Structure of 95-15-8
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Surveying the scope of aromatic decarboxylations catalyzed by prenylated-flavin dependent enzymes
Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh
Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.
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Purchased from AmBeed: 27916-43-4 ; 2438-05-3 ; 501-89-3 ; 42287-94-5 ; 776-79-4 ; 53473-36-2 ; 7251-61-8 ; 42287-97-8 ; 1621-91-6 ; 37718-11-9 ; 288-13-1 ; 86-73-7 ; 104-53-0 ; 2018-90-8 ; 87-66-1 ; 135-19-3 ; 1664-57-9 ; 289-80-5 ; 693-95-8 ; 55-22-1 ; 102-93-2 ; 1477-50-5 ; 1632-76-4 ; 4780-79-4 ; 16642-79-8 ; 3581-89-3 ; 501-97-3 ; 771-50-6 ; 98-98-6 ; 619-64-7 ; 100-51-6 ; 402-45-9 ; 59-67-6 ; 93-60-7 ; 273-53-0 ; 2084-13-1 ; 51-17-2 ; 2459-09-8 ; 2459-07-6 ; 95-16-9 ; 459-31-4 ; 90-05-1 ; 150-76-5 ; 103-25-3 ; 271-44-3 ; 6293-56-7 ; 2550-26-7 ; 288-32-4 ; 501-52-0 ; 2001-32-3 ; 1592-38-7 ; 95-15-8 ; 91-19-0 ; 1122-61-8 ; 3724-19-4 ; 20173-24-4 ; 118-31-0 ; 6125-24-2 ; 60-12-8 ; 90-15-3 ; 120-72-9 ; 822-36-6 ; 288-47-1 ; 288-42-6 ; 2038-57-5 ; 38628-51-2 ; 1929-29-9 ; 15009-91-3 ; 1505-50-6 ; 581-40-8 ; 616-47-7 ; 1571-33-1
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CAS No. : | 95-15-8 |
Formula : | C8H6S |
M.W : | 134.20 |
SMILES Code : | C1=CSC2=C1C=CC=C2 |
MDL No. : | MFCD00005864 |
InChI Key : | FCEHBMOGCRZNNI-UHFFFAOYSA-N |
Pubchem ID : | 7221 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H319-H372-H410 |
Precautionary Statements: | P501-P273-P260-P270-P264-P280-P391-P314-P337+P313-P305+P351+P338-P301+P312+P330 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
28.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.12 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.64 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.78 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.89 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.38 |
Solubility | 0.0562 mg/ml ; 0.000419 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.38 |
Solubility | 0.0557 mg/ml ; 0.000415 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.31 |
Solubility | 0.0659 mg/ml ; 0.000491 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 |
Yes |
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) |
Yes |
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 |
-4.9 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 |
2.0 |
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 |
0.0 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) |
1.61 |
* 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 |
---|---|---|
100% | With bromine; potassium acetate; In dichloromethane; | In the DCM solvent, in the presence of potassium acetate, benzothiophene (11) was brominated using bromine the benzothiophene. A white solid of compound (12) was obtained in a yield of 100%. In addition, equation (1) when manufacturing the compound shown, compound (11) gives the desired compound X can be replaced. |
99% | With bromine; In chloroform; at 20℃; for 19.5h; | A solution of 18 g (134 mmol) of benzo[b]thiophene in 200 mL of chloroform was stirred and to this mixture was added 42.9 g (13.7 mL, 268 mmol) of bromine in 100 mL of chloroform dropwise at RT over 1.5 h. After stirring for 18 h, solid NaHCO3 was added to neutralize the hydrobromic acid. The organic layer was washed with water and Na2S2O8 and dried (MgSO4). On evaporation of the solvent solid was obtained which was crystallized from methanol to give 38.8 g (99%) of 2,3-dibromobenzo[b]thiophene. |
90% | With bromine; In chloroform; at 0℃; for 12h; | Benzo[b]thiophene (10 g, 74.5 mmol) was dissolved in 250 ml of chloroform. The resulting solution was cooled down to 0C and bromine (7.87 ml, 152.8 mmol) was added. The mixture was stirred for 12h. The reaction mixture was poured into water and extracted with chloroform. The organic layer was separated, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to afford (3) as a white solid, yield 90%. 1H NMR (CDCl3, 400MHz) 7.76-7.74 (d, J=8.8Hz, 1H), 7.73-7.71 (d, J=8Hz, 1H), 7.45-7.41 (t, J=7.6Hz, 1H), 7.41-7.36 (t, J=8Hz, 1H) ppm. |
84% | With bromine; potassium acetate; In dichloromethane; at 20℃;Reflux; | To a CH2Cl2 solution (50 mL) of benzo[b]thiophene (14, 5.00 g, 37.3 mmol) and KOAc (7.30 g, 74.6 mmol) was added Br2 (3.8 mL, 74.6 mmol) at 20 C, and the solution was heated under reflux for 24 h. To the solution was added a satd solution of Na2S2O3 and NaHCO3. The organic and the aqueous layer were separated, and the latter was extracted with CH2Cl2 (3*30 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash silica column chromatography (pure heptanes) to yield 15a as a white solid (9.1 g, 84%). The spectroscopic data were identical with those reported.<ce-sup primary_key="ce-sup-35854493-none">17,18 |
80% | With bromine; In chloroform; at 20℃; for 24h; | Chloroform (200 mL) was used to dissolve benzo[b]thiophene(140 mmol) followed by drop wise addition of Br2 (310 mmol). The mixture was stirred at room temperaturefor 24 h. Washing of the resultant solution was done withNa2S2O3 aqueous solution and organic layer was separatedby using ethyl acetate. It was dried and concentrated withanhydrous MgSO4. The product was re-precipitated usingn-hexane in excess which resulted in the formation of whitecolored product. |
16.5 g (57 mmol, 28%) | With bromine; In chloroform; | A. 2,3-Dibromobenzo[b]thiophene STR16 Benzothiophene (26.8 g, 0.2 mol) was dissolved in 150 mL CHCl3 and treated with a solution of bromine (64 g, 0.4 mol) in 75 mL CHCl3 dropwise over an hour. The reaction was allowed to stir overnight then cautiously quenched with saturated aqueous Na2 CO3 until no gas evolution was evident. The layers were separated and the organic layer was first washed with saturated aqueous Na2 CO3 then with water. It was dried over MgSO4 and concentrated under vacuum to a solid. Recrystallized from MeOH to obtain 16.5 g (57 mmol, 28%) of a white fluffy solid. 1 H NMR (CDCl3) δ7.77-7.71 (m, 2H), 7.46-7.38 (m, 2H). |
With bromine; In chloroform; | A. Preparation of 2,3-dibromobenzo[b]thiophene. A solution of 64 g of bromine in 50 ml of chloroform was added to a solution of 26.8 g of 1-benzothiophene in 150 ml of chloroform. After stirring for approximately 18 hours, the reaction mixture was washed sequentially with 0.1N sodium hydroxide, 0.1N aqueous sodium thiosulfate, and water. The organic layer was dried over magnesium sulfate and evaporated to dryness. The residue was crystallized twice from methanol to provide 20.54 g of the desired subtitled intermediate, m.p. 57-59 C. Analysis for C8 H4 Br2 S; Calculated: C, 32.91; H, 1.38; Found: C, 32.72; H, 1.49. | |
16.5 g (57 mmol, 28%) | With bromine; In CHCl3and; CHCl3dropwise; | A. 2,3-Dibromobenzo[b]thiophene. Benzothiophene (26.8 g, 0.2 mol) was dissolved in 150 mL CHCl3and treated with a solution of bromine (64 g, 0.4 mol) in 75 mL CHCl3dropwise over an hour. The reaction was allowed to stir overnight then cautiously quenched with saturated aqueous Na2CO3until no gas evolution was evident. The layers were separated and the organic layer was first washed with saturated aqueous Na2CO3then with water. It was dried over MgSO4and concentrated under vacuum to a solid. Recrystallized from MeOH to obtain 16.5 g (57 mmol, 28%) of a white fluffy solid. 1H NMR (CDCl3) δ 7.77-7.71 (m, 2H), 7.46-7.38 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydroxide; bromine; In chloroform; | Synthesis of (R,R) [3,4-bis(2',5'-dimethylphospholanyl)]-benzo[b]thiophene Stage a: Synthesis of 2,3-dibromo-benzo[b]thiophene A solution of Br2(21.1 mL) in CHCl3 (65 mL) was dropped into a solution of benzo[b]thiophene (26.4 g) in CHCl3 (120 mL), under stirring, at a temperature of 0 C. The progress of the reaction was controlled in TLC (hexane) up to the disappearance of the starting product: Rf (thianaphthene): 0.33, Rf (2,3-dibromobenzothiophene): 0.5. The mixture was then poured into aqueous, NaOH; the organic phase was separated, washed twice with a solution of 10% NaOH and once with water, and then dehydrated on Na2SO4. The solvent was evaporated to yield the 2,3-dibromo-benzo[b]thiophene as a white solid (52 g) (yield 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With proton-exchanged montmorillonite; at 20℃; | General procedure: To a mixture of 12 (66 mg, 0.366 mmol) and arenes or heteroarenes(1 mL) was added H-mont (260 mg). The reaction mixturewas stirred at room temperature until the TLC indicated the consumptionof the starting material. The mixture was filtered toremove H-mont, and the filtrate was evaporated under reducedpressure. The residue was purified by flash chromatography (petroleumether/ethyl acetate 200:1 to 10:1) to give the product.Following the procedure, 14ceg were prepared. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With n-butyllithium; In tetrahydrofuran; hexane; at -30 - 20℃; for 6h;Inert atmosphere; | General procedure: To a solution of benzo[b]thiophene (8) (2.15g, 16.0mmol) in 20ml dry THF under an argon atmosphere at?30°C, n-BuLi (10.0ml, 16.0mmol, 1.6M n-hexane) was added slowly. The mixture was treated with the corresponding ester and stirred at room temperature. After quenching with saturated aqueous NH4Cl-solution, the residue was extracted with CHCl3. The organic phase was dried (Na2SO4) and the solvent evaporated. |
Tags: 95-15-8 synthesis path| 95-15-8 SDS| 95-15-8 COA| 95-15-8 purity| 95-15-8 application| 95-15-8 NMR| 95-15-8 COA| 95-15-8 structure
A137891 [3541-37-5]
Benzo[b]thiophene-2-carbaldehyde
Similarity: 0.80
A304752 [55219-11-9]
Benzo[b]thiophene-2-carbonitrile
Similarity: 0.80
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H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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