SYNTHESIS OF AN ANALOG OF THE NUCLEOSIDE MOIETY OF THE POLYOXINS

Article abstract of DOI:10.1016/S0008-6215(00)85132-0

Addition of methyl nitroacetate to 1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose in the presence of ammonium acetate in anhydrous N,N-dimethylformamide afforded 1,2:5,6-di-O-isopropylidene-3-C-(R,S)nitro(methoxycarbonyl)methyl-α-D-allofuranose (2).Reduction of the nitro acetate 3 over palladium-on-charcoal gave the oxime 4, whereas reduction of 3 over Raney nickel afforded methyl L- (and D)-2-(3-O-acetyl-1,2:5,6-di-O-isopropylidene-α-D-allofuranos-3-yl)-glycinates (5 and 6), in 67 and 8percent yields, respectively.Saponification of 5 and 6 afforded the glycos-3-yl-α-amino acids 11 and 12.Conversion of the allofuranos-3-yl adduct 2 into the glucofuranos-3-yl reduction-products 13 and 14 was achived by treatment of 2 with methanol and acetic anhydride in the presence of palladium-on-charcoal.The N-trifluoracetyl derivative (10) of 5, underwent selective hydrolysis by 66percent acetic acid to afford a diol that was acetylated to afford the allo tri-acetate 15.The 5,6-glycol was selectively degraded by standard reactions to yield methyl N-acetyl-L-2-(5-O-acetyl-1,2-O-isopropylidene-α-D-ribofuranos-3-yl)glycinate (19).Application of the triflate-alkylation synthesis of nucleosides to the allo trifluoroacetyl amino acid 15 and silylated thymine yielded 1-<2,3,5,6-tetra-O-acetyl-<3-C-(methyl N-trifluoroacetyl-L-2-glycinate)>-β-D-allofuranosyl>thymine (23) in 93percent yield.Deprotection of 23 to yield the nucleoside amino acid 25 was not successful.