Synthesis of astin C and astin G and hydroxylated analogs / Kelly Kathleen Schumacher.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Schumacher, Kelly Kathleen.

Contributor:

Joullié, Madeleine M., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

xxix, 327 pages : illustrations ; 29 cm

Production:

1998.

Summary:

The astins are a family of cyclopentapeptides isolated from the biologically active extracts of the root of Aster tataricus (Compositae), a flowering plant native to Siberia. The root of this plant has been used for centuries in Chinese medicinal teas to relieve nausea and fevers. All astins have a cyclopeptide backbone composed of L-beta-phenylalanine, L-alpha-aminobutyric acid (or L-allo-threonine), L-serine, and one of a variety of substituted prolines. Serine is the only coded amino acid found in these structures. The most interesting of these amino acids is the cis-3,4-dichloroproline found in the only astins with antitumor properties, astins A, B, and C. Only one other isolated compound, cyclochlorotine, contains this unusual amino acid. Another novel feature of the astins is the cis amide bond between dichloroproline, and aminobutyric acid5. This feature is the major structural difference between astins A, B and C, and cyclochlorotine, and is believed to be responsible for a noticeable difference in biological activity of the compounds.

The synthesis of the noncoded amino acids present in the astins will be described herein. Prior to the initiation of this research project, there was no reported synthesis of 3,4-dichloroproline. Although syntheses of the remaining noncoded amino acids had been published previously, more efficient methods were necessary for large scale synthesis of the astins. The synthesis of astin G, containing natural proline, will be described. In addition, the syntheses of two hydroxylated proline analogs will be described as a route toward astin C. Main features of this work include improvement of the synthesis of 3,4-dihydroxyproline, stereospecific synthesis of cis-3,4-dichloroproline, a study of routes toward the alpha-chloroenamine of astins D, E and H, and metal-catalyzed peptide cyclization techniques.

Notes:

Supervisor: Madeleine M. Joullie.

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 1998.

Includes bibliographical references and index.

Local Notes:

University Microfilms order no.: 99-13518.

OCLC:

187478186