Synthetic studies towards garsubellin A: synthesis of model systems and potential mimics by regioselective lithiation of bicyclo[3.3.1]nonane-2,4,9-trione derivatives from catechinic acid.
Bridgehead lithiations have successfully been carried out on substrates derived from catechinic acid, which possess the core bicyclo[3.3.1]nonane-1,3,5-trione structure present in garsubellin A. Using an external quench method, various electrophiles have been incorporated at the C-5 bridgehead position in a one-step process that appears to be sensitive to the substitution pattern on the bicyclic system. Regioselective lithiation at the C-3 sp(2) centre was achieved by changing the base used from LDA to LTMP. Following the introduction of a prenyl substituent by bridgehead substitution, annulation of a THF ring, analogous to that in garsubellin A, was possible via an epoxidation-ring opening sequence. Oxidative modification of the catechol substituent of the catechinic acid core was possible to give systems with muconic acid, ortho-quinone or furan 2-carboxylic acid side chains.
Ahmad
Nadia M
NM
School of Chemistry, The University of Nottingham, University Park, Nottingham, UK.
Rodeschini
Vincent
V
Simpkins
Nigel S
NS
Ward
Simon E
SE
Wilson
Claire
C
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
D019086:Bridged Bicyclo Compounds, Heterocyclic; D013729:Terpenes; C106690:garsubellin A; D002392:Catechin