Synthesis of vertilecanin C and two new derivatives of vertilecanin A via nicotinic acid

Vertilecanin C and 2 new phenyl-substituted derivatives of vertilecanin A were synthesized. Lithiation of 5-benzoylpicolinamide with BuLi at -78 degrees C followed by treatment with methyl bromoacetate gave vertilecanin C [methyl 2-(3-benzoylpicolinamido) acetate], a natural product. Vertilecanin A type phenopicolinic acid derivatives were synthesized starting from nicotinic acid in 4 steps. Chlorination of nicotinic acid with SOCl(2) followed by treatment with anisole in the presence of AlCl(3) gave (4-methoxyphenyl)(pyridin-3-yl) methanone. The Minisci reaction of the ketone afforded 5-(4-methoxybenzoyl) picolinamide. TiCl(4)-catalyzed acidic hydrolysis of the picolinamide gave 5-(4-methoxybenzoyl) picolinic acid, from which 5-( hydroxy(4-methoxyphenyl) methyl) picolinic acid was obtained by selective reduction with NaBH(4). The same reaction sequence performed with toluene instead of anisole afforded 5-(hydroxy(p-tolyl) methyl) picolinic acid.