Studies toward a total synthesis of Lactonamycin

Preece, Lewis (2012) Studies toward a total synthesis of Lactonamycin. Doctoral thesis (DPhil), University of Sussex.

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Work was undertaken towards the synthesis of the promising antibiotic lactonamycin (iii). Following the work of Parsons et al. it was proposed that cyclisation of the ene-diyne (i) would give access to advanced pentacyclic intermediate (ii) and that from this a total synthesis of lactonamycin would be achieved (scheme I).

Scheme I : Proposed Parsons, Board, Waters cyclisation to form the pentacycle (iii)(For image refer to pdf).
A synthesis towards the cyclisation precursor (i) was carried out and a route to the key tetrasubstituted phthalide (v) established. Further chemistry was proposed to complete the synthesis of lactonamycin (scheme II).

Scheme II : Formation of a fully substituted benzolactone.(For image refer to pdf).
During attempts to introduce the β-bromoallyl group of key intermediate (v) using a high temperature Claisen rearrangement it was established that the benzodioxin (vii) underwent thermolysis to generate the reactive quinone methide intermediate (viii) and that in the presence of a nucleophilic solvent the adduct (ix) was formed (scheme III). Model studies showed the reaction to be both general and high-yielding.

Scheme III : Novel quinone methide methodology. (For image refer to pdf).

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
R Medicine > RM Therapeutics. Pharmacology > RM0265 Antibiotic therapy. Antibiotics
Depositing User: Library Cataloguing
Date Deposited: 19 Jun 2012 07:14
Last Modified: 25 Aug 2015 14:55

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