Crystal Structure and Chirality of the Ansamycin Antibiotic Actamycin

Abstract

The structure of the title compound has been determined from diffractometer data recorded, initially, at 294 K and, subsequently, at 168 K. Crystals are triclinic, space group P1 with (168 K values in square brackets) a 16.080(2) [15.934(2)], b 15.958(2) [15.880(2)], c 8.443(2)Ǻ [8.233(1)Ǻ], α 85.55(1) [86.04(1)],β 82.65(1) [82.56(1)],γ 85.00(1)° [84.73(1)°], and contain two actamycin and two solvent ( tetrahydrofuran ) molecules in the asymmetric scattering unit. The structure was solved with DIRDIF and refined by block-diagonal least-squares analysis (of 168 K data) to R 0.049 ( wR 0.069) for 5640 reflections and 940 refined parameters. Molecules of actamycin (30-dechloro-2-demethyl-30-hydroxynaphthomycin A) exhibit the same relative stereochemistry (8S*,9S*,15S*,18S*,19S*,20S*) and double-bond configuration (2Z,4Z,6E,12E,16E,21E) as reported for crystalline 25-O-methylnaphthomycin A iminomethyl ether but are quite differently conformed. The two crystallographically inequivalent actamycin molecules in the present structure also exhibit substantial conformational (torsion angle) differences due, apparently, to the effects of intermolecular hydrogen bonding. Consideration of chiroptical data defines the absolute configuration of actamycin as 8S,9S,15S,18S,19S,20S and the helicity as P, as in naphthomycin A.