Structural elucidation of aculeximycin. IV. Absolute structure of aculeximycin, belonging to a new class of macrolide antibiotics.

Abstract

Aculeximycin (1) produced by Streptosporangium albidum possesses a 30-membered polyhydroxy macrocyclic lactone and five sugars including aculexitriose. We have described the determination of the planar structure of N-diacetylated aculeximycin (2) using degradation products, which were obtained by DBU-methanol treatment, ozonolysis and periodative oxidation. In order to determine the relative and absolute configurations of aculeximycin, first, the relative and absolute configurations of the degradation products 10, 11, 12 and 13 were determined. Rychnovsky's method was very useful to determine the relative configurations of these degradation products, and CD exciton chirality and the modified Mosher's methods were applied to determine their absolute configurations. From these results, fourteen out of the twenty asymmetric centers in aculeximycin were determined to be 5S, 17R, 20S, 21R, 23R, 24R, 29S, 30R, 31S, 34R, 35S, 36S and 37R. The absolute configurations at C-14 and C-15 on the hemiketal ring were confirmed using 12 obtained by the partial glycol bond cleavage of 9. Absolute configurations of the remaining asymmetric centers were determined by spectral analysis of 15 and NOE experiment on 1. From these results, the absolute configuration of 1 was determined to be 5S, 7R, 10S, 11R, 14R, 15S, 17R, 19R, 20S, 21R, 23R, 24R, 25S, 29S, 30R, 31S, 34R, 35S, 36S and 37R.