The Biomimetic Synthesis of Acetogenin Isoquinoline Alkaloids

Condensation of acetone with the protected ester 44 yielded the monoketalized triketone 45, which, after transformation into its dianion, was further condensed to 46. This, however, failed to give the resorcinol 48. The two sterically and electronically inactivating ethylene ketals completely prevented cyclization reac- 

Neither 30 nor any of the terminally protected polyketones 46, 51, or 55 could be used as a basis for a total synthesis of naphthyl isoquinoline alkaloids. Synthetic efforts thus focused on a derivation of the central carbon atom of the polycarbonyl chain (54-56). 

The central ketal function, which electronically and sterically governed the 

The key step of the other synthesis was C-acetylation of aryl propanones like 72, which are readily accessible from the corresponding benzaldehydes 71. This aryl propanone route was very effective for the synthesis of /sphenolic diketones like 70 (X = OR), thus ideally complementing the other route. Both methods also allowed the synthesis of the free diketone 31 (70, R = H, X = OH) with two unprotected phenol functions in the aromatic ring, which could not be prepared by 0-dealkylation of the hydroxyethyl ether 58, as obtained in the biomimetic syntheses. 

Naphthalenes and Isoquinolines from Joint Biosynthetic Precursors 

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