From 2,6-Dichloronicotinic Acid to Thiopeptide Cores

The scope of 2,6-dichloronicotinic acid as a precursor of thiopeptide polyheterocylic cores has been extensively studied in a cross-coupling-based approach. Differentiation of the two chlorinated positions under SNAr conditions and versatility of the carboxylic acid are key for the preparation of 2,3,6-trisubstituted pyridines with complete regiocontrol. With the present strategy, nine different azole-substituted pyridines were synthesized. Studies towards the selective deprotection of their functionalities resulted in a set of fully orthogonal protecting groups that permits the elongation of all three pyridine substituents.