Stereoselective Glycal Fluorophosphorylation: Synthesis of ADP-2-fluoroheptose, an Inhibitor of the LPS Biosynthesis
Stereoselective Glycal Fluorophosphorylation: Synthesis of ADP-2-fluoroheptose, an Inhibitor of the LPS Biosynthesis
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DOI：
10.1002/chem.200801279
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Vincent, Stephane P.
中科院分区：
文献类型：
--
作者：
Dohi, Hirofumi;Perion, Regis;Vincent, Stephane P.
庚糖苷存在于重要的细菌糖脂中，例如脂多糖（LPS）。其生物合成旨在开发新型抗菌剂。这项工作描述了 ADP-L-甘油-β-D-甘露-吡喃庚糖的氟化类似物的合成，它是庚基转移酶 WaaC 的供体底物，催化该碳水化合物掺入 LPS。综合而言，制备 ADP-2F-庚糖的关键步骤是通过 selectflu 介导的 (selectflor= 1-clilol-omettivi-4-氟重氮基-双环[2.2.2]辛烷双(三氟甲磺酸酯)) 电泳加成/亲核取代，同时立体选择性安装 C-2 处的氟原子和 C-1 处的磷酰基。庚基化。因此，我们在本文中详细介绍了 1) 关键中间体庚糖基糖的立体选择性制备，2) 开发了一种新的氟磷酸化程序，可实现与“全赤道”糖基的出色 β-葡萄糖立体选择性，3) 目标 ADP-2F-庚糖的合成，以及 4) 对最终分子的氟原子与晶体结构中的蛋白质之间观察到的接触的一些评论庚糖基转移酶 WaaC。
Heptosides are found in important bacterial glycolipids such as lipopolysaccliaride (LPS). the biosynthesis of which is targeted for the develoopment of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP-L-glycero-beta-D-manno-heptopyranose, the donor substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of this carbohydrate into LPS. Synthetically, the key step for the preparation of ADP-2F-heptose is the Simultaneous and stercoselective installation of both the fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor-mediated (selectfluor= 1-clilol-omettivi-4-fluorodiazonia-bicy[2.2.2]octane bis(triflate)) electrophific addition/nucleophilic substitution involving a heptosylplycal. Therefore, we detail in this article 1) the stereoselective preparation of the key intermediates heptosylglycals, 2) the development of a new fluorophosphorylation procedure allowing an excellent beta-gluco stereoselectivity with "all-equatorial" glycals, 3) the synthesis of the target ADP-2F-heptose, and 4) some comments on the contacts observed between the fluorine atom of the final molecule and the protein in the crystallographic structure of heptosyltransferase WaaC.