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A comparison of the molecular conformations of cortisol, 6a-fluorocortisol, 9a-fluorocortisol, and 6amethylprednisolone, as determined by X-ray analysis, is relevant for purposes of relating conformational differences and biological activity. In 9a-fluorocortisol, the A ring is bent underneath the plane of the molecule to a much greater extent than it is in cortisol, and this bend, which may result from a close nonbonded contact between the fluorine atom and the axial substituent on C(l), resembles the conformational change occasioned by 1-2 dehydrogenation. A correlation was noted between the degree of bowing toward the a face and the variation in antiinflammatory activity in this series of corticosteroids. In all six corticoids for which the 170 side chains were compared, atoms 0(20) and 0(21) are cis coplanar, and 0(20) is oriented over the D ring as predicted by Wellman and Djerassi from solution spectral analysis. Intramolecular hydrogen bonding to'the 17a-hydroxyl group is not observed, and intramolecular hydrogen bonding within the side chain, if any, is weak and of highly distorted geometry. Although the 170 side-chain conformation seems nearly invariant, a slight variation is observed in 6afluorocortisol which is the only structure in which 0(20) is involved in a hydrogen bond.

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