Synthesis of Purine - Amino Acid Conjugates

Abstract

4. Conclusions A simple and efficient approach to the synthesis of (purin-6-yl)alanines based on Negishi cross-coupling reactions of 6-iodopurines and iodozinc- alanines applicable to the synthesis of both racemic and optically pure compounds was developed. Though analogous reactions were used before for the synthesis of some simple aryl- or hetarylaranines, this was the first successful use in the functionalization ofprotected nucleobases and nucleosides. A practical method for synthesis of enantiomerically pure (purin-6_ yl)phenylalanines by palladium catalyzeď, copper mediated Stille cross-coupling reactions ofprotected 4-(trimethylstanyl)phenylalanines and 6-iodopurines was developed. This method was used in the synthesis of series of (purin_6_ yl)phenylalanines (bases and nucleosides) varying in substitution in position 9 of purine scaffold and in absolute configuration on o-carbon ofphenylalanine. The shaughnessy method for the Suzuki cross-coupling reactions in aqueous media was further optimized and applied to the single-step synthesis of novel optically pure (adenin-8-yl)phenylalanines and (purine_6_yl)phenyl_ alanines. wide tolerance of this methodology towards variety of functionalities and its applicability to 1abile systems was demonstrated particularly by the very first examples of couplings...

4. Conclusions A simple and efficient approach to the synthesis of (purin-6-yl)alanines based on Negishi cross-coupling reactions of 6-iodopurines and iodozinc- alanines applicable to the synthesis of both racemic and optically pure compounds was developed. Though analogous reactions were used before for the synthesis of some simple aryl- or hetarylaranines, this was the first successful use in the functionalization ofprotected nucleobases and nucleosides. A practical method for synthesis of enantiomerically pure (purin-6_ yl)phenylalanines by palladium catalyzeď, copper mediated Stille cross-coupling reactions ofprotected 4-(trimethylstanyl)phenylalanines and 6-iodopurines was developed. This method was used in the synthesis of series of (purin_6_ yl)phenylalanines (bases and nucleosides) varying in substitution in position 9 of purine scaffold and in absolute configuration on o-carbon ofphenylalanine. The shaughnessy method for the Suzuki cross-coupling reactions in aqueous media was further optimized and applied to the single-step synthesis of novel optically pure (adenin-8-yl)phenylalanines and (purine_6_yl)phenyl_ alanines. wide tolerance of this methodology towards variety of functionalities and its applicability to 1abile systems was demonstrated particularly by the very first examples of couplings...