Studies of 1-cyanosteroids

Glen, Alasdair T (1965) Studies of 1-cyanosteroids. PhD thesis, University of Glasgow.

Abstract

Cyanation of 5alpha-cholest-l-en-3-one with potassium cyanide and ammonium chloride in aqueos dimethylformamide gives 1beta-cyano-5alpha-cholestan-3-one which reacts with bromine in acetic acid to give mainly 2alpha-bromo-1beta-cyano-5alpha-cholestan-3-one. Dehydrobromination of the bromoketone with lithium chloride in dimethylformamide gives l-cyano-5alpha-cholest-l-en-3-one and dehydrobromination of the mother liquors by the same method gives the same unsaturated ketone together with l-cyano-cholesta-l,4-dien-3-one and 1beta-cyano-cholest-4-en-3-one. Hydrogenation of l-cyano-5alpha-cholest-l-en-3-one in the presence of palladised charcoal gives 1beta-cyano-5alpha-cholestan-3-one. Treatment of the 1beta-cyano-ketone with bromine in acetic acid gives 2alpha-bromo-1beta-cyano-5alpha-cholestan-3-one which, when dehydrobrominated by lithium chloride in dimethylformamide also yields 1-cyano-5alpha-cholest-l-en-3-one. Both the 1beta- and 1beta-cyano-ketones are unaffected by treatment with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone in benzene and in dioxin containing a trace of hydrogen chloride. Basic hydrolysis of 1beta-cyano-5alpha-cholestan-3-one and 1beta-cyano-5alpha-cholestan-3-one gives 3alpha-amino-1beta-carboxy-3alpha-hydroxy-5alpha-cholestane lactam which forms an O-methyl derivative on treatment with methanolic hydrogen chloride. The epimerisation of the 1beta-cyano-ketone to the 1beta-cyano-ketone by the action of alkali has been demonstrated. Treatment of l-cyano-5alpha-cholest-1-en-3-one with alkali gives 5alpha-cholestan-1,3-dione. Treatment of 1beta-cyano-5alpha-cholestan-3-one with ethylene glycol and boron trifluoride etherate gives 1beta-cyano-3-ethylenedioxy-5alpha-cholestane from which the ketone may be readily regenerated. Reduction of 1beta-cyano-5alpha-cholestan-3-one with sodium borohydride or aluminium iso-propoxide in iso-propyl alcohol gives 1beta-cyano-5alpha-cholestan-3alpha-ol, from which the 3alpha-acetate was prepared, while reduction with sodium borohydride in methanol or lithium aluminium tri-tert-butoxyhydride in tetrahydrofuran gives an epimeric mixture of 1beta-cyano-5alpha-cholestan-3-ols. Reduction of 1beta-cyano-5alpha-cholestan-3-one or 1beta-cyano-5alpha-cholestan-3-ol with lithium aluminium hydride in ether yields 1beta-aminomethyl-5alpha-cholestan-3-ol which forms the 1beta-3alpha-diacetate. The diacetate is hydrolysed by aqueous mathanolic sodium carbonate to the 1beta-acetate. Both the amine and the monoacetate show evidence of intramolecular hydrogen bonding.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: J Mclean
• Keywords: Organic chemistry
• Date of Award: 1965
• Depositing User: Enlighten Team
• Unique ID: glathesis:1965-73865
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73865