GB1049113A - Steroid glucuronides and galacturonides - Google Patents

Abstract

Novel 16a -glycuronides and 16a -galacturonides of (D 4-3-keto, D 1,4-3-keto, or D 4-[3,2-c] pyrazolo) - 11 - (keto, hydroxy or acyloxy)-17a - (hydroxy or acyloxy) - 20 - keto - 21-(hydroxy or acyloxy)-steroids of the pregnane series and their alkali metal, alkaline earth metal, ammonium, choline and basic amino acid salts are prepared by reacting the appropriate 16a -hydroxy steroids containing a 21-acyloxy group with an alkyl or aralkyl (tri-O-acyl-a -D-glucopyranosyl or galactopyranosyl bromide) uronate to form the novel corresponding alkyl or aralkyl (steroid-16a -yl tri-O-acyl-b -D-glucopyranosid or -galactopyranosid)-uronate, and hydrolysing the latter with an alkaline hydrolysing agent to remove acyl groups from the steroid nucleus and sugar-acid residue, and if desired converting the salt to the free acid or to another salt. The steroids may, in addition to the above-mentioned substituents and double bonds, contain D 6 double bonds, 6- or 9-halogen atoms and 2- or 6-methyl groups, for example. 16a -Hydroxy-21-acyloxy-steroids used as starting materials are prepared by extracting a mixture of the 16,21-diacylates and the 21-monoacylates, e.g. the di- and mono-acetates of 9a - fluoro - 11b ,16a ,17a ,21 - tetrahydroxy - 1,4-pregnadiene-3,20-dione prepared by acetylation of the tetrol, with aqueous sodium tetraborate, the diacylates being insoluble, and the monoacylates being precipitated at pH 1.2 to 2.0. Alkyl and aralkyl (tri-O-acyl-a -D-glucopyranosyl bromide)-uronates are prepared by reacting glucuronolactone with sodium alkoxides and alcohols and then acid anhydrides to give alkyl or aralkyl-tetra-O-acyl-b -D-glucopyranuronates and then reacting these with HBr. The 16a -glycuronides and -galacturonides of anti-inflammatory steroids may be made up into pharmaceutical compositions such as injectable liquids or oral preparations.