Crystal and Molecular Structures of Two Isomorphous Solvates of the Macrolide Antibiotic Borrelidin: Absolute Configuration Determination by Incorporation of a Chiral Solvent in the Crystal Lattice

Abstract

Crystal structures of two isomorphous solvates of the macrolide antibiotic borrelidin [ borrelidin 3-methylbutan-1-ol (A) and borrelidin (S)-2-methylbutan-1-ol (B)] have been determined from X-ray diffractometer data recorded at 294 and 152 K respectively. Crystals are monoclinic, space group P2₁, with a 13.501(2), b 12.000(2), c 11.863(2) Å , β 110.76(1)º [(A); T = 294 K], and a 13.565(2), b 11.646(2), c 11 .376(3) Å, β 109.76(1)º [(B); T = 152 K], (Z = 2). The structures were solved by direct-methods procedures and refined by full-matrix least-squares analysis to conventional R-factors of 0.061 [(A), 2676 reflections] and 0.048 [(B), 2851 reflections]. The absolute configuration of borrelidin follows from the known chirality of the (S)-2-methylbutan-1-ol solvent in (B), and is 3S,4S,6S,8R,1OS,11R,17S,18R,22R. The unusual structural and stereochemical features of borrelidin are discussed in relation to other macrolide antibiotics.