AbstractAbstract In this work, we describe the study of the behaviour of several 2,3-oxidopolyenes analogs of 2,3-oxidosqualene modified at the 18-19 double bond with the 2,3-oxidosqualene sterolcyclase of pig liver. This work has required the synthesis of these 2,3-oxidopolyenes, their reaction with the sterolcyclase of pig liver, the separation and identification of the reaction products and if necessary their purifications to establish their structures. We could specify the limits of acceptance and tolerance of the pig liver’s cyclase towards the modified 2,3-oxidopolyenes. Indeed, whereas the 2,3-oxidopolyene bearing two n-propyl chains on the C-19 carbon is inert to the enzyme (unchanged substrate recovered after prolonged time in the presence of the enzyme), its counterpart having an alkylidene cyclohexane moiety is mainly biotransformed in a tetracyclic lanosterol-type derivative. Thus, the incorporation of the C-19 carbon in a cyclic six-membered unit, decreases the steric demand and restores the capacity of the cyclase to transform this polyene. Moreover, we also showed for the first time that the biocyclisation of a 2,3-oxidopolyene in lanosterol-type derivative is not stereospecific. Indeed, the 2,3-oxidopolyene with the Z stereochemistry bearing on the C-19 carbon an ethyl and a n-propyl moiety is transformed into two tetracyclic derivatives (20S, 20R) in a 79/21 ratio. Their structures were established by a spectroscopic study and by comparison of their spectroscopic characteristics with those of authentic samples. The latter were synthesized according to a strategy implying the lanosterol side-chain degradation followed by the rebuilding of the adequate alkyl chains.
|Date of Award||18 Jan 2008|
|Supervisor||Alain Krief (Supervisor), Willy Dumont (Jury), Stéphane Vincent (Jury), P. DE CLERCQ (Jury) & Michel ROHMER (Jury)|
Contribution à l'étude de la biocyclisation d'oxydo-2,3 polyènes vis-à-vis de l'oxydo-2,3 squalène stérolcyclase du foie de porc
Sable, R. (Author). 18 Jan 2008
Student thesis: Doc types › Doctor of Sciences