Saframycin Mx 2 4b was discovered in the culture broth of the myxobacterium, Myxococcus xanthus in 1988. It is interesting that this compound has a quinone moiety on the E-ring and a hydroquinone, because the only successful total synthesis within the saframycin family has been of the bisquinone series. We describe first the transformation of (-)-saframycin A 1a to the saframycin Mx type compound (-)-15 and the synthesis of saframycin E 1e, whose structure has not yet been established because of its instability, from saframycin B 1b. Next, we described the first total synthesis of (-)-N-acetylsaframycin Mx 2 25a from (±)-pentacyclic amine 17, which was a key intermediate of our (±)-saframycin synthesis. The reaction of 17 with Cbz-L-alanine gave a mixture of amides (-)-18a and (-)-18b. Deprotection and acetylation of (-)-18a and (-)-18b produced amides (-)-20a and (-)-20b, respectively. The structure of (-)-20b was determined by X-ray crystallography. The conversion of (-)-20a to the bisquinone (-)-21a and subsequent stereoselective and regioselective introduction of the methoxyl group at position 5 provided (-)-22a. Finally, (-)-22a was subjected to catalytic reduction and regioselective oxidation to give (-)-25a in modest yield. The epi-enantiomer (-)-18b was transformed to (+)-25b in a same four-step sequence. The specific optical rotation and the CD spectra of (-)-25a and (+)-25b were of opposite signs.
