Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)3 chemistry

The total synthesis of a racemic analog of putative helioporin C has been achieved. Starting from eta(6)-5.6-dimethoxyretralin-Cr(CO)(3) the target molecule was obtained in 8 steps in an overall yield of ca. 17%. The synthesis is based on the specific reactivity and stereochemistry of the arene-Cr(CO)(3) substructure and involves highly regio- and diastereoselective benzylic deprotonation/alkylation steps. The sidechain stereocenter was diastereoselectively established under substrate control by Michael addition of a benzylic lithiated complex to ethylidene Meldrum's acid. The relative configuration of the addition product was confirmed by X-ray crystal structure analysis. By correlation of NMR spectroscopic data of the marine diterpene helioporin C with a number of stereochemically defined synthetic analogs it was shown that the original stereochemical assignment for this compound has to be revised. The configuration of helioporin C (23) was established to be identical with that of the seco-pseudopterosins. (C) 1999 Elsevier Science Ltd. All rights reserved.