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Title: Heterocyclic analogues of steroids containing a bridgehead nitrogen
Author: Bajwa, Joginder Singh
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1979
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The work contained in this thesis describes some of the many possible condensation reactions which take place between steroidal P-ketoaldehydes and aminoazoles; in all ten examples of P-dicarbonyl steroids were variously condensed with ten representative aminoazoles. Also reported are the reactions which are observed between steroidal abromo ketones and mercaptoazoles; nine examples of mercaptoazoles were used in conjunction with four steroids to illustrate these particular reactions. Throughout the above reactions, satisfactory mechanisms have been proposed to account for the observed products. It is shown that when 2-amino-1, 3, 4-thiadiazole is condensed with a 2-hydroxymethylene-3-oxo steroid, the product resulting from the cyclisation reaction, namely 2'thiocyanato-5a-androst-2-eno[3, 2-d]pyrimidine, contains a thiocyanato group formed by cleavage of the thiadiazole ring. A more typical reaction is observed during the condensation of 3-aminopyrazole with a 2-hydroxymethylene-3-oxo steroid. The reaction products are the linearly fused heterocycle, 5a-androstano[3, 2-f]pyrazolo[l, 5-a]pyrimidine and the iangularly fused isomer, 5a-androst-2-eno[2, 3-g]pyrazolo[l, 5-a]pyrimidine. The observance of two products from this type of condensation reaction appears to be quite general, however, the actual ratio of linearly fused to angularly fused isomer is found to be dependent upon the aminoazole as will as the steroid employed in the reaction. Condensations involving 2-hydroxymethylene-A-3-oxo steroids and 16-hydroxymethylene17-oxo steroids always result in a single reaction product. During the reaction between 3-amino-5-methylthio-1, 2, 4-triazole and 16-hydroxymethylene-17-oxo steroids, the intermediate P-ketoanils were isolated. These intermediates could be cyclised to the angularly fused triazolopyrimidines. P-Ketoanils, independently prepared from 2-hydroxymethylene-3-oxo steroids and 2-aminopyridine, have been shown to react with various aminoazoles to afford linearly fused heterocyclic products and these observations lend support to the reaction mechanism proposed for the general condensation reaction. The linearly fused condensation products were distinguished from the angularly fused isomers with the help of i.r., u.v., 1H n.m.r. and 13C n.m.r. spectroscopy. The reaction of various aminoazoles with 4,4- dimethoxybutan- 2- one, 2-hydroxymethylenecyclohexanone, 2-hydroxymethylenecyclopentanone and their corresponding Pketoanils obtained by the reaction of these P-ketoaldehydes with 2-aminopyridine, has also been investigated. The reaction of 2-mercaptoimidazoles and 3-mercapto-1,2,4-triazoles with 2abromo-3-oxo steroids gave the expected cyclised products 5a-androst-2-eno[2, 3-b]- i imidazo[Z,l-b]thiazoles and 5a-androst-2-eno[2,3-f]thiazolo[3,2-b]-s-triazoles respectively. However, the reaction of 2-mercaptoimidazole with Za-bromo-5n-cholestan-3-one in ethanol gave 5a-cholestano[2,3-b]-3p-ethoxy-Z',3'-dihydroimidazo[Z, 1-b]thiazole in addition to the expected cyclised product. The reaction of 3-mercapto-1, 2, 4-triazoles with 16a-bromo3-methoxyoestra-1,3,5(10)-trien-17-one gave only 3-methyloestra-1,3,5(10)-trieno[16,17-f] 16p-ethoxy-5', 6'-dihydrothiazolo[3, 2-b]-s-triazoles.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available