Generalization to the Epipolythiodiketopiperazine Alkaloids

Upon completion of the synthesis of (+)-ll,ll -dideoxyverticillin A (1), it was recognized that there were only a handful of reports of monomeric epitri- or epitetrathiodiketopiperazine syntheses, nearly all of which were accomplished with lack of sulfide chain length control. In the limited cases where selectivity was achieved, the results were highly substrate dependent or the method lacked substrate scope [56], 

The key precept for any strategy would involve complete stereochemical control and precision in the degree of sulfidation. Accordingly, we envisioned that the epipolysulfides could arise from the ionization of a C15 hemiaminal derivative and subsequent cyclization of a polysulfane onto the resultant /V-acyliminium ion. The polysulfane would be derived from the corresponding thiol accessed by regioselective functionalization of the Ca(Trp) position. 

Hauser D, Weber HP, Sigg HP (1970) Helv Chim Acta 53 1061 

Katagiri K, Sato K, Hayakawa S, Matsushima T, Minato H (1970) J Antibiot (Tokyo) 23 420 

Saito T, Suzuki Y, Koyama K, Natori S, Iitaka Y, Knoshita T (1998) Chem Pharm Bull 36 1942 

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