Synthesis of analogues of 3-deoxy-D-manno-octulosonic acid (KDO) as potential inhibitors of CMP-KDO synthetase.
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.
Luthman
K
K
Department of Organic Pharmaceutical Chemistry, University of Uppsala, Sweden.
Claesson
A
A
Jansson
A M
AM
Pring
B G
BG
D007202:Indicators and Reagents; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013400:Sugar Acids / Q000138:chemical synthesis* / Q000494:pharmacology*
D007202:Indicators and Reagents; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate; D009713:Nucleotidyltransferases; C028984:3-deoxy-manno-octulosonate cytidyltransferase