Scorodonin

Naturally occurring conjugated allenynes are of general interest owing to their potent and various biological activities. The 1,5-H transfer of alka-1,4-diyn-3-yl amines would be one of the most straightforward yet challenging approaches to such compounds since, in principle, two regioisomers may be formed involving two C-C triple bonds. Herein, a catalytic recipe of copper halides with mixed oxidation states, i.e., CuCl/CuBr2 , has been identified to address the issues of the side reaction of conjugate addition and the selectivity of 1,5-H transfer of alka-1,4-diyn-3-yl amines in EATA (enantioselective allenation of terminal alkynes) reaction involving 2-alkynals. This method provided various allenynes with excellent enantioselectivities, and was also applied to the first highly enantioselective total synthesis of natural product scorodonin. Mechanistic studies and DFT calculations elucidated the regioselectivity for the observed 1,5-H transfer.

The structure proposed for scorodonin, a natural allenyne with significant antibacterial and antifungal activities, was synthesized through an enantioselective route. The spectroscopic data of the synthetic allenyne are generally consistent with those reported for the natural one, but slight yet definite differences were observed in (13)C NMR.

Scorodonin (1), a novel biologically active metabolite, was isolated from submerged cultures of the mushroom Marasmius scorodonius (FR.) FR. Its structure has been determined by chemical and physical methods. The antibiotic inhibits the growth of bacteria, yeasts, and filamentous fungi. In cells of the ascitic form of EHRLICH carcinoma the incorporation of thymidine and uridine into DNA and RNA is strongly inhibited by scorodonin whereas the incorporation of leucine into protein is not affected.