CH activation and CH2 double activation of indolines: towards the synthesis of aspidospermidine and aspidofractinine

This thesis is concerned with the total synthesis of the two Aspidosperma alkaloid natural products, aspidospermidine and aspidofractinine. The two targets have a common pentacyclic molecular framework unique to this class of indole alkaloids.<br/><br/>Aspidospermidine has previously proven an attractive target, with over 20 total syntheses completed. The hexacyclic framework of aspidofractinine has proven more challenging, with only 5 total syntheses to date. These synthetic approaches are discussed in Chapter 1 together with the pharmacological activity exhibited within the Aspidosperma alkaloid series.<br/><br/>Chapter 3 details the challenges of installing the first 4 rings of the targets (the ABDE ring system). Ring expansion of a C3 cyclopropyl indolone with an imine, ultimately provided a quick and efficient route to the tetracyclic structure. With the model system realised, Chapter 3 details the synthetic efforts towards an elaborated imine component and its subsequent use in the ring expansion methodology to give our key precursor.<br/><br/>Chapter 4 discusses model systems to prove our key radical translocation step can be achieved. Systems are described that show intramolecular translocation of an aryl radical to C2 of an indoline is a feasible means of elaborating this centre.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2009

Author dc:creator

• Whiting, Sally

Advisor dc:contributor.advisor

• Harrowven, David