Process for synthesis of complex 2-deoxy-2-iodo pyranosides of high purity, particularly suitable for manufacturing pharmaceutically pure annamycin

摘要

The method according to the invention comprises using as glycosyl donors high purity 2-deoxy-2-iodo derivatives of sugars of a defined configuration of C-2 carbon with O-alkyl, S-alkyl, O-aryl, S-aryl, O-heteroaryl, S-heteroaryl, O-acyl, O-silyl, O-N-imido, O-P-(phosphino, phosphono, thiophosphono, selenophosphono) groups at the anomeric position, and subjecting them to a condensation reaction with a compound containing a hydroxyl group or a protected hydroxyl group in the presence of electrophilic reagents, followed by deprotection and isolation of a pharmaceutically pure product. The objective of the present invention is to provide a method for preparing complex glycosides by coupling cyclic multifunctional compounds containing hydroxyl functional groups (glycosyl acceptors, including aglycones of natural origin which are known as constituents of active pharmaceutical ingredients) with diastereoisomerically pure 2-deoxy-2-halopyranosyl derivatives containing anomeric substituent capable of exchange under glycosidating conditions, for example by virtue of activation with electrophilic agents. This method substantially simplifies the synthesis of Annamycin.;The present invention relies on a regio- and stereoselective reaction of cohalogenating 1,2-unsaturated sugars in the presence of hydroxyl group containing compounds, such as: water, alcohols, phenols, carboxylic acids, silanols, phosphinic acids, phosphoric acids, thiophosphoric acids, selenophosphoric acids, followed by separation of the product with proper C-2 carbon configuration required for the synthesis. As the separation of stereoisomers is carried out at the stage of obtaining a relatively inexpensive intermediate in the form of glycosyl donor, the method of the invention substantially reduces the cost of Annamycin manufacture. Other advantages of the synthesis process of the invention consist in the reduction of the number of stages of the antibiotic manufacture process and in yield increase of the final product.