16a-dicarbomethoxymethyl steroids and the photo-oxygenation of steroidal enol acetates

Sleigh, Thomas (1962) 16a-dicarbomethoxymethyl steroids and the photo-oxygenation of steroidal enol acetates. PhD thesis, University of Glasgow.

Abstract

The first part of this thesis describes the preparation of 3-hydroxy-11,20-dioxo-5a-pregnan-16a-ylmalonic acid, by the Michael addition of diethyl sodio. malonate to 3-acetoxy-5a-pregn-16-ene-11,20-dione, in the presence of an excess of diethyl malonate, and brief alkaline hydrolysis of the product. When the reaction was carried out with approximately equal molecular quantities of sodium and diethyl malonate the product was 3-hydroxy-16a,24-cyolo-21-norcholan-11,20,23-trione. The Michael reaction between 3-actetoxy-5a-pregn 16-ene-11,20-dione and diethyl sodiomethylmalonate gave, after hydrolysis, a mixture of the desired acid and a cyclonoroholantrione, but carrying out the reaction with dimethyl sodiomethylmalnata and chromatography of the product gave pure dimethyl (3-hydroxy-11,20-dixo-5a-pregnan-16 -mcthylmalmat. It has not been found possible to prepare a 17a-hydroxy-16-dioarbomethoxymethyl compound or to carry out a Michael reaction between 3-acetoxypregaa-5,16-dien-20-one oxime and diethyl sodiomaionate. The second part of the work is mainly concerned with the photochemical oxygenation of three steroidal end l acetates and the identification of the products. Photo-oxygenation of 3-acetoxyergosta-3,5,7,9(11),22-tetraene gave 3-aoetoxyergosta-3,5,7,9(11),22.pentaene, 3-acetoxy-5a,8a-epidioxyergosta-3,6,22-triene and 3-acetoxy-5, 14-dihydroxyergosta-3,8(9),22-trien-7-one. On treatment with alkali, the epidioxide underwent saponfloation accompanied by a novel re-arrangement to give 4-hydroxyergosta-4,6,8(14)22- tetraen-3-one. Treatment of the epidioxide with sodium borohydride gave, depending on the solvent used, various compounds which were not identified, and catalytic hydrogenation gave a mixture of diols or triols, which could not be separated to give any pure compound. Chromium trioxide-pyridine oxidation of ergosterol peroxide gave 5a,8a-epidioxyergosta-6,22-dien-3-one. which on alkali treatment gave 4-hydroxyergosta-4,6,8(14),22-tetraen-3-one. Alkali treatment of 3-acetoxy-5 14-dihydroxyergosta-3,8(9),22-trien-7-one gave 7,14-dihydroxyergosta-4,6,8(9),22-tetraan-3-one. Aerial oxidation of ergosta-4,6,22-trien-3-one in alkaline medium did not give the expected 4-hydroxy ergosta-4,6,8(14),22-tetraen-3-one, but the 4-hydroxy 4,6,22-trien-3-one. Ergosta-4,6,8(14),22-tetraen-3-one, under the same conditions, gave 4-hydroxyergosta-4,6,8(9),14,22-pentaen.-3-one. Photo-oxygenation of 3-acetoxyergosta-3,5,7,9(11),22- pentaene gave 3-acetoxy5a,8a-epidioxyergosta-3,6,9(11), 22-tetraene as the sole crystalline product. Treatment of this epidioxide with alkali yielded 4-hydroxyergosta-4,6,8(14),9(11),22-pentaen-3-one. 3-Acetoxylumista-3,5,7,9(11),22-pentaene was the only crystalline material obtained by photo-oxygenation of 5-acetoxy 1umista-35,7,22-tetraene. Examination of the mother liquors from the crystallisation of ergosteryl acetate peroxide has revealed that 3? -acotoxyergosta-5,8(9),22-trien-7-one is produced as a byproduct during the photo-oxygenation of ergosteryl acetateo but no dehydroergosteryl acetate was obtained.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: P Bladon
• Keywords: Organic chemistry
• Date of Award: 1962
• Depositing User: Enlighten Team
• Unique ID: glathesis:1962-73349
• 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/73349