GB1436549A - 17beta-mercaptocarbonyl-3alpha-hydroxy-steroids and their esters - Google Patents

Abstract

1436549 17#-Mercaptocarbonyl-3α-hydroxy steroids and their esters GLAXO LABORATORIES Ltd 15 June 1973 [15 June 1972] 28117/72 Heading C2U Novel steroids of the androstane and estrane series possess a 3α-hydroxy group, a 5α- hydrogen atom or a 4,5-double bond, a 17α- hydrogen atom and at the 17#-position a -COSH or esterified -COSH group. They may be prepared by (a) reacting 17#-carboxy steroids or reactive derivatives thereof with appropriate reagents, e.g. H 2 S or RSH (R is an aliphatic, cycloaliphatic, aryl or C-attached heterocyclic group); (b) for the esters, esterification of the free acids; or (c) stereospecific reduction of the corresponding 3-ones. In processes (a) and (b) the 3α-OH group may be protected, e.g. by esterification, particularly as a nitrate ester, and subsequently released. Products may be interconverted, e.g. a halogen in the group R may be replaced by an amino group and substituents and double bonds may be introduced into the steroid ring system, and when they contain a basic group they may be converted into salts. 2# - ethoxy - 3α - nitro - oxy - 5α - androstan- 11 - one - 17# - carboxylic acid chloride: and 3α - nitro - oxy - 11 - oxo - 5α - androstane - 17#- carboxylic acid chloride are prepared from the free acids and oxalyl chloride. 17#-(2<SP>1</SP>-morpholinoethylthiocarbonyl)- 3α - nitro - oxy - 5α- androstan-11-one is prepared from the 17#- chlorocarbonyl compound and morpholinoethane thiol; 17#-methylthiocarbonyl-3α-nitrooxy - 5α - androstan - 11 - one is prepared similarly and 17# - (2<SP>1</SP> - chloroethylthiocarbonyl)- 3α - nitro - oxy - 5α - androstan - 11 - one is prepared from the 17#-chlorocarbonyl compound and thiurane. 3α - Nitro - oxy - 11 - ozo - 5α- androstane - 17# - carboxylic acid is prepared by nitration of the 3α-ol (prepared in turn by NaOBr oxidation of 3α-hydroxy-5α-pregnane- 11,20-dione). The novel steroids have anaesthetic properties and they may be made up into anaesthetic compositions with suitable carriers.