Manufacture of 17ª‡:21-dihydroxy-20-ketones of the pregnane series

摘要

The invention comprises (1) a process for the preparation of 17a :21-dihydroxy-20-keto-pregnanes wherein a 21-oxygenated- D 17(20)-pregnene 20-enol ester is reacted with a complex metal hydride in a hydroxy-free solvent and in a resulting complex, if desired after destroying the excess of reducing agent by addition of a ketone, a hydroxylating metal oxide is additively combined at the 17:20-double bond and finally the addition product is hydrolyzed and, if desired, the free 21-hydroxyl group esterified; (2) steroids of the formula: wherein R1 is a ketalized oxo group and R2 and R3 are free, esterified or etherified hydroxyl groups; and (3) 21-monoesters and 18,21-diesters of 17a -hydroxy-aldosterone wherein the ester groups are derived from carboxylic acids containing up to 20 carbon atoms, with the exception of the dibenzoate. The starting materials may contain free or protected oxo groups e.g. in the 3-, 11- and/or 18-positions, free, esterified or etherified hydroxyl groups e.g. in the 3-, 6-, 11- and/or 16-positions, or methyl groups e.g. in the 2-, 6- or 16-position. 11-Keto groups may be reduced to 11b -hydroxy groups in the reduction process, and protective groups hydrolyzed during or subsequent to the hydrolysis process. Examples are given and an extensive list of esterifying acids is provided. 20-Enol esters of 20-keto-pregnanes used as starting materials may contain in the 21-position a free or esterified hydroxyl group or at the 20-carbon atom an aldehyde group or a free or esterified hydroxyl group. The 20-one-21-ols are prepared from the 21-ols, for example by oxidation with cupric acetate, and are converted into the 20-enol acetates, for example, by glacial acetic acid-pyridine-acetic anhydride. The 20-enol esters having an ester group in the 21-position may be obtained by catalytically hydrogenating a D 1 6-20-oxo-pregnane 21-acid ester in a neutral medium and then acylating the D 17(20)-20-hydroxy-pregnane-21-acid ester.