2,5 Dihydrooxazole-3-oxides: Design of a protecting group for alpha-ketoacids and application for the synthesis of peptide-derived alpha-ketoacids.

Format:

Book

Thesis/Dissertation

Author/Creator:

Flores, Melissa Amy.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Chemistry, Organic.

Biochemistry.

0487.

0490.

Local Subjects:

0487.

0490.

Physical Description:

308 pages

Contained In:

Dissertation Abstracts International 71-11B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Our group has demonstrated the chemoselective decarboxylative condensation of unprotected peptide fragments via an N-terminal hydroxylamine and a C-terminal alpha-ketoacid. Access to the requisite enantiopure peptide-derived alpha-ketoacids has presented a challenge, and the development of synthetic methods for the preparation of alpha-ketoacids are crucial to the success of this project. We disclose a strategy for the chemoselective protection of alpha-ketoacids via direct annulation with oximes to afford 2,5-dihydrooxazole-3-oxides. The resulting cyclic nitrones are configurationally stable, and can be easily elaborated and modified; deprotection is achieved under mild aqueous conditions. We have extended this approach to the synthesis of peptide alpha-ketoacids in solution and solid phase. Successful application of this protocol will facilitate the synthesis of enantiopure peptide-derived alpha-ketoacids without the need for our previously reported late-stage oxidation.

Notes:

Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: 6755.

Advisers: Jeffrey W. Bode; Gary Molander.

Thesis (Ph.D.)--University of Pennsylvania, 2010.

Local Notes:

School code: 0175.

ISBN:

9781124276632

Access Restriction:

Restricted for use by site license.