C. Zorn et al., Studies on the synthesis of aza analogues of illudins by cycloadditions tohighly strained methylenecyclopropanes, J ORG CHEM, 64(21), 1999, pp. 7846-7855
A series of 3-spirocyclopropane-tetrahydropyrid-4-ones has been synthesized
by the method consisting of nitrone cycloaddition to bicyclopropylidene an
d thermal rearrangement of the adducts. Regioisomeric 5-spirocyclopropanete
trahydropyrid-4-ones and 5-spirocyclopropanedihydropyrid-4 ones were instea
d obtained by cycloaddition of nitrones and nitrile oxides, respectively, t
o methylenespiropentane, followed by thermal rearrangement. Methylenedispir
o[2.0.2.1]heptane gave, in turn, 5,6-bis(spirocyclopropane)dihydropyrid-4 T
he new compounds were prepared as simple aza analogues of the cytotoxic nat
ural products illudins and ptaquiloside in order to study their activity in
cleaving a DNA plasmid. The activities shown by several of the compounds a
re moderate, but from a comparative qualitative analysis of the results a u
seful structure-activity relationship for this new class of compounds could
be derived.