Mycinamicins, new macrolide antibiotics. VIII. Chemical degradation and absolute configuration of mycinamicins.

Mycinamicins, a new family of basic 16membered macrolide antibiotics were produced by Micromonospora griseorubida sp. nov. They consist of at least seven components, named as mycinamicin I (1), 11 (2), III (3), IV (4), V (5), VI (6) and VII (7), and possess strong antibacterial activity against Gram-positive bacteria1-4). In an earlier study, the structures and stereochemistry of mycinamicins were elucidated on the basis of spectroscopic data, a few chemical degradations and an X-ray crystal structure analysis of mycinolide IV (8), which was an aglycone portion of 45). Recently, we obtained the dedesosaminyl derivative (10) of 1 by degradative experiments6). In the present paper, we report the structural elucidation of acetyl derivative (12) of 10 by Xray analysis, and hence propose the absolute stereochemistry of mycinamicins (Fig. 1). Treatment of 1 with m-chloroperbenzoic acid in chloroform gave its N-oxide in a high yield. Upon subsequent treatment of the N-oxide with acetic anhydride in chloroform at reflux for 5 hours, compounds 9, 10 and 11 were obtained. Compound 10 was acetylated with acetic anhydride in pyridine to yield quantitatively the 5,4"diacetate (12). Compound 12 afforded the suitable crystals for single-crystal X-ray structural study by crystallization from methanol. The elemental analysis and 1H NMR spectrum suggested that the molecule crystallizes as a 1: 1