Absolute configurations of Emycin D, E and F; mimicry of centrosymmetric space groups by mixtures of chiral stereoisomers

The crystal structures of Emycin E (1), di-o-bromobenzoyl-Emycin F (2) and o-bromobenzoyl-Emycin D (3) have been determined by X-ray analysis at low t emperature. Emycin E and o-bromobenzoyl-Emycin D both crystallize with two molecules in a triclinic unit cell. These two structures can be solved and refined either in the centrosymmetric space group P (1) over bar, with appa rent disorder localized at or around the expected chiral centre, or in the non-centrosymmetric space group P1 as mixtures of two diastereomers without disorder. Only the latter interpretation is consistent with the chemical a nd spectroscopic evidence. Refinements in the centrosymmetric and non-centr osymmetric space groups are compared in this paper and are shown to favour the chemically correct interpretation, more decisively so in the case of th e bromo derivative as a result of the anomalous dispersion of bromine. Stru ctures (1) and (3) provide a dramatic warning of the dangers inherent in th e conventional wisdom that if a structure can be refined satisfactorarily i n both centrosymmetric and non-centrosymmetric space groups, the former sho uld always be chosen. In these two cases, despite apparently acceptable int ensity statistics and R factors (5.87 and 3.55%), the choice of the centros ymmetric space group leads to the serious chemical error that the triclinic unit cell contains a racemate rather than two chiral diastereomers! The we akest reflections are shown to be most sensitive to the correct choice of s pace group, underlining the importance of refining against all data rather than against intensities greater than a specified threshold. The use of sim ilar-distance restraints is shown to be beneficial in both P1 refinements. Di-o-bromobenzoyl-Emycin F crystallizes in the monoclinic space group P2(1) with one molecule in the asymmetric unit and so does not give rise to thes e problems of interpretation. The absolute configuration of the two bromo d erivatives, and hence the Emycins in general, was determined unambiguously as S at the chiral centre C3.