Totalsynthese des Naturstoffes Leustroducsin B
Final Report Abstract
As summary it must be stated that a route to the right-hand fragment cis-vinyhodide cycloheyxl ester or iodoalkyne cyclohexyl ester was elaborated. Key steps are the (S)-5-pyrrolidin-2-yl-lH-tetrazole mediated enantioselective organocatalytic Michael addition and the TPAP-mediated Nef reaction. This route offers the possibility to install either a cisvinyliodide or a iodoalkyne for a further Sonogashira coupling or a Cadiot-Chodkiewicz coupling to the left-hand fragment alkynol respectively. This sequence is much shorter as all previous reported syntheses of other comparable building blocks for the total synthesis of leustroducsin B. Preliminary investigations of both coupling methods were carried out and are very promising. In order to shorten the synthesis of the polyhydroxylated left-hand fragment of leustroducsm B the aza-Claisen rearrangement of a BDA-protected glyceraldehyde enamine was investigated and as a result a shortened route towards the versatile BDA-protected allyl-modified aldehyde was developed. The steps to this aldehyde and the following steps of stereoselective Zn-mediated aldol reaction and stereoselective transfer hydrogenation have been transferred successfully to a large scale. Further investigations of possible reactions with the BDA-protected enamine led to the C-alkylation of these substrates. By using this, a quaternary center and a variety of functionalities at the C-2 position of the BDA-protected glyceraldehyde derivative were installed in good yields and high diastereoselectivities. Furthermore, these reactions are the first examples for the C-alkylation of heteroatom substituted enamines and the first examples of stereoselective reactions with glyceraldehyde enamines.
