Novel transannular rearrangements of azalide iminoethers

The transannular reactions between the aglycone hydroxyl groups and the iminoether and lactone groups of the 9a- and 8a-azalide iminoethers 4 and 5 were investigated under a variety of conditions. Translactonization by the Il-hydroxyl groups of 4 and 5 were found to give the corresponding 13-membered iminoethers 21 and 9. The thermal rearrangement of 4 produced an epimeric mixture of the 9,11-iminoethers 15 and 16. Further elaboration of isomer 16 produced 8-epi azithromycin 20. Finally, we have proposed an alternative structure, the amino gamma-lactone 25, for one of the reported products (14) from the Beckmann rearrangement of erythromycin A (9E)-oxime 13. An authentic sample of 9a-aza-9a-homoerythromycin A 14 was prepared in three steps from iminoether 4. (C) 1997 Elsevier Science Ltd.