3-脱氧-D-甘露糖辛酮酸（KDO）类似物的合成作为CMP-KDO合成酶的潜在抑制剂

Synthesis of analogues of 3-deoxy-D-manno-octulosonic acid (KDO) as potential inhibitors of CMP-KDO synthetase.

作者信息

Luthman K, Claesson A, Jansson A M, Pring B G

机构信息

Department of Organic Pharmaceutical Chemistry, University of Uppsala, Sweden.

出版信息

Carbohydr Res. 1987 Sep 1;166(2):233-51. doi: 10.1016/0008-6215(87)80060-5.

DOI:10.1016/0008-6215(87)80060-5

PMID:2824049

Abstract

A series of derivatives of the 2-deoxy analogue of beta-KDO (2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid; ammonium salt, 2) has been synthesised as potential inhibitors of CMP-KDO synthetase, starting from methyl 2,6-anhydro-3-deoxy-4,5:7,8-di-O-isopropylidene-D-glycero-D-talo- octonate and replacing the CO2Me group attached to C-2 variously by CONH2, CONHOH, CH2OH, CH2PO(OH)(O-NH4+), COCH2PO(OH)(O-H3N+pheny), CH2CO2-NH4+, CON-HCH2CO2-NH4+, CONHBn, CONHHexyl, CO2Bn, and CO2Hexyl. Of these derivatives, the hydroxamic acid (CONHOH) was the best inhibitor of CMP-KDO synthetase, but was less potent than 2.

摘要

已合成了一系列β-KDO（2,6-脱水-3-脱氧-D-甘油-D-塔罗-辛酸铵盐，2）的2-脱氧类似物衍生物，作为CMP-KDO合成酶的潜在抑制剂，起始原料为2,6-脱水-3-脱氧-4,5:7,8-二-O-异丙叉基-D-甘油-D-塔罗-辛酸甲酯，并将连接在C-2上的CO2Me基团分别用CONH2、CONHOH、CH2OH、CH2PO(OH)(O-NH4+)、COCH2PO(OH)(O-H3N+苯基)、CH2CO2-NH4+、CON-HCH2CO2-NH4+、CONHBn、CONHHexyl、CO2Bn和CO2Hexyl取代。在这些衍生物中，异羟肟酸（CONHOH）是CMP-KDO合成酶的最佳抑制剂，但效力低于2。