Alternative synthesis and antibacterial evaluation of 1,5-dideoxy-1,5-imino-l-rhamnitol

Abstract

A convenient synthesis is described of 5-azido-5-deoxy-2,3-O-isopropylidene-L-rhamnofuranose from L-rhamnose in seven steps and 17% overall yield. A key feature of the synthesis is the selective oxidation of the secondary alcohol in 2,3-O-isopropylidene-L-rhamnofuranose in the presence of the hemiacetal to give the corresponding ketone in good yield using the Parikh-Doering reagent. 5-Azido-5-deoxy-2,3-O-isopropylidene-L-rhamnofuranose is then converted by a literature protocol to 1,5-dideoxy-1,5-imino-L-rhamnitol, which was found to have no significant antimicrobial activity against Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Escherichia coli.

Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides

“…Thus, the galactofuranose derivatives 9 and 10 , , with the lyxo configuration at the branch point and the two flanking centers, both adopt the gg conformation of the side chain, which places the five-carbon chain from C2–C6 in an approximate zigzag conformation. The allofuranose derivative 11 with the ribo configuration of the conformation determining stereotriad adopts the predicted gt conformation of the side chain and has the sickle conformation of the C2–C6 carbon chain, as do the gulofuranose derivatives 12 and 13 with the xylo configuration of the key stereotriad. − Finally, the glucofuranose derivatives 14 and 15 and the manno- and rhamnofuranose derivatives 16 and 17 , respectively, all with the arabino configuration of the C4–C5–C6 stereotriad spanning the branch point, all adopt the tg conformation of the side chain and an approximate zigzag conformation of the C2–C6 carbon chain. ,− Seemingly, the combination of gauche, steric, and dipolar interactions that dominate the side chain conformations of the higher carbon pyranose derivatives and the conformations of the simple acyclic pentitols also operates in the hexofuranoses and does so even with a range of furanose ring conformations imposed by different protecting groups, as illustrated by the series 14−17, as illustrated by the series 14 – 17 .…”

Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S

“…29 The 6-membered polyhydroxylated piperidine iminosugars, represented by nojirimycin 1 30 and 1-deoxynojirimycin 2 31 are classical GH inhibitors. 32–34 These compounds mimic the ring size of the substrate and the charge that develops in a late transition state that is stabilized by the nucleophile in the active site. Polyhydroxylated pyrrolidines also show potent GH inhibitory activity.…”

Preference of Bacterial Rhamnosyltransferases for 6-Deoxysugars Reveals a Strategy To Deplete O-Antigens

“…As l -Rha-1-phosphate weakly bound to RfbF, we hypothesized that a reported 6-deoxy-iminosugar ( 2 ) , resembling l -Rha could block the donor site. We synthesized and then titrated 2 into E. coli WbbL reactions containing the native acceptor with the donor present around cellular concentrations . The resulting half maximal inhibitory concentration (IC 50 ) was ∼3 mM (Figure B).…”

“…Since O-Ag are virulence factors, we next aimed to evaluate the cellular consequences of WbbL inhibition. As l -Rha-1-phosphate weakly bound to RfbF, we hypothesized that a reported 6-deoxy-iminosugar ( 2 ) , resembling l -Rha could block the donor site. We synthesized and then titrated 2 into E. coli WbbL reactions containing the native acceptor with the donor present around cellular concentrations .…”

“…In contrast to well-studied bacterial glycosyltransferases, including the peptidoglycan precursor synthase MurG, , few RT inhibitors exist. , Since MurG uses the donor UDP-α - GlcNAc, methods to modulate MurG are not transferable to WbbL. Further, while the toxin colicin M depletes O-Ag by targeting carrier lipid modification, it also affects essential biosynthetic pathways .…”