Synthesis of saframycins. XII. 1 total synthesis of (-)- N-acetylsaframycin Mx 2 and Its epi-(+)-enantiomer

• Published in: Tetrahedron 1995-07, Vol.51 (30), p.8231-8246
• Main Authors: Saito, Naoki, Harada, Shunji, Inouye, Izumi, Yamaguchi, Kentaro, Kubo, Akinori
• Format: Article
• Language: English
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/0040-4020(95)00436-C

The first total synthesis of (-)-N-acetylsaframycin mx 2 ( 1c) from (±)-pentacyclic amine 10b is described. The reaction of 10b with Cbz-L-alanine gave an inseparable mixture of amides 11b and 14b. Deprotection of the Cbz group to amines 11b and 14b followed by treatment with acetic anhydride in pyridine produced amides 13b and 16b. The structure of 16b was determined by X-ray crystallography. The conversion of 13b to the bisquinone 20 and subsequent stereoselective and regioselective introduction of the methoxyl group at position 5 provided 22. Finally, 22 was subjected to catalytic reduction and regioseleclive oxidation to give 1c. On the other hand, the epi-emantiomer 16b was transformed to 27 in a same four-step sequence. The specific optical rotation and the CD spectra of 1c and 27 were of opposite sign. The assignment of the absolute configuration of saframycins mx as 5S,6R,9R, 14aS,15R,19S is also discussed.