Příprava pokročilých prostaglandinových meziproduktů

Abstract

Prostaglandins are a group of lipid mediators with multiple pharmaceutical and veterinary applications. This thesis describes the efforts made in the development of a new strategy for the synthesis of Alfaprostol ů-chain. More specifically, several attempts were made in the preparation of the propargyl alcohol connection present in this molecule. Literature described two main methodologies for preparation of optically active propargylic alcohols, namely: asymmetric reduction of a propargylic ketone or the asymmetric alkynylation of a carbonyl group. Both mentioned methodologies were studied and applied to target molecule. Stille coupling has been successfully used to afford propargylic ketone susceptible of asymmetric reduction. The direct preparation of propargylic alcohol with adequate stereoselectivity using Corey lactone derivatives and 3- cyclohexylpropanal as starting materials was also deeply studied. Furthermore, it has also been used in the stereoselective studies made afterwards.