新颖高效的KDO及CMP-KDO酶抑制剂的合成方法

2-酮基-3-脱氧辛酸（KDO）是革兰氏阴性菌脂多糖的必要组成成分。CMP-KDO合成酶催化KDO形成5'-单磷酸胞苷KDO核糖（CMP-KDO）。抑制CMP-KDO合成酶会阻止CMP-KDO形成，导致脂多糖生物合成的停止，从而引起细菌死亡。2-deoxy-beta-KDO与8-amino-2,8-dideoxy-beta-KDO对CMP-KDO合成酶有很强的抑制活性，具有发展成为新型抗菌药的潜力。本课题旨在发展一种新颖高效的KDO合成方法，以甘露糖为原料，3步完成KDO的合成。在此基础上，快速完成2-deoxy-beta-KDO与8-amino-2,8-dideoxy-beta-KDO及其磷酸三酯与二茂铁类衍生物的合成，为进行抗菌活性的研究奠定基础。

2-Keto-3-deoxy-D-manno-octulosonic acid (KDO)is an essential component of the lipopolysaccharide of gram-negative bacteria. CMP-KDO synthetase catalyzes the convertion of KDO to the nucleotide sugar cytidine 5'-monophosphate KDO (CMP-KDO)and the inhibition of this enzyme will prevent the formation of CMP-KDO and thus lead to the stop of the biosynthesis of lipopolysaccharides. As a result, the growth of bacteria will be inhibited. 2-deoxy-beta-KDO and 8-amono-2,8-dideoxy-beta-KDO are potent inhibitors of CMP-KDO synthetase and potential for the development of novel antibacterial agents.This project aims to develop a 3-step,green and efficient route to the synthesis of KDO by using D-(+)-mannose as starting material. 2-Deoxy-beta-KDO and 8-amino-2,8-didexoy-beta-KDO and their phosphate triester or ferrocenyl derivatives will be prepared for antibacterial study.