Synthesis, characterization and protein binding properties of supported dendrons (original) (raw)
Related papers
Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications
Organic & Biomolecular Chemistry, 2008
Instrumentation. 500 MHz 1 H and 125.7 MHz 13 C NMR spectra were recorded on a Bruker DRX-500 spectrometer and referenced to CDCl 3 (7.25 ppm) and DMSO-d 6 (2.50 ppm). 1 H-13 C gradient-selected HMQC and HMBC spectra were obtained by using 2048 (t 2 )×256 (t 1 ) complex point data sets, zero filled to 2048 (F 2 )×1024 (F 1 ) points. The spectral widths were 13 ppm and 200 ppm for 1 H and 13 C dimensions, respectively. HMBC spectra were measured with 50 ms delay for evolution of long-range couplings. (MA)LDI-TOF mass spectra were obtained using a Voyager Elite Biospectrometry Research Station (PerSeptive Biosystems, Vestec Mass Spectrometry Products) in a positive ion mode. EI-TOF HRMS and ESI-TOF HRMS spectra in positive ion mode were obtained using Micromass LCT reflection TOF mass spectrometer. Analytical thin-layer chromatography was performed on the Kieselgel 60 F 254 precoated aluminium plates (Merck), spots were visualised under UV light (254 nm). Column chromatography was performed on silica gel (Merck Kieselgel 60 0.040-0.063 mm). Reagents and solvents. Reagents obtained from commercial suppliers were used as received. 4-Hydroxy-4′-methoxybenzophenone (3), [1] Pd(PPh 3 ) 4 , tert-butyl 6-bromohexanoate, were prepared as described. Solvents were mainly HPLC grade and used without further purification unless otherwise noted. DCM was always used freshly distilled over CaH 2 . THF was distilled over powdered LiAlH 4 or over sodium benzophenone ketyl and stored over 4Å molecular sieves under nitrogen. DMF was freshly distilled under reduced pressure. OH O O O O O Cl(CH 2 ) 3 CO 2 Bu t MeONa / HMPA 75%
Chemistry - A European Journal, 2006
Results and Discussion Synthesis: The esters of the constitutional isomeric 3',4'-and 3',5'-dihydroxybiphenyl-4-carboxylic acids (4 a,b and 10) and of 3',4',5'-trihydroxybiphenyl-4-carboxylic acid (15) were selected as starting building blocks for the synthesis of the novel library of self-assembling dendrons. They are architecturally related to the benzyl ether and phenylpropyl ether dendrons reported previously by us. Scheme 1 outlines the synthesis of these building blocks. The synthesis of 3,4-(dimethoxy)phenyl-1-boronic acid 1 was accomplished according to a literature procedure. [17] The lithiation of 1-bromo-3,4-dimethoxybenzene with nBuLi at À78 8C was performed in THF under N 2 for 2.5 h. Subsequently, BA C H T U N G T R E N N U N G (OMe) 3 was added as the reaction mixture was allowed to warm to 22 8C over 14 h. Finally, the reaction mixture was treated with 15 % HCl at 22 8C to afford the boronic acid 1 in 64.9 % yield. 1-Bromo-3,4-dimethoxybenzene was synthesized by the electrophilic bromination of 1,2-dimethoxybenzene with n-bromosuccinimide in acetone. [18a] Methyl and ethyl 4-bromobenzoate (2 a,b) were synthesized from the corresponding commercially available acid by esterification with MeOH (EtOH) using H 2 SO 4 as catalyst at reflux for 18 h. The Suzuki coupling of 1 with 2 a,b, catalyzed by freshly prepared [PdA C H T U N G T R E N N U N G (PPh 3) 4 ], [18b] produced methyl and ethyl 3',4'-dimethoxybiphenyl-4-carboxylates (3 a,b) in 95 and 73 % yields, respectively. This Suzuki reaction can also be catalyzed by [NiCl 2 A C H T U N G T R E N N U N G (dppe)] (dppe = 1,2-bis(diphenylphosphino)ethane). [19] Compound 3 a was subsequently deprotected with BBr 3 [20] to give 4 a (78 %). Compound 3 b was treated with pyridinium hydrochloride [21] (PyHCl) to yield a mixture of 4 b and the corresponding acid was subsequently esterified by using a saturated solution of dry HCl in EtOH to give 4 b in 86 % overall yield. The 3',5'-dihydroxybiphenyl building block was prepared in a similar way. 4-Methylphenylboronic acid (6) [22] was cross-coupled with the commercially available 1-chloro-3,5dimethoxybenzene (5) by using an in situ prepared Pd complex with 2-(di-tert-butylphosphino)biphenyl as catalyst [23] to give the desired 3',5'-dimethoxy-4-methylbiphenyl 7 in 95 % yield. When this cross-coupling was catalyzed by
Synthesis and characterization of immobilized PAMAM dendrons
Chemical Communications, 2007
Dopamine b-hydroxylase (DBH) catalyzes the b-hydroxylation of dopamine to norepinephrine. The enzyme in chromaffin granules occurs in a soluble form and a form confined to the surrounding membrane. DBH was noncovalently immobilized in the hydrophobic interface of an immobilized artificial membrane (IAM) liquid chromatographic stationary phase and the resulting DBH-IAM stationary phase was enzymatically active and was shown to mimic the membranebound form of the enzyme. DBH was also covalently immobilized onto a silica-based support containing, glutaraldehyde-P (Glut-P). The resulting DBH-Glut-P interphase was also enzymatically active, reproducible and shown to display characteristics of the solubilized enzyme. The results demonstrate that the different immobilization methods utilized for the enzyme can be used to quantitatively and qualitatively determine the enzyme kinetic constants associated with enzyme / substrate and enzyme / inhibitor interactions for the two distinct forms of the enzyme. These new entities can be used in basic biochemical studies as well as in high throughput screening of substances for DBH substrate / inhibitor properties.
A new dendrimer series: synthesis, free radical scavenging and protein binding studies
RSC Advances, 2020
Tri-o-tolyl benzene-1,3,5-tricarboxylate (TOBT (T0)), tri-4-hydroxyphenyl benzene-1,3,5-tricarboxylate (THBT (T1)), and tri-3,5-dihydroxyphenyl benzene-1,3,5-tricarboxylate (TDBT (T2)), a series of 1st tier dendrimers with a common 1,3,5-benzenetricarbonyl trichloride/trimesoyl chloride (TMC) core, are reported. T0 does not have any replaceable H+ on its terminal phenyl group, acting as a branch. T1 has one phenolic –OH at the para position and T2 has two phenolic –OH groups at the 3 and 5 positions of each terminal phenyl group. During synthesis, these –OH groups at the terminal phenyl groups were protected through tert-butyldimethylsilyl chloride (TBDMSCl) assisted with t-BuOK in DCM, THF, indazole, 4-dimethylaminopyridine (DMAP), and tertiary-n-butyl ammonium fluoride (TBAF). MTBDMSP (mono-tertiary butyl dimethylsilane phloroglucinol), DTBDMSP (di-tertiary butyl dimethylsilane phloroglucinol), and TTBDMSP (tri-tertiary butyl dimethylsilane phloroglucinol) were obtained with >9...
Supporting Information Part I. Chemical Synthesis and Characterization General Procedures
All reagents were purchased from Sigma-Aldrich (St Louis, MO, USA) or Macrocyclics (Dallas, TX, USA) unless stated otherwise. Solvents were freshly distilled on appropriate driers and reactions run under an inert Argon atmosphere (CH 2 Cl 2 was distilled over P 2 O 5 , THF was distilled over sodium). All compounds apart from those containing Gd were fully characterized by 1 H (400 Hz) NMR, 13 C (400 Hz) (Bruker AMX-400 spectrometer) and the final products with Gd were characterized by mass spectrometry (EIMS and HRMS). Chemical shifts are expressed in δ ppm. All photophysical experiments were carried out using spectroscopic-grade solvents. Column chromatography was performed either over Silica Gel 60 (70-230 mesh) or neutral Alumina (Brockmann grade III, 50 mesh). UV-visible spectra were recorded on Varian Cary 50 Bio UV-visible spectrophotometer using CH 2 Cl 2 as solvent unless otherwise specified. Fluorescence spectra were recorded on a Varian Cary Eclipse fluorescence spectrophotometer with an excitation wavelength in the "Soret" band region between 410 and 425 nm.
Accelerated Growth of Dendrimers via Thiol-Ene and Esterification Reactions
Macromolecules, 2010
By taking advantage of the orthogonal nature of thiol-ene coupling and anhydride based esterification reactions, a facile and chemoselective strategy to dendritic macromolecules has been developed. The ability to interchange growth steps based on thiol-ene and anhydride chemistry allows the synthesis of fifth-generation dendrimers in only five steps and under benign reaction conditions. In addition, the presented coupling chemistries eliminate the traditional need for protection/deprotection steps and afford dendrimers in high yield and purity. The modularity of this strategy coupled with the latent reactivity of the alkene/hydroxyl chain ends was demonstrated by using different cores (alkene and hydroxyl functional), various AB 2 and CD 2 monomers and a range of chain end groups. As a result, three dendritic libraries were prepared which exhibited tunability of both the chemical functionality and physical properties including the fabrication of PEG hydrogels. *Corrsponding authors. MS with SCOUT-MTP Ion Source (Bruker Daltonics, Bremen) equipped with a nitrogen laser (337 nm), a gridless ion source, and reflector design. Size exclusion chromatography (SEC) analysis was performed on a TDA 301 Viscotek instrument equipped with two GMH HR -M columns with TSK-gel. Measurements were carried out at 35°C using THF (1.0 mL min -1 ) as mobile phase. A calibration method was created using narrow linear polystyrene standards. Corrections for the flow rate fluctuations were made using toluene as an internal standard.
Journal of Organic Chemistry, 1987
reported to give only p-anomers. The desired compound 3 was also the major product of glycosylation of the 6bromopurine 1, although the minor component was apparently the 9-CY isomer rather than the expected 7-0 isomer. In addition, the facile and direct isolation of the 9-P-deoxyribofuranosyl isomers precludes lengthy chromatographic separation of glycosylation products. In the final step, the protected 2,6-dihalo nucleosides are converted nearly quantitatively to the target 2-halo-2'deoxyadenosines. This chemical method appears to be adaptable to large-scale syntheses, as demonstrated by the 50-fold greater scale of the glycosylation of 2,6-dibromopurine as compared with the enzymatic glycosylation of 2-br0moadenine.~