Thesis-2008-Law.pdf (6.42 MB)
Novel tetramic acids via 1,3-dipolar cycloaddition
thesis
posted on 2018-08-10, 11:17 authored by Ching-Man (Carole) LawThis Ph.D. thesis has been concerned with the reinvestigation and improvement of the
intermolecular 1,3-dipolar cycloaddition strategy using isoxazoles, towards the 3-acyltetramic acids (3-acylpyrrrolidine-2,4-diones) and also the investigation and
development of the corresponding intramolecular strategy.
A second generation of the intermolecular route was developed previously within our
group and we have synthesised a variety of pyrroloisoxazoles, the 'masked' tetramic
acids. We have modified and improved both the isoxazole formations and the peptide
coupling reactions; we have further developed the chain extension at the isoxazole C-5 (tetramic acid C-3) substituent, testing the aldol-type reaction with some aromatic
aldehydes and extending it to aliphatic aldehydes. We have demonstrated the
condensation method using a strong base and hydroxyl adducts were obtained.
Dehydration has been undertaken to yield the alkenyl C-5 side-chain. Development
of the desmethyllaccarin, a derivative of the natural product laccarin, has also been
attempted via the intermolecular route.
A potential intramolecular route has the reversed sequence from the intermolecular
route, by using the N-acylation product produced from an amino acid for the
formation of a nitrile oxide and hence our building block pyrroloisoxazole by
intramolecular dipolar cycloaddition. We have generated a nitro ketoester compound
from the amino acid and investigation on the synthesis of the pyrroloisoxazole has
been undertaken.
History
School
- Science
Department
- Chemistry
Publisher
© Carole Ching Man LawPublisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2008Notes
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy at Loughborough University.Language
- en