129870-02-6Relevant articles and documents
Synthesis of fluorinated macrocyclic bis(indolyl)maleimides as potential 19F NMR probes for protein kinase C
Goekjian, Peter G.,Wu, Guo-Zhang,Chen, Shi,Zhou, Lanxin,Jirousek, Michael R.,Gillig, James R.,Ballas, Lawrence M.,Dixon, Jeffrey T.
, p. 4238 - 4246 (1999)
Six macrocyclic bis(indolyl)maleimides 1-6 bearing a fluorine label on the aliphatic portion of the macrocycle have been prepared as potential fluorine NMR probes for the catalytic domain of protein kinase C. The macrocyclic bis(indolyl)maleimides such as LY333531 are reversible, ATP competitive, and isoform-selective inhibitors of protein kinase C and may thus serve to probe for subtle differences between protein kinase catalytic domains. The key stereochemical elements were put in place by a Welch aldol condensation between ethyl fluoroacetate and (R)-cyclohexylidene glyceraldehyde, which was followed by allylation of the secondary alcohol, elaboration of the alkene and ester to alcohols, and mesylation. The macrocycle was formed by slow addition of a mixture of the fluorine-labeled aliphatic dimesylate and N-methyl 2,3-bis[1H-indol-3-yl]maleimide to a suspension of cesium carbonate. Adjusting the functionality led to the six fluorine-labeled macrocyclic bis(indolyl)maleimides. These compounds retain the high potency of the parent compounds, with IC50 values below 5 nM for the 14-membered ring compounds 1-3 and 13-90 nM for the 15-membered ring compounds 5-6. Vicinal proton-fluorine coupling constants provide an experimental parameter for determining the local macrocycle conformation.
Preparation of 2,3-Epoxyaldonolactones and their Conversion into 2-Fluoro-2-deoxy-aldonolactones and -sugars
Bols, Mikael,Lundt, Inge
, p. 252 - 256 (2007/10/02)
Treatment of the 2-bromo-2-deoxylactones 1, 2 and 8 with potassium fluoride in acetonitrile or acetone gives the corresponding 2,3-epoxylactones 4,5 and 10, respectively.The γ-lactones 5 and 10 were in equilibrium with the corresponding δ-lactones 7 and 12.The 2,5-dibromo-2,5-dideoxypentonolactones 3 and 9 gave the 2,3-epoxylactones 6 and 11, respectively, when treated with potassium carbonate in acetone.By treatment of the 2,3-epoxylactones with Et3N*3HF at 70 deg C for 3-13 days the 2-fluoro-2-deoxylactones 13, 15 and 18 were obtained in 57-69 percent yield; 15 and 18 were converted into 2-fluoro-2-deoxy-D-xylose (17) and -D-arabinose (19), respectively.Hydrolysis of 13 gave crystalline 2-fluoro-2-deoxy-L-threonic acid.
