Tin-mediated esterification in macrolide synthesis

Article abstract of DOI:10.1021/ja00362a018

A neutral and relatively simple new method for effecting internal macrocyclic esterification of omega -hydroxycarboxylic acids, based on a tin 'template-driven' extrusion process, is discussed and its application to the synthesis (macrocyclization step) of the macrolide antibiotics zearalenone, ingramycin, and nodusmicin detailed. An efficient, formal total synthesis of pyrenophorin using this technique is also presented. Attempts to extend the methodology to include the macrocyclization of omega -bromo carboxylic acids or omega -mercapto carboxylic acids were unsuccessful. However, although beta - and omega -amino carboxylic acids preferentially gave way to polymer formation, 4-,5, and 6-amino carboxylic acids readily condensed to give the corresponding five-, six-, and seven-membered lactams in excellent yields. For example, in this way, the bridged lactam 1-azabicyclo- left bracket 3. 3. 1 right bracket nonan-2-one was prepared in 77% yield as compared to the previously reported yield of less than 2%.