Synthetic Studies Towards the Core Structure of Nakadomarin A by a Thioamide-Based Strategy.
The tricyclic BCD substructure of the marine natural product nakadomarin A has been synthesised. The strategy utilised a key carbon-carbon bond-forming reaction between a furan and anN-acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.
Department of Chemistry, University College London Christopher Ingold Building, 20 Gordon Street, London, WC1H 0AJ, UK.
Jai K
JK
Chavda
GlaxoSmithKline Research & Development Limited, Medicines Research Centre Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Panayiotis A
PA
Procopiou
UK National Crystallography Service, School of Chemistry, University of Southampton Southampton, SO17 1BJ, UK.
Peter N
PN
Horton
UK National Crystallography Service, School of Chemistry, University of Southampton Southampton, SO17 1BJ, UK.
Simon J
SJ
Coles
Department of Chemistry, University College London Christopher Ingold Building, 20 Gordon Street, London, WC1H 0AJ, UK.
Michael J
MJ
Porter
Alkaloids; Multicomponent reactions; Natural products; Sigmatropic rearrangement