Isofagomine lactams, synthesis and enzyme inhibition

被引：29

作者：

Lillelund, VH ^{[1
]}

Liu, HZ ^{[1
]}

Liang, XF ^{[1
]}

Sohoel, H ^{[1
]}

Bols, M ^{[1
]}

机构：

[1] Aarhus Univ, Dept Chem, DK-8000 Aarhus, Denmark

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2003年 / 1卷 / 02期

关键词：

D O I：

10.1039/b208784g

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The synthesis of isofagomine lactams (2-oxoisofagomines) corresponding to the biologically important hexoses is presented. The D-glucose/D-mannose analogue (3S,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (9) was synthesised in 9 steps from D-arabinose, the D-galactose analogue (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (10) was synthesised in I I steps from D-arabinose and the L-fucose analogue (3R,4R,5R)-3,4-dihydroxy-5-methylpiperidin-2-one (11) was synthesised in 12 steps from L-arabinose. The three lactams 9-11 were found to be glycosidase inhibitors with micro- to nanomolar inhibition constants. The lactam 10 showed slow onset inhibition of P-galactosidase from A. Oryzae. The rate constants for this process were determined to be k(on) = 2.55 x 10(4) M-1 s(-1) and k(off) = 1.7 x 10(-3) s(-1). The activation energies and standard thermodynamic functions were also determined.

引用

页码：282 / 287

页数：6

共 27 条

[21] All eight stereoisomeric D-glyconic-δ-lactams:: Synthesis, conformational analysis, and evaluation as glycosidase inhibitors [J].