Novel eco-friendly solution for the regioselective acetylation of per-O-TMS carbohydrates

Selective Acetylation of Non-anomeric Groups of per-O-Trimethylsilylated Sugars

“…To this effect, the yield of 25 (Table , entry 2) is particularly the lowest presumably due to the poor reactivity of the 4- O -TMS group of 20 . On the other hand, previous works utilizing different acetylation conditions revealed that the anomeric O -TMS group of both per- O -silylated monosaccharides and disaccharides was among the first groups to undergo the silyl exchange reaction. ,, Meanwhile, the attainment of per-acetylated 1- O -TMS lactose 28 (Table , entry 5) shows that our established acetylation protocol can effectively differentiate the slight reactivity variations in multi-hydroxylated sugars.…”

“…On the other hand, previous works utilizing different acetylation conditions revealed that the anomeric O-TMS group of both per-O-silylated monosaccharides and disaccharides was among the first groups to undergo the silyl exchange reaction. 12,13,16 Meanwhile, the attainment of per-acetylated 1-O-TMS lactose 28 (Table 3, entry 5) shows that our established acetylation protocol can effectively differentiate the slight reactivity variations in multi-hydroxylated sugars. The exploitation of the marginal nucleophilicity differences in the hydroxyl groups of glycopyranose sugars has been a common strategy to separately modify each group using a variety of reaction conditions; it is well-recognized that the electron density around a nucleophile is influenced by its inductive and steric environments.…”

“…Thus, we first tested our protocol in a per-O-TMS-protected derivative of D-glucose (14) and was then extended to other analogous sugar substrates. Accordingly, we prepared the respective per-O-TMS-protected sugars from commercially available 14, D-galactose (15), D-mannose (16), L-fucose (17), and the disaccharide lactose (18) based on a procedure from the literature. 46 Then, the resulting per-O-TMS-protected products 19−23 were subjected to our developed acetylation condition.…”

“…The majority of per-acetylation reactions are carried out using excess acetic anhydride (Ac 2 O) as an acetylating agent in the presence of pyridine or its derivatives like 4-(dimethylamino)­pyridine , as catalysts, though plenty of other protocols are also available . In order to address the issue of regioselectivity in acetylations, a number of attempts have been made over the past several years involving reactions by both chemical − and enzymatic , methods. However, these reactions utilize building blocks where the anomeric hydroxyl functionality is either already protected or free but is one of the target groups in the acetylation process.…”