β-d-Ribofuranose as a Core with a Phosphodiester Moiety as the Enzyme Recognition Site for Codrug Development

Org Lett. 2024 Nov 14. doi: 10.1021/acs.orglett.4c03662. Online ahead of print.

Abstract

An ideal codrug design should be able to control drug release, offer selectivity during drug delivery, and break down into non-toxic fragments after biodegradation. Our design incorporates d-ribofuranose as the core, with carbamate and carbonate groups as linking joints, a phosphodiester moiety as an enzyme recognition site, and lenalidomide and paclitaxel as the constituent drugs. The codrug synthesis involves seven steps with a 33% overall yield. The target codrug increases its water solubility 685 times versus paclitaxel.