A One-Pot Condensation of Pyrones and Enals. Synthesis of 1<i>H</i>,7<i>H</i>-5a,6,8,9-Tetrahydro-1-oxopyrano[4,3-<i>b</i>][1]benzopyrans

Abstract

Condensation of various 6-substituted 4-hydroxypyrones 1 with 1-cyclohexenecarboxaldehydes in the presence of l-proline in ethyl acetate gave high yields of substituted 1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyrans. The reaction presumably occurs via the 1,2-addition of the pyrone with the aldehyde followed by dehydration and then cyclization through a 6Π electrocyclic process. A remarkable asymmetric induction was obtained from a stereogenic center (C4) of the cyclohexenecarboxaldehyde [such as (S)-perillaldehyde] to provide only the C5a,7-trans tricyclic pyrone products. On the other hand, condensation of 3-(formyloxy)- or 3-hydroxy-2-methyl-1-cyclohexenecarboxaldehydes with pyrones 1 gave mixtures of C5a,6−cis and -trans products. Several of the tricyclic pyrones strongly inhibit acetylcholinesterase activity, DNA synthesis, and tumor cell growth in vitro.