Stereocontrolled glycosylation of sordaricin in the presence of ammonium salts

5 páginas, 2 figuras, 2 tablas.The glycosidation of sordaricin with deoxy sugars derivatives was studied under acid-promoted conditions and by anomeric O-alkylation with sordaricin triflate. In both methods, an important effect of added ammonium salts on the stereoselectivity of the glycosidation was observed.Peer reviewe

Stereoselective synthesis of the antifungal GM222712

4 páginas, 1 tabla, 4 esquemas.An efficient and convergent synthesis of the antifungal agent GM222712 is described. The approach involves the preparation of the modified sugar moiety followed by its stereoselective anomeric O-alkylation with sordaricin triflate 19.Peer reviewe

Synthesis of 5 -c-Chain-Extended Uridines by Reaction of 5 ’-Halonucleosidks With Malonic Acid Type Derivatives

Reaction of 3-N-benzyl-5′-deoxy-5′-haloderivatives of uridine with the carbanions derived from diethyl malonate, ethyl acetoacetate, ethyl cyanoacetate and malondinitrile afforded the corresponding highly functionalized 5′-C-chain-extended uridines

A Facile Regioselective 1-O-Deacylation of Peracylated Glycopyranoses

The regioselective deacylation of peracylated glycopyranoses 1-5 with ammonia in a polar aprotic solvent to the corresponding α-1-OH sugar derivatives 6-10 in total or high stereoselectivity is described

Synthesis of modified polyoxins by reaction of uridine-5′-aldehyde with trimethylsilyl cyanide and amino acids

The synthesis of six modified polyoxin derivatives containing an alkyl amino group replacing the peptide bond has been accomplished, in a one pot reaction, by condensation of 2′,3′-O-isopropylideneuridine-5′-aldehyde with trimethylsily cyanide, boron trifluoride etherate and an amino acid, in methanol. The reaction affords stereoselectively the diastereoisomer having at O-5′ the same absolute configuration as the natural polyoxins

Identification and Characterization of Hundreds of Potent and Selective Inhibitors of Trypanosoma brucei Growth from a Kinase-Targeted Library Screening Campaign

© 2014 Diaz et al. In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.Peer Reviewe

An improved two-resin method for the cleavage of tertiary amines from REM resin

4 pages, 1 figure, 1 table, 2 schemes.-- Printed version published Sep 17, 2001.The use of polymer-bound guanidine 6b or polymer-bound phosphazene 6c significantly improve the yield of the Hofmann elimination step in the preparation of tertiary amines using REM resin, providing products with superior purities and free from contamination with trialkylammonium salts.Peer reviewe

Synthesis and Antiviral Activity of 5’-O-Sulfamoyluridine Derivatives

A series of 5′-O-[[[[(alkyl)oxy]carbonyl] amino] sulfonyl] uridines have been synthesized by reaction of cyclohexanol, palmityl alcohol, 1,2-di-O-benzoylpropanetriol and 2,3,4,6-tetra-O-benzoyl-L-glucopyranose with chlorosulfonyl isocyanate and 2,3′-O-isopropylidene-uridine. Another series of 5′-O-(N-ethyl and N-isopropylsulfamoyl) uridines have been prepared by reaction of 2′,3′-O-isopropylidene and 2′,3′-di-O-acetyluridine with N-ethylsulfamoyl and N-isopropylsulfamoyl chlorides. All compounds were tested against HSV-2, VV, SV and ASFV viruses. 2′,3′-Di-O-acetyl-5′-O-(N-ethyl and N-isopropylsulfamoyl) uridine showed significant activities against HSV-2. 5′-O-[[[[(2,3,4,6-Tetra-O-benzoyl-β-L-glucopyranosyl)oxy]carbonyl]amino] sulfonyl]-2′,3′-O-isopropylideneuridine was very active against ASFV