Crystal structure of griseofulvin

The crystal and molecular structure of griseofulvin (C₁₇H₁₇ClO₆) has been determined. The antibiotic crystallizes in space group P4₁, with a=8.967(2), c=19.904(9) Å and Z=4. The structure was solved by direct methods and refined to an R value 0.056. The 3-carbonyl and 6′-methyl groups are cis, confirming Macmillan's assignment of stereochemistry. The molecular conformation is significantly different from that of the 5-bromo derivative. The methoxy substituents on the benzene ring are coplanar with the ring rather than clinal to it as in the 5-bromo derivative. The five-membered ring is only slightly puckered and the cyclohexanone ring has a half-chair conformation with the 6′-methyl group oriented over the five-membered ring to a greater extent in griseofulvin than in the 5-bromo derivative.