title: Asymmetric reduction of steroidal 20-ketones: chemical synthesis of corticosteroid derivatives containing the 20 alpha, 21-diol and 17 alpha, 20 alpha, 21-triol side chains.
abstract: A method is presented for the chemical synthesis of corticosteroid derivatives containing the 20 alpha, 21-diol and 17 alpha, 20 alpha, 21-triol side chains. The ketol side chains of cortisol, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone were reduced at C-20 with sodium borohydride in a two-phase system consisting of aqueous calcium chloride and an organic phase of chloroform or ethyl acetate. Stereoselectivity of reduction was 92% alpha-oriented for cortisol and 79% alpha-oriented for 11-deoxycortisol at -27 degrees. The 20 alpha-form diminished relative to the 20 beta-form with increasing temperature. For the 17-deoxy steroids, reduction to the 20 alpha-form was 23% for 11-deoxycorticosterone and 41% for corticosterone. The 20 alpha/20 beta ratios of 17-deoxy steroids were unchanged between 0 degree and -27 degrees. Calcium ions increased the solubility of corticosteroids in the aqueous phase. We propose that calcium ions affect the stereochemistry of reduction by forming a bidentate complex with the side chains of 17 alpha-hydroxy steroids, fixing them in an orientation favorable to 20 alpha-reduction, and by altering the phase partition of the steroids.
mesh_terms: D001894:Borohydrides; D002122:Calcium Chloride; D055598:Chemical Phenomena; D002621:Chemistry; D003345:Corticosterone; D003350:Cortodoxone; D003900:Desoxycorticosterone; D005938:Glucocorticoids / Q000138:chemical synthesis*; D006854:Hydrocortisone; D010084:Oxidation-Reduction; D012995:Solubility; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D001894:Borohydrides; D005938:Glucocorticoids; D003900:Desoxycorticosterone; C025364:sodium borohydride; D002122:Calcium Chloride; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone