Synthesis of Glycosyl Phosphate Repeats and Their Analogues

Abstract

Glycosyl phosphate repeat structures are seen in bacterial- and protozoan-derived sugar chains and these sugar chains have ten or more glycosyl phosphate repeats in many cases. Chemical synthesis of glycosyl phosphate repeats and their analogues can contribute to reveal their biological functions and to develop novel glycoconjugate vaccines and drugs. However, there is no synthetic approach for such long repeats on demand and only few repeats could be synthesized by most conventional approaches. One of the major problems of this difficulty is derived from the instability of glycosyl phosphates and their synthetic intermediates especially under acidic conditions. We used fluorinated sugar analogues of glycosyl phosphates to overcome the instability and achieved a stepwise solid-phase synthesis of a compound containing five such repeating units using the phosphoramidite approach. In addition, we have developed a phosphorus atom modified analogues of glycosyl phosphate repeats by various strategies.