title: The dioxanone approach to (2S,3R)-2-C-methylerythritol 4-phosphate and 2,4-cyclodiphosphate, and various MEP analogues.
abstract: Efficient syntheses of the non-mevalonate pathway intermediates 2-C-methylerythritol 4-phosphate (MEP) and 2-C-methylerythritol 2,4-cyclodiphosphate (ME-2,4-cycloPP), as well as the parent tetrol 2-C-methylerythritol, in enantiopure form from (2S,4R)-cis-2-phenyl-4-tert-butyldimethylsilyloxy-1,3-dioxan-5-one are reported. The 2S configuration of the C-methyl group was installed by highly axial-face selective addition of CH3MgBr (20:1) to the chiral dioxanone carbonyl group. Primary selective mono-phosphorylation and 2,4-bis-phosphorylation, followed by desilation and hydrogenolysis to the free mono- and diphosphates, and, in the latter case, cyclization to form the eight-membered phosphoryl anhydride, afforded MEP and ME-2,4-cycloPP in good yields. The C2 epimeric analogues, 2-C-methylthreitol and its 4-phosphate, were accessed by LiAlH4 reduction of the cis,cis epoxide of (2S,4R)-4-tert-butyldimethylsilyloxymethyl-5-methylene-2-phenyl-1,3-dioxane, primary-selective phosphorylation, and cleavage of the silyl, benzylidene, and benzyl protecting groups. Regioselective cleavage of the acetal ring of 1,3-benzylidene 2-C-methylerythritol silyl ether by ozonolysis afforded a 1,2,3-triol 3-monobenzoate intermediate that was converted to the novel amino sugar, 1-amino-1-deoxy-2-C-methylerythritol.
authors.affiliation: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Chandraiah
authors.initials: C
authors.lastname: Lagisetti
authors.forename: Marek
authors.initials: M
authors.lastname: Urbansky
authors.forename: Robert M
authors.initials: RM
authors.lastname: Coates
mesh_terms: D004146:Dioxanes / Q000737:chemistry*; D004896:Erythritol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D013403:Sugar Phosphates / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C114232:2-C-methylerythritol 4-phosphate; D004146:Dioxanes; D013403:Sugar Phosphates; C443879:methyl-D-erythritol 2,4-cyclodiphosphate; C059814:4-dioxanone; D004896:Erythritol