Preparation of Phosphonic Acid Analogues of Proline and Proline Analogues and Their Biological Evaluation as δ1-Pyrroline-5-carboxylate Reductase Inhibitors
| Autor: | Giuseppe Forlani, Samuele Giberti, Thomas Kalina, Friedrich Hammerschmidt, Renzhe Qian, Jeannie Horak |
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| Rok vydání: | 2018 |
| Předmět: |
Phosphonic Acid Analogues of Proline
Proline Analogue Chemical Synthesis Biological Evaluation δ1‑Pyrroline-5- carboxylate Reductase Inhibitors Stereochemistry General Chemical Engineering δ1‑Pyrroline-5- carboxylate Reductase Inhibitors Reductase Alkylation 010402 general chemistry 01 natural sciences Article NO lcsh:Chemistry chemistry.chemical_compound Proline chemistry.chemical_classification Phosphonic Acid Analogues of Proline Ozonolysis 010405 organic chemistry Chemistry Chemical Synthesis Chloroacetates Proline Analogue General Chemistry 0104 chemical sciences Enzyme lcsh:QD1-999 Hydrazoic acid Biological Evaluation Derivative (chemistry) |
| Zdroj: | ACS Omega, Vol 3, Iss 4, Pp 4441-4452 (2018) ACS Omega |
| ISSN: | 2470-1343 |
| DOI: | 10.1021/acsomega.8b00354 |
| Popis: | Racemic 1-hydroxy-3-butenyl-, 3-chloro-1-hydroxypropyl-, and 3-bromo-1-hydroxypropylphosphonate and the corresponding (S)-enantiomers obtained by lipase-catalyzed resolution of the respective racemic chloroacetates were subjected to functional group manipulations. These comprised ozonolysis, Mitsunobu reactions with hydrazoic acid and N-hydroxyphthalimide, alkylation of hydrazine derivative, removal of phthaloyl group followed by intramolecular substitution, and global deprotection to deliver the racemates and (R)-enantiomers (ee 92–99% by chiral high-performance liquid chromatography) of pyrrolidin-2-yl-, oxazolidin-3-yl-, oxazolidin-5-yl-, pyrazolidin-3-yl-, and 1,2-oxazinan-3-ylphosphonic acids. These phosphonic acids were evaluated as analogues of proline and proline analogues for the ability to inhibit γ-glutamyl kinase, δ1-pyrroline-5-carboxylate synthetase, and δ1-pyrroline-5-carboxylate reductase. Only the latter enzyme was inhibited by two of them at concentrations exceeding 1 mM. |
| Databáze: | OpenAIRE |
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