Synthesis of Nonnatural Nucleoside Diphosphate Sugars

Abstract

Recently, we reported an efficient chemical method for the synthesis of a variety of naturally occurring nucleoside diphosphate (NDP) sugars. This method, which is based on the cycloSal approach, can also be used, in principle, for the preparation of rare or even nonnatural NDP sugars. Herein, the syntheses of sulfoquinovose‐, glucose‐6‐sulfate‐, L‐galactose‐, and 2‐fluoroglycopyranoside‐containing NDP sugars are presented, as well as the synthesis of NDP sugars with non‐natural nucleosides. The reactions described gavestereoisomerically defined NDP sugars in high yields and short reaction times.

Fluorescently Labeled Substrates for Monitoring α1,3‐Fucosyltransferase IX Activity

“…Nevertheless, the yields of these coupling reactions were lower than those previously reported for the synthesis of natural and non‐natural NDP sugars 12b,c. 13 However, the reaction performed by the cyclo Sal method gave the best yield (39 %) of the product 6 reported so far 7. 21…”

“…In this approach, acceptor‐substituted cyclo Sal‐nucleotides serve as active phosphate ester building blocks, which can be treated with anomerically pure glycopyranosyl‐phosphates to yield the NDP‐sugar of interest. In addition to the previously reported efficient and reliable synthesis of a variety of naturally occurring NDP‐sugars, the successful application of the cyclo Sal technique for the synthesis of NDP‐sugars bearing nucleoside as well as sugar analogues has recently been reported 13. Furthermore, NDP‐sugars have been post‐synthetically modified 13.…”

“…In addition to the previously reported efficient and reliable synthesis of a variety of naturally occurring NDP‐sugars, the successful application of the cyclo Sal technique for the synthesis of NDP‐sugars bearing nucleoside as well as sugar analogues has recently been reported 13. Furthermore, NDP‐sugars have been post‐synthetically modified 13. Recently we showed that the method can also be used for the synthesis of NMP‐sugars, for example, N ‐acetylneuraminic acid (derivatives) 14…”

Synthesis of Pyranonucleoside‐6′‐triphosphates through the cycloSal‐Method

“…Mainly, the Ludwig method is used. [7][8][9][10][11][12][13] With this method the synthesis of nucleoside-5Ј-triphosphates (both natural and non-natural compounds) was accomplished in yields of up to 80 % starting from the cycloSal-compound (64 % starting from the nucleoside). This might explain the low yields that were obtained by this method.…”

Synthesis of cycloSal‐(Glycopyranosyl‐6)‐phosphates as Activated Sugar Phosphates

“…Phosphorylation and dephosphorylation of proteins by kinases/ phosphorylases has a regulatory effect; phosphorylated carbohydrates are used for regulation and are important intermediates in metabolism in nature. [6][7][8][9][10][11][12] Herein, we report the synthesis of cycloSal-masked glycopyranosyl phosphates, which opens a new synthetic route towards phosphorylated derivatives of carbohydrates, for example phosphate diester linked disaccharides. [3] Nucleoside diphosphate sugars are the substrates of glycosyltransferases, which catalyze the biosynthesis of oligo-and polysaccharides.…”