Synthesis of fluorinated macrocyclic bis(indolyl)maleimides as potential 19F NMR probes for protein kinase C

Journal of Organic Chemistry

Volumn 64, Issue 12, 1999, Pages 4238-4246

  Goekjian, Peter G ^a   Wu, Guo Zhang ^a,d   Chen, Shi ^a   Zhou, Lanxin ^a   Jirousek, Michael R ^b,e   Gillig, James R ^b   Ballas, Lawrence M ^c,f   Dixon, Jeffrey T ^c  

^a MISSISSIPPI STATE UNIVERSITY   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c Sphinx Pharmaceutical Corporation   (United States)

^d Tyger Scientific Inc   (United States)

^e ABBOTT LABORATORIES   (United States)

^f Novalon Pharmaceutical Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIS(INDOLYL)MALEINMIDE; FLUORINE DERIVATIVE; MALEIMIDE DERIVATIVE; PROTEIN KINASE C; UNCLASSIFIED DRUG;

ARTICLE; DIAGNOSTIC VALUE; ENZYME ASSAY; ENZYME INHIBITION; NUCLEAR MAGNETIC RESONANCE; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 0033546089     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9808876     Document Type: Article

References (50)

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45. The diasteriomeric allylated aldol products 8a and 8b have similar vicinal coupling patterns, reflecting different dominant conformations 8a-A and 8b-A for the two series. The principal conformational feature is a gauche arrangement between the electronegative fluorine and oxygen atoms. The conformation around the C.3-C.4 bond is also consistent with the assigned behavior. Whereas the coupling between H.3 and H.4 in 8a shows an extended conformation with the two protons antiperiplanar, there is some distortion around the C.3-C.4 bond in 8b. This is consistent with a synpentane interaction between the C.4 oxygen and the ester functionality in conformation 8b-A. The coupling constants in the primary alcohols 9a,b and diols 10a,b reflect a similar conformational behavior, with the oxygens gauche to the fluorine in both series. equation presented
46. 50 of 5 nM against PKC-β (75% inhibition at 9.8 nM) and weak isoform selectivity.
47. It is important to let the LHMDS solution stand for 30 min until it reaches -78 °C. At higher temperatures, higher diasterioselectivities but much lower yields were obtained.
48. The aldol products were obtained as mixtures of the silylated and nonsilylated aldol products in highly variable ratios, from exclusively silylated to exclusively nonsilylated. We were unable to determine convincingly the experimental parameters responsible.
49. It is important to add the borohydride suspension within 1 min of preparing it. Allowing the suspension to stand for 15 min was found to decrease the yield.
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