STUDIES IN SYNTHESIS OF VERNOLEPIN - DIELS-ALDER APPROACH TO ANGULARLY FUNCTIONALIZED AB SYSTEM

In model systems it was demonstrated that the sequence osmium tetroxide-barium chlorate, lead tetraacetate-methanol-benzene and lithium tri-tert-butoxyaluminum hydride may be used to convert conjugated cyclohexenones to valerolactones with excision of the .alpha.-carbon of the enone. A regiospecific and stereospecific Diels-Alder reaction of 2-methoxy-5-hydroxymethyl-1,4-benzoquinone with 1-methoxy-1,3-butadiene gave 2,8.beta.-dimethoxy-4a.alpha.-hydroxymethyl-5,8.alpha.-dihydronaphthalene-1,4-(8a.alpha.H,4aH)-dione. This was converted in 5 steps to 2.beta.-formyl-2.alpha.-acetoxymethyl-4.alpha.,5.alpha.-oxido-6.beta.-methoxycyclohexane-1.beta.-acetic acid methyl ester. Treatment of the latter with lithium tri-tert-butoxyaluminum hydride gave a 19% yield of 8a.alpha.-acetoxymethyl-5.beta.-methoxy-6.alpha.,7.alpha.-oxido-4a.alpha.-2-oxa-3-decalone and a 46% yield of 4-acetoxymethyl-6-exo-methoxy-7-endo-hydroxy-2-oxabicyclo[3.2.1]octane-2-exo-acetic acid methyl ester. The stereochemistry of all intermediates and products was proven by taking advantage of intramolecular reactions. Vernolepin is used as a tumor inhibitor.