STEREOSELECTIVE SYNTHESIS OF RACEMIC ELEMANOLIDE DILACTONES RELATED TO VERNOLEPIN

A synthesis of 8-deoxy-9β-hydroxyvernolepin (16), an isomer of the elemanolide sesquiterpene dilactone vernolepin, is described. The synthesis employs the monoketal of 1, 4-cyclohexanedione as the starting point and proceeds via symmetrical intermediates. Introduction of the requisite acetic acid side chains is achieved via symmetrical dialkylation of the enamine derivative of the aforementioned ketone using l, 3-dichloro-2-propene as an acetic acid chloride equivalent. The second (ketal protected) carbonyl grouping is employed to introduce the geminal hydroxymethyl, vinyl substituents after reduction and protection of the 4-ketone grouping. This is accomplished by carbethoxylation and alkylation of the resulting β-keto ester enolate with ethyl iodoacetate to give a single keto diester of the proper relative stereochemistry at the four contiguous chiral centers. The stereochemistry was confirmed through conversion of this intermediate to bisnordihydro-8-deoxy vernolepin (21), a substance of known stereochemistry. © 1979, American Chemical Society. All rights reserved.