DIRECT C-11 FUNCTIONALISATION OF ANATOXIN-A. APPLICATION TO THE SYNTHESIS OF NEW LIGAND-BASED STRUCTURAL PROBES

A variety of methods have been evaluated for the functionalisation of the C-11 methyl group of anatoxin-a. Reaction of N-Boc anatoxin-a 9 with PhI(OH)OTs (Koser’s reagent) represents the method of choice and gives the synthetically versatile α-tosyloxy ketone 10. This intermediate provides a convenient vehicle for the attachment of spacer units to C-11 via a thioether linkage which has been applied to the synthesis of the dansylated [N-(5-dimethylamino-1-naphthylsulfonyl)] anatoxin-a derivatives. Preliminary biological data relating to the α-thiomethyl anatoxin-a derivative 16 and the dansylated ligands, 25 and 26, are also reported.