Background and Objective: Many recent studies have focused on the development
of methods to overcome the barriers faced by oral drug delivery. This
study describes the synthesis of three glycolipid-based drug delivery systems designed
to be associated with charged drugs to improve their oral bioavailability.
Methods: D-Glucose was used as a scaffold to construct charged glycolipids with
anionic and/or cationic properties. Three glycolipids with positive and negative functionalities
were designed, synthesized by various carbohydrate, lipid and Bocchemistry
methods. The products were purified by flash column chromatography
and characterized by ESI-MS and NMR.
Results: The first glycolipid was synthesized by complete lipidation of D-glucose
using lipoamino acids with positively charged amino groups. The negatively charged glycolipid was obtained
by coupling succinate bearing a free carboxylic group to lauroylated glucose. Combining both
strategies, the target compound, which can bear either positive or negative charges, was prepared
through the conjugation of succinate to the carbohydrate core followed by the addition of lipoamino
acids. Separation of the compounds from impurities (not fully lapidated derivatives) by flash column
chromatography proved to be challenging.
Conclusion: Ensuring the purity of all semi-products used in each reaction was paramount to prevent
complicated purification of the final compounds. Once the three glycolipids were carefully purified, protecting
groups were cleaved to give cationic and anionic properties. These glycolipids can undergo
complexation with charged drugs to improve their oral bioavailability. This system has the potential to
serve as a universal template for oral drug delivery.