Journal article
An improved synthesis of alkyl AMP esters
Tetrahedron letters, Vol.151, 155329
11/13/2024
DOI: 10.1016/j.tetlet.2024.155329
Abstract
•Alkyl AMP phosphate esters are highly valuable compounds.•Previous synthetic routes to AMP esters have been operationally difficult.•AMP esters can be synthesized using 5′-adenylic acid, EDC·HCl, and an alcohol.•Alkyl AMP esters can be purified by normal phase silica gel chromatography.
Enzymes belonging to the Acyl-CoA/NRPS/Luciferase (ANL) superfamily of enzymes, are significant targets in drug development. One member of this superfamily is Acetyl-CoA Synthetase (ACS). This enzyme is an emerging target for the treatment of various infectious diseases and cancer. Alkyl AMP esters have emerged as potent inhibitors of ACS. Previous methods for synthesizing these esters often involved water-based reactions or necessitate purification through reverse phase prep-HPLC or ion-exchange chromatography. To address these challenges, we developed a new approach utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) to couple 5′-adenylic acid to the corresponding alcohol, utilizing triethylamine as the base. This method yielded primary, secondary, unsaturated, and cyclic alcohols in excellent yields. Importantly, we optimized the reaction conditions to achieve excellent yield and purity without the need for reverse phase prep-HPLC or ion exchange chromatography. Instead, purification was achieved through silica gel chromatography using Biotage ® Sfar spherical silica gel.
Details
- Title: Subtitle
- An improved synthesis of alkyl AMP esters
- Creators
- Taiwo E. Esan - Northern Illinois UniversityCharles L. Lail - Northern Illinois UniversityDrashti G. Daraji - Northern Illinois UniversityDamian J. Krysan - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesTimothy J. Hagen - Northern Illinois University
- Resource Type
- Journal article
- Publication Details
- Tetrahedron letters, Vol.151, 155329
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.tetlet.2024.155329
- ISSN
- 0040-4039
- eISSN
- 1873-3581
- Grant note
- NIH: 5R01AI161973 NSF under the MRI: CHE-2117776 Northern Illinois University: RRID:SCR_024586 National Science Foundation: 1726931
This work was supported by NIH grant 5R01AI161973. Purchase of the NMR spectrometer used to obtain results included in this publication was supported by the NSF under the MRI award CHE-2117776. This work was supported by Northern Illinois University's Molecular Analysis Core (RRID:SCR_024586) which was established with support from Shimadzu Scientific Instruments, supported by the National Science Foundation under Grant No. 1726931. The authors would also like to thank Northern Illinois University for providing the facilities for this research.
- Language
- English
- Date published
- 11/13/2024
- Academic Unit
- Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984738439402771
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