XYLNAc和LYXNAc对映体的合成：2-N-乙酰氨基-1,2,4-三脱氧-1,4-亚氨基戊糖醇的8种立体异构体对β-N-乙酰己糖胺酶抑制作用的比较

Synthesis of the enantiomers of XYLNAc and LYXNAc: comparison of β-N-acetylhexosaminidase inhibition by the 8 stereoisomers of 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols.

作者信息

Crabtree Elizabeth V, Martínez R Fernando, Nakagawa Shinpei, Adachi Isao, Butters Terry D, Kato Atsushi, Fleet George W J, Glawar Andreas F G

机构信息

Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.

出版信息

Org Biomol Chem. 2014 Jun 21;12(23):3932-43. doi: 10.1039/c4ob00097h.

DOI:10.1039/c4ob00097h

PMID:24802185

Abstract

The enantiomers of XYLNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminoxylitol) are prepared from the enantiomers of glucuronolactone; the synthesis of the enantiomers of LYXNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminolyxitol) from an L-arabinono-δ-lactone and a D-ribono-δ-lactone is reported. A comparison is made of the inhibition of β-N-acetylhexosaminidases (HexNAcases) and α-N-acetylgalactosaminidase (α-GalNAcase) by 8 stereoisomeric 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols; their N-benzyl derivatives are better inhibitors than the parent compounds. Both XYLNAc and LABNAc are potent inhibitors against HexNAcases. None of the compounds show any inhibition of α-GalNAcase.

摘要

XYLNAc（2-N-乙酰氨基-1,2,4-三脱氧-1,4-亚氨基木糖醇）的对映体由葡糖醛酸内酯的对映体制备；据报道，LYXNAc（2-N-乙酰氨基-1,2,4-三脱氧-1,4-亚氨基来苏糖醇）的对映体由L-阿拉伯糖-δ-内酯和D-核糖-δ-内酯合成。对8种立体异构的2-N-乙酰氨基-1,2,4-三脱氧-1,4-亚氨基戊糖醇对β-N-乙酰己糖胺酶（己糖胺酶）和α-N-乙酰半乳糖胺酶（α-GalNAcase）的抑制作用进行了比较；它们的N-苄基衍生物比母体化合物是更好的抑制剂。XYLNAc和LABNAc都是己糖胺酶的有效抑制剂。这些化合物均未显示出对α-GalNAcase的任何抑制作用。