Abstract
The first total synthsis of pyridomycin (1) is described, in which the construction of the exocyclic (Z)-s-butylidene moiety in the 12-membered ring system of 1 was well achieved through an efficient stereocontrolled route. Following a straightforward preparation of the linear azido carboxylic acid 14 from the three subunits 4,5 and 6, the 12-membered ring compound 15 was synthesized by reduction of the azido group and DCC-HOBt cyclisation of the resulting seco-amino carboxylic acid. Dehydration and ozonolysis of 15 gave the key intermediate 3. Stereo-controlled construction of the exocyclic (Z)-s-butylidene side chain of 1 was achieved by lithium dimethylcuprate coupling to the enol phosphate of 3 under the modified Weiler's conditions. The resulting 2d was transformed into pyridomycin (1) by three-step manipuration including the introduction of the hydroxypicolinyl moiety.
