Abstract
2-Deoxy-D-glucose (2-DG), a compound known to interfere with D-glucose and D-mannose metabolism, has been tested as a potential anticancer and antiviral agent. Preclinical and clinical studies focused on 2-DG have highlighted several limitations related to 2-DG drug-like properties, such as poor pharmacokinetic properties. To overcome this problem, we proposed design and synthesis of novel 2-DG prodrugs that subsequently could be tested using a variety of biochemical and molecular methods. We narrowed here our focus to esters of 2-DG as potential prodrugs based on the hypothesis that ubiquitous esterases will regenerate 2-DG, leading to increased circulation time of drug and adequate organ and tumor penetration. Testing this hypothesis in vitro and, especially, in vivo requires significant amounts of respective pure mono- and previously unknown di-acetylated water-soluble derivatives of 2-DG. Development of their efficient and practical method of synthesis was imperative. We describe novel facile and scalable syntheses of seven selectively acetylated water-soluble derivatives of 2-DG and present a detailed 1H and 13C NMR analysis of all final products. X-ray diffraction analysis has been performed for compound WP1122 that was selected for detailed preclinical and subsequent clinical evaluation as potential anticancer or antiviral agent.
Original language | English (US) |
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Article number | 108861 |
Journal | Carbohydrate Research |
Volume | 531 |
DOIs | |
State | Published - Sep 2023 |
Keywords
- 2-Deoxy-D-glucose
- 2-DG diacetates
- 2-DG monoacetates
- 2-DG prodrugs
- WP1122
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Organic Chemistry