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

• Published in: ACS omega Vol. 6; no. 30; pp. 20026 - 20041
• Main Authors: Sato, Kazuki, Hagio, Tomoya, Sano, Michi, Muramoto, Kazumasa, Yaoita, Aya, Noro, Mihoko, Hara, Rintaro Iwata, Wada, Takeshi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.08.2021
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.1c03058

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.