format:

Book

Thesis/Dissertation

Author/Creator:

Lippert, Alexander Ryan.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Chemistry, Organic.

0490.

Local Subjects:

0490.

Physical Description:

299 pages

Contained In:

Dissertation Abstracts International 70-01B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Part I. Bullvalene is a ten-carbon molecule whose unique bonding pattern endows it with the intriguing ability to spontaneously alter its molecular arrangement through degenerate strain-assisted Cope rearrangements. Hypothesizing that this fluxional molecule could be elaborated to form an adaptive organic molecule capable of responding to external stimuli, an efficient ten-step synthetic route, featuring a key intramolecular cyclopropanation of a novel sulfur ylide, to yield a tetrasubstituted bullvalene has been developed. Elaborate functionality, such as porphyrins, was incorporated onto this shape shifting scaffold using cross metathesis. Cope rearrangements of the bullvalene core allow these molecules to exist in a dynamic equilibrium of more than 800 constitutional isomers. Explorations into the interaction of the shape shifting bisporphyrin bullvalene with C60 have revealed an active network of interconverting species that appear to adapt to more tightly bind to the molecular guest.

Part II. In order for the novel decarboxylative amide forming reaction between alpha-ketoacids and hydroxylamines to find use as a practical method for peptide ligation, it is crucial to have facile methods to install these functionalities onto the C-terminus and N-terminus of peptides. The preparation of C-terminal peptidic alpha-ketoacids has been accomplished through the mild oxidation of bench stable peptidic cyanosulfur ylides. The cyanosulfur ylides can be readily prepared using standard peptide coupling conditions and the oxidation conditions are compatible with most amino acid side chains. In addition, a highly chemoselective method for the production of N-terminal glycine hydroxylamines has been established through a short sequence of orthogonal reactions, including a chemospecific oxidation of an N-terminal glycine, oxime formation, and selective reduction. This method can be utilized on completely unprotected peptides.

Notes:

Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0298.

Adviser: Jeffrey Bode.

Thesis (Ph.D.)--University of Pennsylvania, 2008.

Local Notes:

School code: 0175.

ISBN:

9781109008296

Access Restriction:

Restricted for use by site license.