期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 16, 期 17, 页码 8273-8286出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.06.016
关键词
hydroxypipecolic acid; glycosidase inhibitor; azasugar; uronic type; both enantiomers
资金
- Grant-in-Aid for Scientific Research [18590012]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
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 beta-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 alpha- and beta-glucosidases. On the other hand, L-23 and L-29 were found to have potent inhibitory activity against beta-glucuronidase. In addition, it is interesting that some uronic-type azasugar derivatives showed moderate inhibitory activities against beta-N-acetylglucosaminidase. (C) 2008 Elsevier Ltd. All rights reserved.
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