Synthesis of both enantiomers of hydroxypipecolic acid derivatives equivalent to 5-azapyranuronic acids and evaluation of their inhibitory activities against glycosidases
| Autor: | Chiaki Ohara, Isao Adachi, Atsushi Kato, Tatsushi Imahori, Hiroki Takahata, Saori Miyauchi, Yukako Saito, Yuichi Yoshimura |
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| Rok vydání: | 2008 |
| Předmět: |
Time Factors
Glycoside Hydrolases Stereochemistry Clinical Biochemistry Pharmaceutical Science Uronic acid Biochemistry Chemical synthesis Kinetic resolution Structure-Activity Relationship chemistry.chemical_compound Column chromatography Aldol reaction Drug Discovery Animals Humans Organic chemistry Enzyme Inhibitors Molecular Biology Aza Compounds Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Acrolein Temperature Diastereomer Stereoisomerism Enzyme Activation Uronic Acids Pipecolic Acids Molecular Medicine Cattle Enantiomer Chickens |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:8273-8286 |
| ISSN: | 0968-0896 |
| Popis: | We have synthesized 3-hydroxy- and 3,4,5-trihydroxypipecolic acid derivatives corresponding to 5-aza derivatives of uronic acids and evaluated their inhibitory activities against various glycosidases including β-glucuronidase. Compounds 4 and 5 were chosen as common intermediates for the synthesis of 3,4,5-trihydroxypipecolic acids and 3-hydroxypipecolic acids as well as for 3-hydroxybaikiain, a unique natural product isolated from a toxic mushroom. Cross aldol reaction of N-Boc-allylglycine derivative with acrolein followed by the ring-closing metathesis gave 4 and 5 as a mixture of diastereomers which could be separated by silica gel column chromatography. By employing lipase-catalyzed kinetic resolution, the synthesis of both l - and d -isomers of 3,4,5-trihydroxy- and 3-hydroxypipecolic acids was achieved. None of the compounds tested showed inhibitory activity against α- and β-glucosidases. On the other hand, l -23 and l -29 were found to have potent inhibitory activity against β-glucuronidase. In addition, it is interesting that some uronic-type azasugar derivatives showed moderate inhibitory activities against β-N-acetylglucosaminidase. |
| Databáze: | OpenAIRE |
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