ABSTRACT
Blending synthetic biology and synthetic chemistry represents a powerful approach to diversity complex molecules. To further enable this, compatible synthetic tools are needed. We report the first Buchwald Hartwig amination reactions with unprotected halotryptophans under aqueous conditions and demonstrate this methodology is applicable also to the modification of unprotected tripeptides and the natural product barettin.
Subject(s)
Oligopeptides/chemistry , Peptides, Cyclic/chemistry , Tryptophan/analogs & derivatives , Water/chemistry , Amination , Aniline Compounds/chemistry , Catalysis , Halogens/chemistry , Oligopeptides/chemical synthesis , Palladium/chemistry , Tryptophan/chemical synthesisABSTRACT
The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.
