Studies towards the synthesis of the antibiotic lactonamycin

Transition metal-free, thermal cyclisation methodology has been demonstrated previously in the Parsons group, with the vision of applying the process to a novel synthesis of the antibiotic Lactonamycin. i. The synthesis of the aglycone of i has been proposed from the pentacyclic intermediate ii, which itself is the hypothesised product of the Parsons-BoardWaters cyclisation of the ene-diyne iii. (Scheme A - see thesis abstract) The phthalide v was synthesised from 2,5-dimethoxybenzaldehyde in 3 steps in moderate yield and was seen as a common starting material for the subsequent routes devised to provide the key aldehyde vi. A further mode of complexity was proposed by attempting to perform the Claisen rearrangement of the alkene vii in cascade with the aforementioned cyclisation to give the amide ii. (Scheme B - see thesis abstract)Open Acces