Total synthesis of enamide-containing natural products

Pasqua, Adele Elisa (2013) Total synthesis of enamide-containing natural products. PhD thesis, University of Glasgow.

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Abstract

Enamides are an important class of functional group commonly present in natural products and drug candidates. In particular, enamides and dienamides are common in many anti-parasitic and anti-cancer natural products and pharmaceutical drug leads. The enamide moiety is strictly related to the biological activity of such compounds as it is directly involved in their mode of action. Due to the great importance of the enamide moiety in biological and medicinal chemistry, a deep interest has risen in the synthetic community in the past two decades and a wide variety of methodologies for the preparation of enamides have been developed so far. However, current methods suffer from poor efficiency and stereocontrol, in particular in the case of the thermodynamically unfavoured (Z)-enamides. The work reported herein details the development of a new methodology for the stereoselective synthesis of β-halo-enamides and β,β-dihalo-enamides from which it is possible to synthesise, via Pd-mediated cross-coupling reactions, more complex structures, such as β-yn-enamides, stereodefined (E,Z)-dienamides and branched products. In addition, oxazoles can be achieved via basic treatment of β-halo-enamides. The methodology has been successfully applied to the total syntheses of simple enamide-containing natural products, such as lansiumamide A, lansiumamide B and alatamide. The total synthesis of a more complex family of enamide-containing natural products, such as the antifungal, antibiotic and cytotoxic crocacins, was also explored. The attention was focused firstly on (+)-crocacin C that is the primary amide and can be envisioned as the synthetic precursor of the other crocacins, and secondly on (+)-crocacin D, that is the most active and promising of the family. Two novel syntheses of (+)-crocacin C and (+)-crocacin D are therefore reported. The synthesis of simplified unnatural analogues with some promising insecticidal activity is also described.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Enamides, Wittig olefination, beta-halo-olefins, Natural products, Total synthesis, Crocacins
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Funder's Name: UNSPECIFIED
Supervisor's Name: Marquez, Dr. Rodolfo
Date of Award: 2013
Depositing User: Miss Adele Elisa Pasqua
Unique ID: glathesis:2013-4088
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Mar 2013 11:44
Last Modified: 11 Mar 2013 11:45
URI: http://theses.gla.ac.uk/id/eprint/4088

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