Synthesis of complex δ-acetylenic amino acids as potential multisubstrate adduct inhibitors of methyltransferases

Article abstract of DOI:10.1016/0968-0896(96)00139-3

The synthesis of two types of δ-acetylenic amino acids is described. Key intermediates were derived from terminal acetylenes via two different routes: (1) palladium-mediated, Heck-type arylation, and (2) Simmons-Smith homologation followed by reaction of the resulting propargylic organometallic with a benzoyltrimethylsilane. Further elaboration to the desired amino acids involved the coupling of carbanions derived from N-benzylidene glycine esters to complex alkyl halides. The synthesis of nonnucleoside δ-acetylenic amino acids was successfully effected using this chemistry. In the case of the nucleoside-containing amino acids, a potential multisubstrate adduct: inhibitor of catechol O-methyltransferase was synthesized via this route. Unfortunately, the sensitivity to acid of 5'-deoxy, 5'-carbanucleosides prevented successful completion of the synthesis of a second nucleoside-containing δ-amino acid as a possible inhibitor of phenethanolamine N-methyltransferase.