Intermediates for the preparation of bile acids

A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compo...

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Hauptverfasser: ACHAMPETA RATHAN PRASAD, JOHN GREGORY REID, ROY ARCHIBALD SWARINGEN JR, ROBERT M MORIARTY, AKHILA KUMAR SAHOO
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creator ACHAMPETA RATHAN PRASAD
JOHN GREGORY REID
ROY ARCHIBALD SWARINGEN JR
ROBERT M MORIARTY
AKHILA KUMAR SAHOO
description A method of the preparation of deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:said method comprising: (a) hydrogenating 9-alpha-hydroxyandrost-4-en-3,17-dione (1.0) with H2to form compound (1.1); (b) reacting compound (1.1) with acid to eliminate the hydroxy group to form compound (1.2); (c) reacting diketone (1.2) with a reducing agent to form a mixture of compounds (1.3) and (1.4); (d) reacting compound (1.3) with a two carbon olefination reagent to form (Z)-3-alpha-hydroxy-5-beta-pregna-((11),17(20)-diene (1.5); (e) protecting the free hydroxyl to give (1.6); (f) reacting (1.6) with an alkylpropionate CH2CH2C(O)OR or an alkyl acrylate CH2=CHC(O)OR, wherein R is alkyl, in the presence of a Lewis acid to form (1.7); (g) hydrogenation to give (1.8); (h) reacting (1.8) with an oxidising agent to introduce a ketone at the 12-position; (i) hydrogenation to remove the 9(11) double bond and give (2.0); (j) reacting (2.0) with a reducing agent to afford the 12-hydroxy compound (2.1); and (k) deprotecting and hydrolysing (2.1) to afford DCA. Intermediates (1.1), (1.2), (1.5), (1.6), (1.7a), (1.7b), (1.9a) and (2.0a) are claimed per se.
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subjects CHEMISTRY
METALLURGY
ORGANIC CHEMISTRY
STEROIDS
title Intermediates for the preparation of bile acids
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