Quantitative Analyses of Biochemical Kinetic Resolution of Enentiomers

Article abstract of DOI:10.1021/ja00389a064

Equations and useful graphs for the quantitative treatment of biochemical kinetic resolution data have been developed.These expressions have been verified experimentally, and they possess predictive values in relating the parameters of the extent of conversion of racemic substrate (c), the optical purity expressed as enantiomeric excess (ee), and the enantiomeric ratio (E). formation draws the C(18) methyl away from D ring.The two conformers must be in equilibrium in solution.Both molecules of 18-deoxyaldosterone resemble aldosterone in the overall shape of the A, B, C, and E rings.Molecule II and aldosterone have similar hydrogen bonding to O(3) and nearly planar 4-en-3-one conformations.Although the D-ring composition of aldosterone and 18-deoxyaldosterone is different, the side-chain orientation of molecule I of 18-deoxyaldosterone comes closest to approximating that of aldosterone in shape and potential hydrogen-bonding geometry.Analysis of the conformations and activity of aldosterone, 18-deoxyaldosterone, and spironolactone is an agreement with the model which proposes that the A-ring end of the steroid is primarily responsible for initiating and maintaining receptor binding and D-ring variation governs agonist-antagonist responce.Molecule II appears to have an A ring ideally suited to receptor binding and a side-chain orientation that would elicit little or no subsequent activity, while molecule I has the side-chain orientation that most likely contributes to the partial agonism exhibited by the molecule.The crystal structure of the hemihydrate of 18-deoxyaldosterone (a = 19.878(3) Angstroem, b = 30.341(4) Angstroem, c = 5.9951(5) Angstroem, P2₁2₁2₁) was determined by direct methods and refined to a final R index of 0.072.