Derivatives of dihydrostreptomycin

Ferguson, Gillian K.J (1965) Derivatives of dihydrostreptomycin. MSc(R) thesis, University of Glasgow.

Abstract

The work already carried out on the chemical modification of naturally occurring antibiotics is reviewed. The reasons for carrying out these modifications are discussed. Antibiotics which have been modified chemically in some way include the penicillins, the cephalosporins, the tetracyclines, griseofulvin and the aminoglycoside antibiotics including streptomycin itself. The value of these modifications varies from compound to compound, the most successful derivatives which have been prepared, to date, being the derivatives of penicillin. Compounds have been prepared which are more active, which are active orally and which are active against penicillinase producing micro-organisms. Derivatives of other antibiotics have, generally, been less successful, although valuable information about structure-action relationships has been obtained. The derivatives of dihydrostreptoraycin which are considered in this thesis are glycosides of dihyirostreptobiosamine, a disaccharide composed of dihydrostreptose linked glycosidically with N-methyl -L glucosamine. The methods available for glycoside synthesis, the Koenigs-Knorr, the Helferich and the Fischer syntheses, are reviewed. A modification of the Fischer synthesis was used for the preparation of the bensyl glycoside of dihydrostreptobiosamine, using methyl dihydrostreptoblosaminlde as starting material. No clear mechanism for this reaction has so far been postulated and therefore a series of reactions was carried out in order to elucidate the mechanism. A and B-methyl dihydrosterptobiosaminides were prepared and separated in the form of their acetates which were then used to prepare benzyl penta-acetyldihydrostreptobiosaminide by transglycosidation. The fact that the a-anomer was formed in both cases indicates that, every time, it is the more stable isomer which is formed. Direct benzyl alcoholysis of dihydrostreptomycin also gave a-benzyl penta-acetyldihydrostreptobiosaminide, confirming that theory. Methanolsys of a-benzyl-acetyldihydrosteptobiosaminide gave only the a-anomer of methyl penta-acetyldihdrostrantobiosaminide. There is some indication that the furanose ring of dihydrostraptose facilitates the reaction, in analogy with the Fisoher glycoside synthesis.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: J B Stenlakes
• Keywords: Pharmacology
• Date of Award: 1965
• Depositing User: Enlighten Team
• Unique ID: glathesis:1965-73068
• 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/73068