888487-36-3

Upstream product

• 888487-35-2 1,5-anhydro-2-deoxy-3,4,6,7-tetra-O-tert-butyldimethylsilyl-L-galacto-hept-1-enitol 
• 97174-13-5 sodium dibenzyl phosphate 

Relevant academic research and scientific papers

Stereoselective glycal fluorophosphorylation: Synthesis of ADP-2-fluoroheptose, an inhibitor of the LPS Biosynthesis

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.

METHODS FOR PREPARING ENZYMATIC SUBSTRATE ANALOGS USEFUL AS INHIBITORS OF BACTERIAL HEPTOSYL-TRANSFERASES AND BIOLOGICAL APPLICATIONS OF THE INHIBITORS

The invention relates to a method for making osyl and hexoses derivatives of formula (1), especially 2-fluoro-2-deoxy derivatives, wherein R is a nucleoside such as adenosine, cytidine, guanosine, uridine and deoxy analogs such as 2-deoxy, X represents OH, halogen, particularly F, NH2, Y represents H, CH2OH, CH2NH2, CH2OPO3, CH2OSO3, Z represents O or S, and W represents O,NH, or CH2, said method comprising the steps of: a) stereoselective fluorophosphorylation of tetrapivaleate 8 to give β-gluco-type fluorophosphate, b) hydrogenation and deprotection to give a monophosphate, c) coupling said glycal with (R)P-morpholidate to give crude sugar nucleotide 1, or . alternatively, d)deacetylation then silylation of heptoglycal 7 to give tetrasilylated glycal, e)fluorophosphorylation of said glycal to give β-gluco type fluorophosphate, f) deprotection of the fluorophosphate and coupling radical R to give 1. Use of said derivatives as inhibitors of highly virulent proteins of pathogenic bacteria.