Design and synthesis of 5-hydroxytryptamine analogues: The photochemistry of certain steroids

Coombes, G. E. A (1968) Design and synthesis of 5-hydroxytryptamine analogues: The photochemistry of certain steroids. PhD thesis, University of Glasgow.

Abstract

Design and Synthesis of 5-Hydroxytryptamine Analogues. - The primary processes of drug absorption, distribution, and metabolism are outlined, and their possible influence upon attempted correlations between chemical structure and pharmacological action emphasised. Theories concerning the mode of action of drugs and in particular the role of the receptor theory are reviewed. The general pharmacological and physiological properties of 5-hydroxytryptamine and related compounds are also discussed. Current views concerning the role of endogenous 5-hydroxytryptamine and the nature of the 5-hydroxytryptamine receptor are included. Certain previously reported compounds which may be regarded as "less flexible" analogues of 5-hydroxytryptamine and tryptamine are noted and attempts to prepare other similarly "rigid" analogues are described. Such compounds should prove useful in investigations aimed at determining the structural requirements of the 5-hydroxytryptamine receptor. Routes to 4- and 5-amino-1,3,4,5-tetrahydrobenz [c,d]indole and the corresponding 6-hydroxy derivatives, 3-amino-6-hydroxy-1,2,3,4-tetrahydrocarbazole, and 3-amino-7-hydroxy-1,2,3,4-tetrahydrocyclopent[b]indole are investigated, and successful syntheses are recorded. The Photochemistry of Certain Steroids.- The transformations by which light-sensitive compounds are modified under the influence of ultraviolet light are briefly outlined according to the chromophore responsible for the initial excitation; examples of such transformations are drawn, wherever possible, from previously reported light-induced reactions of pharmacologically and physiologically active molecules. The photochemistry of cortisone acetate, 11-ketoprogesterone and progesterone in ethanol is reported; the major products isolated from these reactions were the corresponding 5 beta-dihydrosteroids resulting from photochemically-induced reduction of the C (4,5) double bond. The photochemistry of certain 3-substituted 6-nitrocholest-5-enes is also reported; 3beta-chloro-, 3beta-acetoxy- and 3beta-trifluoroacetoxy-6-nitrocholest-5-enes in ethanol gave, as the major product, cholest-4-ene-3,6-dione-3-oxime. The 3beta-hydroxy derivative (6-nitrocholesterol), however, gave no oxime but 3beta-hydroxycholest-4-en-6-one and 6beta-nitrocholest-4-en-3beta-ol as major products. The mechanism of formation of these photo-products is discussed; the nature of the product would appear to depend upon the solvent employed for the irradiation, the C(3) substituent, and the wavelength of the radiation employed.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: S T Reid
• Keywords: Pharmacology
• Date of Award: 1968
• Depositing User: Enlighten Team
• Unique ID: glathesis:1968-74155
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Sep 2019 15:33
• Last Modified: 23 Sep 2019 15:33
• URI: https://theses.gla.ac.uk/id/eprint/74155