Tetrahedron Leaers.Vol. 35, No. 9, pp. 1367-1370.1994 Elsevier Seiatce L&l RintiillGRAtBritsill oo40-4039194 56.cloiO.00 0040-4039(94)EOO35-V zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML A Total Synthesis of the Sesqaiterpene Qainone Metachromin-A Wanda P. Almeidaa and Carkos Roqoe D. Cox~&b * a Instituto de Qufmica. Universidade Federaldo Rio de Janeim, RJ. 21945-970. Brasil b Institute de Qufmica , UniversidadeEqtadual de Campiaas, Campinas, SP, 13081~!ZO, Brasi zyxwvutsrqponmlkjihgfed Abrtructs: The first total synthesis of the marine natural product metaehromin A was -mpltshed Uuough a convergent synthesis amenable to the pnqaration of synthetic analogues. The main features of this synthesis are the introduction of the oxygenation at Cl7 employing a Thiele acetoxylation reaction and a stereoeekctive Horner- Wadsw@-Emmons coupling of a mmstabilized phosphonatewith a methyl ketone derivative to generatethe required (E)-ttisuhstituted douMebond. The search for biologically active natural products from mtine organisms has been an intense scientific activity in the last two decades that has provided promising new leads for therapeutical investigations.’ The recently discovered sesquiterpene quinones isolated from marine sources constitute a new and fascinating family of natural compounds possessing a diverse biological activity profile, making them valuable targets in medicinal chemistry.2 Recently, Kobayashi and collaborators repo&d the isolation and structure elucidation of eight new, biologically active, sesquiterpene quinones from the purple-colored Okinawau marine sponge Hippos~ongiu zyxwvutsrqpo metachromia. 3 These were named metachromins A-H featuring au unusual carbon skeleton with few precedents in the literature. More importantly, metachromiu A and B exhibited potent sntineoplastic activity associated with a remarkable coronary vasodilating activity. This dual biological characteristic of these new quinones makes them very attractive as synthetic targets and we herein report the first total synthesis of (+I-)meta&romin A (l), the most abundant and one of the most active of the metachromins, employing a flexible and convergent synthetic strategy suitable for the preparation of synthetic analogues. The synthetic strategy was centered on a disconnection at the trisubstituted double bond between CpClo (figure), which generated two key fragments, the unsaturated ketone 2 and the aromatic phosphonate 3, that could be coupled by means of a Homer-Wadsworth-Es (HWB) reaction to construct the basic skeleton of the metachromins. Figure: The Synthesis Plan. &la = = 1 (Metachromin A) 2 1367