2002 alkaloids

alkaloidsU 0600

01 - 216Synthesis and Acetylcholinesterase Inhibition of 5-Desamino Hu-perzine A Derivatives. — In order to examine the role of the aminofunctionality of huperzine A on the biological activity, the 5-desamino huperzineA derivatives (XIX) and (XX) are prepared using a new strategy towards thehuperzine A skeleton. Wittig olefination of ketone (XIII) yields a 2:3 E/Zmixture of desamino huperzines (XV) which is subjected to a thiophenyl radicaladdition/elimination sequence to give a 1:1 mixture of the geometric isomers(XV). The C-5 heteroatom substitution of huperzine A is not prerequisitefor the inhibition of acetylcholinesterase. Derivatives (XIX) and (XX) revealinhibition constants in the low micromolar range, thus displaying better resultsthan 5-fluoro or 5-hydroxy derivatives. — (HOEGENAUER, KLEMENS;BAUMANN, KARL; ENZ, ALBERT; MULZER, JOHANN; Bioorg. Med.Chem. Lett. 11 (2001) 19, 2627-2630; Inst. Org. Chem., Univ. Wien, A-1090Wien, Austria; EN)

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