Structure of N-Boc-2-pyrroleboronic acid
CAS No.: 135884-31-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Near infrared emitting semiconductor polymer dots for bioimaging and sensing
Riahin, Connor ; Mendis, Kushani ; Busick, Brandon ; Ptaszek, Marcin ; Yang, Mengran ; Stacey, Gary , et al.
Abstract: Semiconducting polymer dots (Pdots) are rapidly becoming one of the most studied nanoparticles in fluorescence bioimaging and sensing. Their small size, high brightness, and resistance to photobleaching make them one of the most attractive fluorophores for fluorescence imaging and sensing applications. This paper highlights our recent advances in fluorescence bioimaging and sensing with nanoscale luminescent Pdots, specifically the use of organic dyes as dopant molecules to modify the optical properties of Pdots to enable deep red and near infrared fluorescence bioimaging applications and to impart sensitivity of dye doped Pdots towards selected analytes. Building on our earlier work, we report the formation of secondary antibody-conjugated Pdots and provide Cryo-TEM evidence for their formation. We demonstrate the selective targeting of the antibodyconjugated Pdots to FLAG-tagged FLS2 membrane receptors in genetically engineered plant leaf cells. We also report the formation of a new class of luminescent Pdots with emission wavelengths of around 1000 nm. Finally, we demonstrate the formation and utility of oxygen sensing Pdots in aqueous media.
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Keywords: near infrared emission ; polymer dots ; plant cell imaging ; sensing
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CAS No. : | 135884-31-0 |
Formula : | C9H14BNO4 |
M.W : | 211.02 |
SMILES Code : | O=C(N1C(B(O)O)=CC=C1)OC(C)(C)C |
MDL No. : | MFCD01318939 |
InChI Key : | ZWGMJLNXIVRFRJ-UHFFFAOYSA-N |
Pubchem ID : | 2734321 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.44 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 56.46 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.62 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.21 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.68 |
Solubility | 4.42 mg/ml ; 0.0209 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.96 |
Solubility | 2.32 mg/ml ; 0.011 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.58 |
Solubility | 55.5 mg/ml ; 0.263 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.97 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.48 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.6% | With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In 1,4-dioxane; at 100℃; for 1h; | To a suspension of methyl 6-chloro-5 -nitronicotinate (0.108 g, 0.499 mmol), l-Boc-pyrrole-2- boronic acid (0.210 g, 0.997 mmol), and trans-Dichlorobis(triphenylphosphine)palladium (II) (0.350 g, 0.499 mmol) in Dioxane (Volume: 2.3 mL) was added 2M Sodium carbonate (0.798 mL, 1.596 mmol) at 23 0C. The reaction was stirred at 100 0C for 1 hr. The resulting suspension was filtered and rinsed with dioxane and H2O. The filtrate was diluted with EtOAc (20 mL) and the layers were separated. The organic phase was washed with saturated NaHCpsi3 and brine, dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo. The resulting crude material was purified via medium pressure chromatography using a gradient eluant Of CH2Cl2ZMeOH. The appropriate fractions were combined and concentrated via rotary evaporation to provide methyl 6-(l -(tert-butoxycarbonyl)- IH- pyrrol-2-yl)-5 -nitronicotinate (0.0738 g, 0.212 mmol, 42.6 percent yield) as an orange gummy solid. 1H NMR (400 MHz, DMSO-J6) delta ppm 1.32 (s, 9 H) 3.96 (s, 3 H) 6.41 (t, J=3.28 Hz, 1 H) 6.65 (dd, J=3.28, 1.77 Hz, 1 H) 7.50 (dd, J=3.28, 1.77 Hz, 1 H) 8.82 (d, J=I.77 Hz, 1 H) 9.33 (d, J=I.77 Hz, 1 H). ESI-MS: m/z 348.2 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; cesium fluoride; In N,N-dimethyl-formamide; at 20 - 60℃; for 3h;Inert atmosphere; | General procedure: 18 (138.5mg, 0.47mmol) was added to a solution of boronic acid (304.5mg, 1.44mmol), cesium fluoride (303mg, 1.99mmol), and PdCl2(dppf) (81.2mg, 0.10mmol) in dry DMF (5mL) at room temperature under argon. The reaction mixture was heated at 60C for 3h, then neutralized with ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (silica gel, AcOEt/n-hexane=1:4) to give 23 (129mg, 72%). Compounds 22 and 24 were synthesized similarly from compounds 14 and 21, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; bis(dibenzylideneacetone)-palladium(0); CyJohnPhos; In ethanol; water;Inert atmosphere; Reflux; | 4-Iodo-1,2-dimethoxybenzene (5; 16.7 g, 63.3 mmol) was dissolved in EtOH (63 mL), Boc-pyrroleboronic acid (4; 20.0 g, 94.8 mmol, 1.5 equiv) was added to the solution followed by the addition of an aqueous solution of K2CO3 (17.5 g, 126.8 mmol, 2 equiv; in 63 mL H2O). Under a constant flow of N2, CyJohnPhos (378 mg, 2 mol%) was added followed by Pd(dba)2 (364 mg, 1 mol%). The reaction mixture was vigorously stirred and heated under reflux for 4-5 h. The reaction mixture was cooled to r.t. and extracted with hexane (3 x 100 mL). The organic layer was dried over Na2SO4 and evaporated. To the residue (contains aryl iodide, Boc-pyrrole and product ~1:1:1) was added freshly prepared (from Na and MeOH) NaOMe solution (~1 M in MeOH, 3-5 equiv) and the mixture was left overnight. The reaction mixture was diluted with H2O and extracted with Et2O (3 x 100 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated. The residue was triturated with hexane and filtered off to give pure enough compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; XPhos; In butan-1-ol; for 2h;Inert atmosphere; | General procedure: To a flame-dried 5 mL microwave vial flask equipped with a magnetic stir bar was added N-Boc-pyrrole-2-boronic acid (316 mg,1.5 mmol, 1.5 equiv), Pd(OAc)2 (4.5 mg, 0.02 mmol, 0.02 equiv), XPhos (19.0 mg, 0.04 mmol, 0.04 equiv), K3PO4 (424 g, 2.0 mmol, 2.0 equiv), and aryl bromide (1.0 mmol, 1.0 equiv). The flask was evacuated and backfilled with nitrogen three times, and then the gas line adapter was quickly replaced with a rubber septum and a balloon of nitrogen. To the flask was added degassed (by sonicationfor 30 min with N2 sparging), anhydrous n-butanol [2 mL (0.5M in ArBr)]. The heterogeneous reaction mixture was stirred vigorously for 2 h and then poured into ethyl acetate (~20 mL). This mixture was filtered through a pad of silica and concentrated under reduced pressure by rotary evaporation. This product was used without further purification. |
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