M. Burns, J. Coward
Sep 1, 1996
Citations
0
Influential Citations
4
Citations
Journal
Bioorganic & medicinal chemistry
Abstract
The synthesis of two types of delta-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 delta-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 delta-amino acid as a possible inhibitor of phenethanolamine N-methyltransferase.