Synthesis of multicyclic ring systems including an alternate route to Meyers’ lactam derivatives

The first half of this product was conducted at the University of East Anglia under the supervision of Dr S.P Bew and Professor Andrew Cammidge. The potent antitumour antibiotics azinomycin A and B are of particular interest as targets for synthetic organic chemists due to their medicinal properties. The natural products comprise unique structures which includes the 1-azobicyclo[3.1.0]-hexane ring system and were originally isolated from Streptomyces sahachiroi and later from Steptomycetes griseofucus. Their structures were defined in 1983 and since then there has been significant international competition in total synthesis of azinomycin A or B. Total asymmetric synthesis of azinomycin A was achieved in 2001 however further investigation is needed to provide alternative pathways for azinomycin B. This investigation aims to synthesise compounds to then apply gold containing complexes towards the studies in formation of bicyclic aziridines; differing from current syntheses that require long reaction times and employing high temperatures. This project will aim to focus on the ability of catalytic quantities of Au(I) and or Au(III) to mediate the synthesis of 1-aza-bicyclo [3.1.1]-aziridines derived from optically active homopropargyl amines. The second half of this product was conducted at the Université et INSA de Rouen, Laboratoire COBRA (IRCOF), under the supervision of Dr Jean-François Brière and Sylvain Oudeyer within the heterocycles team directed by Dr Vincent Levacher. The groups of Wallace and Levacher developed independently in 2003 a diastereoselective construction of chiral fused oxazolidinone lactams by utilising the use of Meyers’ lactamisation methodology. This provided high atroposelection through a central C5 to axial chirality transfer. The aim of this project will be directed towards the design of alternative strategies in the synthesis of keto-ester Meyers’ lactam derivatives. Leading on to provide new atropos derivatives bearing different substituents to envisage them as novel ammonium salts for phase transfer catalysis.

Name dc:type.qualificationname

other

Level dc:type.qualificationlevel

masters

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2012

Author dc:creator

• Wightman, Daniel

Language dc:language

en