Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring.
New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.
Shannon
Simon K
SK
Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, MN 55455, USA.
Peacock
Mandy J
MJ
Kates
Steven A
SA
Barany
George
G
D008012:Lidocaine / Q000138:chemical synthesis* / Q000737:chemistry; D011342:Procainamide / Q000138:chemical synthesis* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
D008012:Lidocaine; D011342:Procainamide