Synthesis of both enantiomers of hydroxypipecolic acid derivatives equivalent to 5-azapyranuronic acids and evaluation of their inhibitory activities against glycosidases.

Abstract:

: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.

journal_name

Bioorg Med Chem

authors

Yoshimura Y,Ohara C,Imahori T,Saito Y,Kato A,Miyauchi S,Adachi I,Takahata H

doi

10.1016/j.bmc.2008.06.016

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

8273-86

issue

17

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(08)00564-6

journal_volume

16

pub_type

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