1101183-46-3Relevant academic research and scientific papers
Stereoselective glycal fluorophosphorylation: Synthesis of ADP-2-fluoroheptose, an inhibitor of the LPS Biosynthesis
Dohi, Hirofumi,Perion, Regis,Durka, Maxime,Bosco, Michael,Roue, Yvain,Moreau, Francois,Grizot, Sylvestre,Ducruix, Arnaud,Escaich, Sonia,Vincent, Stephane P.
experimental part, p. 9530 - 9539 (2009/09/30)
Heptosides are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP-L-glycero-β-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 stereoselective installation of both the fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor-mediated (selectfluor= 1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2] octane bis(triflate)) electrophilic addition/nucleophilic substitution involving a heptosylglycal. 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 β-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.
