Abstract:Optically pure L-( + )-C"-methyl-arginine and D-( -)-C"-methyl-arginine were synthesized. Experimental results indicated that DL-C"-methyl-arginine methyl ester could be resolved by trypsin, but workup posed a technical difficulty. Chemical resolution at the stage of DL-C"-methyl-ornithine, followed by selective guanidination using N,N'-di-Cbz-S-methylisothiourea and hydrogenolysis provided a effective and practical method for the synthesis of optically pure C"-methyl-arginine.
“…The synthesis of this compound was performed using the method reported for the guanidyl compounds . Triethylamine (27.2 mg, 269 μmol) and HgCl 2 (20.0 mg, 73.7 μmol) were added to a solution of 11 (20.0 mg, 22.4 μmol) and 19 (25.3 mg, 70.6 μmol) in dry dimethylformamide (DMF, 2.0 mL) at 0 °C. The resulting brown suspention was stirred at 0 °C for 1 h, and the mixture was diluted with CHCl 3 and filtered.…”
Cyclometalated iridium(III) complexes, because of their photophysical properties, have the potential for use as luminescent probes for cellular imaging. We previously reported on a pH-activatable iridium complex that contains three N,N-diethylamino groups, namely, fac-Ir(deatpy)3 5, which was synthesized via a regioselective aromatic substitution reaction at the 5'-position with tolylpyridine groups of fac-Ir(tpy)3 2. It was found that 5 shows a considerable enhancement in emission intensity in the pH range from neutral to slightly acidic (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3 cells, due to the protonation of the diethylamino groups. In addition, 5 functions as a pH-dependent singlet oxygen ((1)O2) generator and induces necrosis-like cell death. However, observing the green emission of 5 is often hampered by autofluorescence emanating from nearby tissues. To overcome this problem, we designed and synthesized a series of new pH-activatable Ir(III) complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand of Ir(mpiq)3 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red emission, namely, Ir(deampiq)3 13, Ir(gmpiq)3 14, Ir(imzmpiq)3 15, and Ir(imztfpiq)3 16. The emission intensity of these Ir complexes is enhanced substantially by protonation of their basic groups, and they induce the necrosis-like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission of Ir(mpiq-NO2)3 9 and Ir(tfpiq-NO2)3 10 is also reported.
“…The synthesis of this compound was performed using the method reported for the guanidyl compounds . Triethylamine (27.2 mg, 269 μmol) and HgCl 2 (20.0 mg, 73.7 μmol) were added to a solution of 11 (20.0 mg, 22.4 μmol) and 19 (25.3 mg, 70.6 μmol) in dry dimethylformamide (DMF, 2.0 mL) at 0 °C. The resulting brown suspention was stirred at 0 °C for 1 h, and the mixture was diluted with CHCl 3 and filtered.…”
Cyclometalated iridium(III) complexes, because of their photophysical properties, have the potential for use as luminescent probes for cellular imaging. We previously reported on a pH-activatable iridium complex that contains three N,N-diethylamino groups, namely, fac-Ir(deatpy)3 5, which was synthesized via a regioselective aromatic substitution reaction at the 5'-position with tolylpyridine groups of fac-Ir(tpy)3 2. It was found that 5 shows a considerable enhancement in emission intensity in the pH range from neutral to slightly acidic (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3 cells, due to the protonation of the diethylamino groups. In addition, 5 functions as a pH-dependent singlet oxygen ((1)O2) generator and induces necrosis-like cell death. However, observing the green emission of 5 is often hampered by autofluorescence emanating from nearby tissues. To overcome this problem, we designed and synthesized a series of new pH-activatable Ir(III) complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand of Ir(mpiq)3 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red emission, namely, Ir(deampiq)3 13, Ir(gmpiq)3 14, Ir(imzmpiq)3 15, and Ir(imztfpiq)3 16. The emission intensity of these Ir complexes is enhanced substantially by protonation of their basic groups, and they induce the necrosis-like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission of Ir(mpiq-NO2)3 9 and Ir(tfpiq-NO2)3 10 is also reported.
“…First the azido function was reduced without affecting the benzyloxy, and the benzyloxycarbonyl protective groups using Ph 3 P/H 2 O/THF 57 at 80 C through microwaves synthesis for 4 hours. The primary amine was then reacted in situ with N, N 0bis(benzyloxycarbonyl)-S-methylisothiourea 58 to give a mixture of diastereomers derivatives 13. The mixture of diastereomers was easily separated by simple flash chromatography to afford 13(a) and 13(b) in 41% and 37% yields, respectively.…”
Heat shock protein expression can be induced by heat shock making it possible to artificially modulate their levels noninvasively in vivo in a spatially and temporally controlled manner. Here, we report the use of the major heat shock protein 70 (HSP70) as an inducible target by using the small molecule deoxyspergualin (DSG) conjugated to the near-infrared fluorophore (Cy5.5). We demonstrate that heat induction in the form of localized hyperthermia of normal tissue in living mice results in sufficient HSP70 overexpression for detection with DSG-Cy5.5 conjugate. This effect is dependent on total energy delivered and reaches maximum fluorescence signal in 6 to 8 hours post heat induction and declines over a period of up to 24 hours. These results suggest that DSG-Cy5.5 agent accumulates in tissue with elevated HSP70 by heat.
“…For the introduction of the benzyl group, 12 and 16 were subjected to reductive amination reactions with benzaldehyde to furnish N δ -benzylated ornithines 29 and 30 , which could not be obtained in pure form. All didehydro-ornithines 12 , 16 , 29 and 30 were transformed into the respective arginine derivatives by guanidinylation with reagent 31 (Tian et al 1992) in the presence of silver(I) triflate. Thus, target structures 8e – h were obtained in yields of 42–71 % (over two or three steps from the respective δ-azido-didehydro α-amino acid).Fig.…”
The non-proteinogenic amino acids capreomycidine and epicapreomycidine are constituents of antibiotically active natural products, but the synthesis of these unusual cyclic guanidine derivatives is challenging. The biosynthesis of capreomycidine has therefore been employed as a guideline to develop a concise biomimetic synthesis of both epimeric amino acids. The resulting domino-guanidinylation-aza-Michael-addition reaction provides the most convenient access to these amino acids in racemic form. Attempts to dissect the domino reaction into two separate transformations for a stereocontrolled version of this synthetic approach have also been made. The synthesized didehydro-arginine derivatives with urethane-protected guanidine moieties did not undergo the aza-Michael-addition anymore. These results may have wider implications for the 1,4-addition of guanidines to α,β-unsaturated carbonyl compounds, particularly to didehydro amino acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-012-1309-8) contains supplementary material, which is available to authorized users.
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