Chimeric Azalides with Functionalized Western Portions

Abstract

A series of chimeric azalides which are homologous to the potent azalide antibiotic 9-deoxo-8a-aza-8a-homoerythromycin A (2) in their eastern halves, but which have functionally complex western halves derived from a variety of sources, including carbohydrates, is reported.The erythromycin derived azalide antibiotics, the prototypes of which are 9-deoxo-9a-am-9a-methyl-8ahomoerythromycin A (1) and 9-deoxo-&-aza-8a-methyl-8a-homoerythromycin A (2), combine the safety of erythromycin with an expanded gram negative spectrum and wider tolerance to oral administrati~n.~In a previous report, we described the conversion of the erythromycin-derived acyclic fragment (3) to a class of "chimeric" azalides2 which have eastern portions corresponding to those found in 1 or 2, but which have western portions (represented by " A in the figure) simplified to a chain of methylene groups.3We now report the extension of our "cut and paste" method to the synthesis of chimeric 8a-azalides with more highly functionalized western portions (4) H ~N 3 ' HOh.&"chimeT annelati