Scytoneman-2,20-dione 13 was obtained directly from the corresponding reduced dimer 12a by oxidation with DDQ. To obtain scytonemin, the methoxy functionalities of 12b had to be converted into its corresponding hydroxyl groups before oxidation. Employing standard Lewis acidic demethylating conditions afforded the wanted conversion into tetrahydroscytonemin 12c, albeit with a moderate decay of the substrate. Utilizing the oxidizing properties of DDQ in the last synthetic procedure provided scytone- min (1). Interestingly, reversing the order of the two last synthetic operations, and thus demethylating the methoxy scytonemin analogue, yielded no product at all. It has previously been reported that scytonemin is sensitive toward alkaline and Brønsted acidic conditions,20 a list which now can be supplemented with Lewis acidic condi- tions. The sensitivity to basic conditions impeded our initial plan to use a silyl protective group on the phenolic oxygen and then remove both this and the vinylic TMS group at the same time in a final global deprotection. Despite several attempts, we failed to develop reaction conditions strong enough to enforce excision of the vinylic TMS group but mild enough not to cause decomposition of scytonemin or its tetrahydro analogue. (20) Garcia-Pichel, F.; Castenholz, R. W. J. Phycol. 1991, 27, 395. In summary, we have completed the synthesis of the cyanobacterial alkaloid scytonemin. The parent struc- ture, the scytoneman skeleton, was assembled by a ferric chloride induced oxidative coupling of two iden- tical fragments. This tetracyclic fragment was effec- tively constructed stereospecifically, with respect to the exocyclic double bond, by a tandem Heck Suzuki Miyaura cyclization as a key reaction. The synthetic route is flexible and allows for effective synthesis of numerous scytonemin analogues. We anticipate that this could pave the way for the scytoneman skeleton as a lead structure in the development of new anti- inflammatory and anticancer drugs and potentially also new UV stabilizers. Acknowledgment. We thank the Swedish Research Council and the Centre for Skin Research at University of Gothenburg for financial support. Supporting Information Available. Experimental pro- cedures are supplied for all compounds, characterization data and NMR-spectra are supplied for key compounds. This material is available free of charge via the Internet at http://pubs.acs.org. Org. Lett., Vol. 13, No. 16, 2011 4461