Totalsynthese der Mansouramycine A-E aus Streptomyces sp. und Rhodium-katalysierte 1,2-Additionen an cyclische Enone

The following thesis is divided into two sections. The first part deals with the total synthesis of Mansouramycin A-E. The second part shows a new high enantioselective rhodium catalyzed 1,2-addition of aluminum-organyles to cyclic enones and en-1,4-diones. The Mansouramycines where isolated in the Laatsch group at the department of Chemistry in Göttingen. They show a high cytotoxicity against many human cancer cell lines with an IC50 up to 0.089 μM for lung cancer. The total synthesis started with a Henry reaction of a 2,5-dimethoxybenzaldehyde to give after reduction the corresponding amine. This was cyclized by a Pictet-Spengler reaction and oxidized at palladium to give the isochinoline. After oxidation with CAN the resulting chinolindione was selectively aminated to give the corresponding Mansouramycine in a total yield of 7-32%. A high enantioselektive rhodium catalyzed 1,2-addition of aluminum organyles to cyclic enones and en-1,4-diones was developed in the Zezschwitz group at the university of Marburg. In this thesis a new [Rh(cod)OMe]2 catalyzed 1,2-adition containing (R)-BINAP and different aluminium organyles to cyclic en-1,4-diones was found. The corresponding tertiary alcohols where isolated with an ee up to 98%. The diones could be functionalized at both centres without any 1,4-additions and yields from 40-90% where optained.