Solid-Phase Stereocontrolled Synthesis of Oligomeric P-Modified Glycosyl Phosphate Derivatives Using the Oxazaphospholidine Method.

Abstract

Glycosyl phosphate repeating units can be found in the glycoconjugates of some bacteria and protozoa parasites. These structures and their P-modified analogs are attractive synthetic targets as antimicrobial, antiparasitic, and vaccine agents. However, P-modified glycosyl phosphates exist in different diastereomeric forms due to the chiral phosphorus atoms, whose configuration would highly affect their physiochemical and biochemical properties. In this study, a stereocontrolled method was developed for the synthesis of P-modified glycosyl phosphate repeating units derived from the lipophosphoglycan of Leishmania using the oxazaphospholidine approach. The solid-phase synthesis facilitated the elongation and purification of the glycosyl phosphate derivatives, while two P-modified glycosyl phosphates (boranophosphate and phosphorothioate) were successfully synthesized with up to three repeating units.