A concise strategy for polymer-supported regio-oriented introduction of various building blocks onto glucopyranoside scaffold

A new strategy was devised to stereo-specifically introduce various building blocks, mainly heterocycles such as pyrimidines and triazines onto a multi-hydroxy molecule. A glucopyranoside was chosen as a target scaffold. Two polymer-based protective reagents were jointly integrated in the implementation of the strategy. It was found that in the α-D-glucopyranoside, which has four free hydroxyl groups within the same molecule, its 4, 6-di-OH could be simultaneously protected by polystyryl boronic acid, which left the 2, 3-di-OH free for substitution. Due to the steric effects within the molecule, the 2-OH is much more liabile to electrophilic substitution. Thus the first and the second building blocks could be introduced regioselectively onto the 2-OH and the 3-OH positions. After a facile deprotection, the 4, 6-di-OH were left free and by application of a second protecting reagent–-polystyryltritylchloride onto 6-OH, a third building block was introduced onto the 4-OH position. After further deprotection, the fourth building block was later introduced onto the 6-OH position. The new strategy was successfully applied in the combinatorial synthesis by application of the split-mix technique. The respective eleven small libraries were obtained and confirmed by HPLC-MS and NMR. Some preliminary results on chemical structure/herbicidal activity relationship were discussed.