AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Feb 082018
 

Abstract Image

Unconventional Method for Synthesis of 3-Carboxyethyl-4-formyl(hydroxy)-5-aryl-N-arylpyrazoles

 Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil
 Departamento de Química, Universidade Federal de Santa Maria (UFSM), 97110-970 Santa Maria, RS, Brazil
§ Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), 295070-560 Caxias do Sul, RS, Brazil
J. Org. Chem.201782 (23), pp 12590–12602
DOI: 10.1021/acs.joc.7b02361
Publication Date (Web): November 2, 2017
*E-mail: farosa@uem.br

Abstract

An alternative highly regioselective synthetic method for the preparation of 3,5-disubstituted 4-formyl-N-arylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the cyclocondensation reaction of β-enamino diketones with arylhydrazines.

Structural modifications in the β-enamino diketone system allied to the Lewis acid carbonyl activator BF3 were strategically employed for this control. Also a one-pot method for the preparation of 3,5-disubstituted 4-hydroxymethyl-N-arylpyrazole derivatives from the β-enamino diketone and arylhydrazine substrates is described.

J. Org. Chem. 20178212590

4-Formyl-N-arylpyrazole substrates occupy a prominent position in the field of organic synthesis since they are key intermediates in obtaining a wide range of biologically active compounds. Because of the synthetic versatility of the 4-formyl-N-arylpyrazole skeleton, their synthesis has been extensively explored. In an extension of their previously published research,
Rosa and co-workers at Universidade Estadual de Maringá described a one-pot synthetic method that regioselectively produced 3,5-disubstituted-4-formyl-N-arylpyrazoles . The β-enamino diketone starting materials were readily synthesized via published procedures. High regioselectivity was secured via the use of BF3·OEt2 as the carbonyl activator and a bulky amine as the enamine component. Acetonitrile proved to be the most suitable solvent for the reaction.
After an aqueous workup, the desired pyrazoles were obtained in excellent yields. A variety of functional groups were tolerated on the two aryl substituents. This operationally simple procedure afforded the 4-formyl-N-arylpyrazoles in high yields, regioselectively. Furthermore, the formyl group could be reduced in situ with sodium borohydride to generate the corresponding 4-hydroxymethyl-N-arylpyrazoles.
STR1 STR2

3-(Ethoxycarbonyl)-4-formyl-5-(4-nitrophenyl)-1-phenyl-1H-pyrazole (3a)

Light yellow solid; yield: 0.150 g (82%); mp 147.0–149.2 °C;
1H NMR (300.06 MHz, CDCl3) δ (ppm) 1.47 (t, 3H, J = 7.1 Hz, O–CH2–CH3), 4.54 (q, 2H, J = 7.1 Hz, O–CH2-CH3), 7.19–7.25 (m, 2H, Ph), 7.32–7.43 (m, 3H, Ph), 7.48 (d, 2H, J = 8.9 Hz, 4-NO2C6H4), 8.19 (d, 2H, J = 8.9 Hz, 4-NO2C6H4), 10.57 (s, 1H, CHO);
13C NMR (75.46 MHz, CDCl3) δ (ppm) 14.4 (O–CH2CH3), 62.3 (O-CH2–CH3), 122.0 (C4), 123.5 (4-NO2C6H4), 125.9 (Ph), 129.5 (Ph), 129.6 (Ph), 131.8 (4-NO2C6H4), 134.1 (4-NO2C6H4), 137.8 (Ph), 143.5 (C5), 145.0 (C3), 148.4 (4-NO2C6H4), 161.5 (COOEt), 186.6 (CHO);
HRMS (ESI+): calcd for C19H16N3O5+, [M+H]+: 366.1084, found 366.1101.
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Feb 082018
 

 

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC03619A, Communication
Yahui Li, Zechao Wang, Xiao-Feng Wu
A sustainable procedure for the synthesis of various alkyl arylacetates from benzyl alcohols has been developed

A sustainable procedure toward alkyl arylacetates: palladium-catalysed direct carbonylation of benzyl alcohols in organic carbonates

Author affiliations

Abstract

A sustainable procedure for the synthesis of various alkyl arylacetates from benzyl alcohols has been developed. With palladium as the catalyst and organic carbonates as the green solvent and in situ activator, benzyl alcohols were carbonylated in an efficient manner without any halogen additives.

Ethyl 2-phenylacetate

1H NMR (300 MHz, Chloroform-d) δ 7.32 – 7.08 (m, 5H), 4.08 (q, J = 7.1 Hz, 2H), 3.54 (s, 2H), 1.18 (t, J = 7.1 Hz, 3H).

13C NMR (75 MHz, CDCl3) δ 171.61, 134.17, 129.24, 128.54, 127.03, 60.85, 41.45, 14.18.

 

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Feb 072018
 

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AMISELIMOD

UNII-358M5150LY; CAS 942399-20-4; 358M5150LY; MT-1303; Amiselimod, MT-1303

Molecular Formula: C19H30F3NO3
Molecular Weight: 377.448 g/mol

 

2-amino-2-[2-[4-heptoxy-3-(trifluoromethyl)phenyl]ethyl]propane-1,3-diol

Phase II Crohn’s disease; Multiple sclerosis; Plaque psoriasis

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AMISELIMOD HYDROCHLORIDE

  • Molecular FormulaC19H31ClF3NO3
  • Average mass413.902 Da
1,3-Propanediol, 2-amino-2-[2-[4-(heptyloxy)-3-(trifluoromethyl)phenyl]ethyl]-, hydrochloride (1:1)
2-Amino-2-{2-[4-(heptyloxy)-3-(trifluoromethyl)phenyl]ethyl}-1,3-propanediol hydrochloride (1:1)
942398-84-7 [RN]
MT-1303
UNII-AY898D6RU1
2-amino-2-[2-[4-(heptyloxy)-3-(trifluoromethyl)phenyl]ethyl]-1,3-propanediol, monohydrochloride
  • Originator Mitsubishi Tanabe Pharma Corporation
  • Class Propylene glycols; Small molecules
  • Mechanism of Action Immunosuppressants; Sphingosine-1-phosphate receptor antagonist

Highest Development Phases

  • Phase II Crohn’s disease; Multiple sclerosis; Plaque psoriasis
  • Phase I Autoimmune disorders; Inflammation; Systemic lupus erythematosus
  • No development reported Inflammatory bowel diseases

Most Recent Events

  • 04 Nov 2017 No recent reports of development identified for phase-I development in Autoimmune-disorders in Japan (PO, Capsule)
  • 04 Nov 2017 No recent reports of development identified for phase-I development in Autoimmune-disorders in USA (PO, Capsule)
  • 04 Nov 2017 No recent reports of development identified for phase-I development in Inflammation in Japan (PO, Capsule)
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Amiselimod, also known as MT1303, is a potent and selective immunosuppressant and sphingosine 1 phosphate receptor modulator. Amiselimod may be potentially useful for treatment of multiple sclerosis; inflammatory diseases; autoimmune diseases; psoriasis and inflammatory bowel diseases. Amiselimod is currently being developed by Mitsubishi Tanabe Pharma Corporation

Mitsubishi Tanabe is developing amiselimod, an oral sphingosine-1-phosphate (S1P) receptor antagonist, for treating autoimmune diseases, primarily multiple sclerosis, psoriasis and inflammatory bowel diseases, including Crohn’s disease.

WO2007069712

EU states expire 2026, and

Expire in the US in June 2030 with US154 extension.

Inventors Masatoshi KiuchiKaoru MarukawaNobutaka KobayashiKunio Sugahara
Applicant Mitsubishi Tanabe Pharma Corporation

In recent years, calcineurin inhibitors such as cyclosporine FK 506 have been used to suppress rejection of patients receiving organ transplantation. While doing it, certain calcineurin inhibitors like cyclosporin can cause harmful side effects such as nephrotoxicity, hepatotoxicity, neurotoxicity, etc. For this reason, in order to suppress rejection reaction in transplant patients, development of drugs with higher safety and higher effectiveness is advanced.

[0003] Patent Documents 1 to 3 are useful as inhibitors of (acute or chronic) rejection in organ or bone marrow transplantation and also useful as therapeutic agents for various autoimmune diseases such as psoriasis and Behcet’s disease and rheumatic diseases 2 aminopropane 1, 3 dioly intermediates are disclosed.

[0004] One of these compounds, 2-amino-2- [2- (4-octylphenel) propane] 1, 3 diol hydrochloride (hereinafter sometimes referred to as FTY 720) is useful for renal transplantation It is currently under clinical development as an inhibitor of rejection reaction. FTY 720 is phosphorylated by sphingosine kinase in vivo in the form of phosphorylated FTY 720 [hereinafter sometimes referred to as FTY 720-P]. For example, 2 amino-2-phosphoryloxymethyl 4- (4-octafil-el) butanol. FTY720 – P has four types of S1 P receptors (hereinafter referred to as S1 P receptors) among five kinds of sphingosine – 1 – phosphate (hereinafter sometimes referred to as S1P) receptors It acts as an aggroove on the body (other than S1P2) (Non-Patent Document 1).

[0005] It has recently been reported that S1P1 among the S1P receptors is essential for the export of mature lymphocytes with thymus and secondary lymphoid tissue forces. FTY720 – P downregulates S1P1 on lymphocytes by acting as S1P1 ghost. As a result, the transfer of mature lymphocytes from the thymus and secondary lymphatic tissues is inhibited, and the circulating adult lymphocytes in the blood are isolated in the secondary lymphatic tissue to exert an immunosuppressive effect Has been suggested (

Non-Patent Document 2).

[0006] On the other hand, conventional 2-aminopropane 1, 3 dioly compounds are concerned as transient bradycardia expression as a side effect, and in order to solve this problem, 2-aminopropane 1, 3 diiori Many new compounds have been reported by geometrically modifying compounds. Among them, as a compound having a substituent on the benzene ring possessed by FTY 720, Patent Document 4 discloses an aminopropenol derivative as a S1P receptor modulator with a phosphate group, Patent Documents 5 and 6 are both S1P Discloses an amino-propanol derivative as a receptor modulator. However, trihaloalkyl groups such as trifluoromethyl groups are not disclosed as substituents on the benzene ring among them. In any case, it is currently the case that it has not yet reached a satisfactory level of safety as a pharmaceutical.

Patent Document 1: International Publication Pamphlet WO 94 Z 08943

Patent Document 2: International Publication Pamphlet WO 96 Z 06068

Patent Document 3: International Publication Pamphlet W 0 98 z 45 429

Patent Document 4: International Publication Pamphlet WO 02 Z 076995

Patent document 5: International public non-fret WO 2004 Z 096752

Patent Document 6: International Publication Pamphlet WO 2004 Z 110979

Non-patent document 1: Science, 2002, 296, 346-349

Non-patent document 2: Nature, 2004, 427, 355-360

Reference Example 3

5 bromo 2 heptyloxybenzonitrile

(3- 1) 5 Synthesis of bromo-2 heptyloxybenzonitrile (Reference Example Compound 3- 1)

1-Heptanol (1.55 g) was dissolved in N, N dimethylformamide (24 ml) and sodium hydride (0.321 g) was added at room temperature. After stirring for 1 hour, 5 bromo-2 fluoborosyl-tolyl (2.43 g) was added and the mixture was further stirred for 50 minutes. The reaction solution was poured into water, extracted with ethyl acetate, washed with water, saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. After eliminating the 5 bromo 2 fluconate benzonitrile as a raw material, the reaction was carried out again under the same conditions and purification was carried out by silica gel column chromatography (hexane: ethyl acetate = 50: 1 to 5: 1) to obtain the desired product (3.10 g ) As a colorless oil.

– NMR (CDCl 3) δ (ppm): 0.89 (3H, t, J = 6.4 Hz), 1.24-1.35 (6H, m

J = 8.8 Hz), 1.48 (2H, quint, J = 7.2 Hz), 1.84 7.59 (1 H, dd, J = 8.8, 2.4 Hz), 7.65 (1 H, d, J = 2.4 Hz).

Example 1

2 Amino 2- [2- (4-heptyloxy-3 trifluoromethylph enyl) propane-1, 3-diol hydrochloride

(1 – 1) {2, 2 Dimethyl 5- [2- (4 hydroxy 3 trifluoromethylfuethyl) ethyl] 1,3 dioxane 5 mercaptothenylboronic acid t butyl ester (synthesis compound 1 1)

Reference Example Compound 2-5 (70.3 g) was dissolved in tetrahydrofuran (500 ml), t-butoxycallium (13.Og) was added, and the mixture was stirred for 1 hour. To the mixed solution was dropwise added a solution of the compound of Reference Example 1 (15.Og) in tetrahydrofuran (100 ml) under ice cooling, followed by stirring for 2 hours under ice cooling. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with water, saturated brine, dried with anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: D to obtain 31. Og of a pale yellow oily matter.) The geometric isomer ratio of the obtained product was (E : Z = 1: 6).

This pale yellow oil was dissolved in ethyl acetate (200 ml), 10% palladium carbon (3.00 g) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 7 hours. After purging the inside of the reaction vessel with nitrogen, the solution was filtered and the filtrate was concentrated. The residue was washed with diisopropyl ether to obtain the desired product (2.2 g) as a colorless powder.

1 H-NMR (CDCl 3) δ (ppm): 1. 43 (3H, s), 1.44 (3H, s), 1. 47 (9H, s), 1

(2H, m), 91- 1. 98 (2H, m), 2. 50-2.66 (2H, m), 3. 69 (2H, d, J = Il. 6 Hz), 3. 89 J = 8.2 Hz), 7. 22 (1 H, dd J = 8 Hz), 5. 02 (1 H, brs), 5. 52 . 2, 1. 7 Hz), 7. 29 (1 H, d, J = l. 7 Hz).

(1-2) {2,2 Dimethyl-5- [2- (4heptyloxy-3 trifluoromethyl) ethyl] 1,3 dioxane 5-mercaptobutyric acid t-butyl ester Synthesis (compound 1 2)

Compound 1-1 (510 mg) was dissolved in N, N dimethylformamide (10 ml), potassium carbonate (506 mg) and n-heptyl bromide (0.235 ml) were added and stirred at 80 ° C. for 2 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with water and saturated brine, dried with anhydrous sulfuric acid

The resultant was dried with GENSCHUM and the solvent was distilled off under reduced pressure to obtain the desired product (640 mg) as a colorless oil.

– NMR (CDCl 3) δ (ppm): 0.89 (3H, t, J = 6.8 Hz), l.30-1.37 (6H, m

(2H, m), 1.91-1.98 (2H, m), 1.42-1.50 (2H, m), 1.42 (3H, s), 1.44 (3H, s), 1.47 J = 16.6 Hz), 4.00 (2H, t, J = 6.4 Hz), 4.9 8 (2H, d, J = 11.6 Hz), 3.69 1 H, brs), 6.88 (1 H, d, J = 8.5 Hz), 7.26 – 7.29 (1 H, m), 7.35 (1 H, d, J = 1.5 Hz).

(1-3) Synthesis of 2-amino-2- [2- (4heptyloxy 3 trifluoromethyl) ethyl] propane 1, 3 diol hydrochloride (Compound 1- 3)

Compound 12 (640 mg) was dissolved in ethanol (15 ml), concentrated hydrochloric acid (3 ml) was caught and stirred at 80 ° C. for 2 hours. The reaction solution was concentrated, and the residue was washed with ethyl ether to give the desired product (492 mg) as a white powder.

MS (ESI) m / z: 378 [M + H]

– NMR (DMSO-d) δ (ppm): 0.86 (3H,

6 t, J = 6.8 Hz), 1.24 – 1.39 (6

(4H, m), 3.51 (4H, d, J = 5. lHz), 4.06 (2H, m), 1.39-1.46 (2H, m), 1.68-1.78 (4H, m), 2.55-2.22 , 7.32 (2H, t, J = 5.1 Hz), 7.18 (1 H, d, J = 8.4 Hz), 7.42 – 7.45 (2 H, m), 7.76 (3 H, brs;).

PATENT

WO 2009119858

JP 2011136905

WO 2017188357

PATENT

WO-2018021517

Patent Document 1 discloses 2-amino-2- [2- (4-heptyloxy-3-trifluoromethylphenyl) ethyl] propane- 1,3 which is useful as a medicine excellent in immunosuppressive action, rejection- – diol hydrochloride is disclosed.
The production method includes the step of reducing 4-heptyloxy-3-trifluoromethylbenzoic acid (Ia) to 4-heptyloxy-3-trifluoromethylbenzyl alcohol (IIa). However, until now, there has been a problem such that the conversion is low and the by-product (IIa ‘) in which the trifluoromethyl group is reduced together with the compound (IIa) is generated in this step.

 

[Chemical formula 1]

 

 In particular, since a series of analogous substances derived from by-products (IIa ‘) are difficult to be removed in a later process, it is necessary to suppress strict production thereof in the manufacture of drug substances requiring high quality there were.

Patent Document 1: WO2007 / 069712

[Chemical formula 3]

(2-amino-2- [2- (4-heptyloxy-3-trifluoromethylphenyl) ethyl] propane- 1,3-diol hydrochloride) From
the compound (IIa), the following scheme Based on the route, 2-amino-2- [2- (4-heptyloxy-3-trifluoromethylphenyl) ethyl] propane-1,3-diol hydrochloride was prepared.

 

[Chemical Formula 9]

STR1

 

Example 2
Synthesis of 4-heptyloxy-3-trifluoromethylbenzyl chloride (Step A) A
few drops of N, N-dimethylformamide was added to a solution of compound (IIa) (26.8 g) in methylene chloride (107 mL), and 0 At 0 ° C., thionyl chloride (8.09 mL) was added dropwise. The mixture was stirred at the same temperature for 2 hours, and water (50 mL) was added to the reaction solution. The organic layer was separated and extracted, washed with water (50 mL), saturated aqueous sodium bicarbonate solution (70 mL), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give 4-heptyloxy-3-trifluoromethylbenzyl Chloride (28.3 g) as white crystals.
1H-NMR (CDCl 3) δ (ppm): 0.89 (3H, t, J = 6.5 Hz), 1.26-1.54 (8H, m), 1.77-1.86 (2H, m , 4.49 (2H, t, J = 6.4 Hz), 4.56 (2H, s), 6.96 (IH, d, J = 8.6 Hz), 7.49 (IH, dd, J = 2.0 Hz, 8.5 Hz), 7.58 (1 H, d, J = 1.9 Hz)

 

Example 3
Synthesis of dimethyl (4-heptyloxy-3-trifluoromethylbenzyl) phosphonate (Step B) To
a solution of N, N (3-trifluoromethylbenzyl ) phosphonate of 4-heptyloxy-3-trifluoromethylbenzyl chloride (6.00 g, 19.4 mmol) (2.57 g, 23.3 mmol), cesium carbonate (7.60 g, 23.3 mmol) and tetrabutylammonium iodide (7.54 g, 20.4 mmol) were added to a dimethylformamide (36 mL) And the mixture was stirred at 25 ° C. for 1 day. Toluene (36 mL) and water (18 mL) were added for phase separation, and the resulting organic layer was washed twice with a mixture of N, N-dimethylformamide (18 mL) and water (18 mL). After concentration under reduced pressure, column purification using hexane and ethyl acetate gave 4.71 g of dimethyl (4-heptyloxy-3-trifluoromethylbenzyl) phosphonate.
1
H-NMR (CDCl 3) δ (ppm): 0.89 (3 H, t, J = 6.9 Hz), 1.20 – 1.41 (6 H, m) , 1.43-1.49 (2H, m), 1.72-1.83 (2H, m), 3.09 (IH, s), 3.14 (IH, s), 3.68 (3H , 7.41 – 7.44 (2 H, t, J = 6.4 Hz), 6.94 (1 H, d, J = 8.4 Hz), 3.70 (3 H, s), 4.02 (2H, m)

 

Example 4
tert-Butyl (E) – {2,2-dimethyl-5- [2- (4-heptyloxy-3-trifluoromethylphenyl) vinyl] -1, 3-dioxan-5- yl} carbamate Ester synthesis (Step C) A
solution of dimethyl (1.18 g, 3.09 mmol ) (4-heptyloxy-3-trifluoromethylbenzyl) phosphonate in 1.25 mL of N, N- dimethylformamide and (2, -dimethyl-5-formyl-1,3-dioxan-5-yl) carbamic acid tert-butyl ester (961 mg, 3.71 mmol) in tetrahydrofuran (4 mL) was treated with potassium tert-butoxide (1.28 g, 4 mmol) in tetrahydrofuran (7 mL), and the mixture was stirred at 0 ° C. for 6 hours. Heptane (7 mL) and water (3 mL) were added and the layers were separated, and the obtained organic layer was washed twice with water (3 mL) and concentrated. Heptane was added and the mixture was cooled in an ice bath. The precipitated crystals were collected by filtration and dried under reduced pressure to give (E) – {2,2-dimethyl-5- [2- (4-heptyloxy- Phenyl) vinyl] -1, 3-dioxan-5-yl} carbamic acid tert-butyl ester.
1
H-NMR (CDCl 3) δ (ppm): 0.89 (3 H, t, J = 6.9 Hz), 1.29 – 1.38 (6 H, m) , 1.44 – 1.59 (17 H, m), 1.77 – 1.83 (2 H, m), 3.83 – 3.93 (2 H, m), 3.93 – 4.08 (4 H, J = 16.5 Hz), 6.48 (1 H, d, J = 16.5 Hz), 6.91 (1 H, d, J), 5.21 (1 H, brs), 6.10 J = 8.5 Hz), 7.44 (1 H, dd, J = 8.6, 2.1 Hz), 7.55 (1 H, d, J = 2.0 Hz)

 

Example 5
Synthesis of 2-amino-2- [2- (4-heptyloxy-3-trifluoromethylphenyl) ethyl] propane-1,3-diol hydrochloride (Step D)
(E) – {2, -dimethyl-5- [2- (4-heptyloxy-3-trifluoromethylphenyl) vinyl] -1,3-dioxan- 5-yl} carbamic acid tert-butyl ester (6.50 g, 12.6 mmol) Methanol (65 mL) solution was heated to 50 ° C., a solution of concentrated hydrochloric acid (2.55 g) in methanol (5.3 mL) was added dropwise, and the mixture was stirred at 60 ° C. for 6 hours. The mixture was cooled to around room temperature, 5% palladium carbon (0.33 g) was added thereto, and the mixture was stirred under a hydrogen gas atmosphere for 3 hours. After filtration and washing the residue with methanol (39 mL), the filtrate was concentrated and stirred at 5 ° C. for 1 hour. Water (32.5 mL) was added and the mixture was stirred at 5 ° C for 1 hour, and the precipitated crystals were collected by filtration. Washed with water (13 mL) and dried under reduced pressure to obtain 4.83 g of 2-amino-2- [2- (4-heptyloxy-3-trifluoromethylphenyl) ethyl] propane-1,3-diol hydrochloride .
MS (ESI) m / z: 378 [M + H]

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PATENTS

Patent ID

Patent Title

Submitted Date

Granted Date

US2017029378 KINASE INHIBITOR
2016-10-12
US2014296183 AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES
2014-06-17
2014-10-02
Patent ID

Patent Title

Submitted Date

Granted Date

US2017253563 KINASE INHIBITORS
2017-05-24
US9499486 Kinase inhibitor
2015-10-01
2016-11-22
US9751837 KINASE INHIBITORS
2015-10-01
2016-04-14
US8809304 Amine Compound and Use Thereof for Medical Purposes
2009-05-28
US2017209445 KINASE INHIBITORS
2015-10-01

////////////AMISELIMOD, Phase II, Crohn’s disease, Multiple sclerosis, Plaque psoriasis,  MT-1303,  MT1303,  MT 1303, Mitsubishi Tanabe Pharma Corporation, Mitsubishi , JAPAN, PHASE 2

CCCCCCCOC1=C(C=C(C=C1)CCC(CO)(CO)N)C(F)(F)F

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Jan 232018
 

Med. Chem. Commun., 2018, Advance Article
DOI: 10.1039/C7MD00656J, Research Article
Angela F. Ku, Gregory D. Cuny
Potent beta-1 and beta-2 adrenergic receptor antagonism via a conformationally restricted aporphine scaffold with defined stereochemistry has been developed.

Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors

 Author affiliations

Abstract

A series of (−)-nornuciferidine derivatives was synthesized and the non-natural enantiomer of the aporphine alkaloid was discovered to be a potent β1– and β2-adrenergic receptor ligand that antagonized isoproterenol and procaterol induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic analogues revealed that the conformationally restricted (6a-R,7-R)-7-hydroxyaporphine 2 (AK-2-202) was necessary for efficient receptor binding and antagonism.

STR1STR2STR3

(6aR,7R)-1,2-Dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-7-ol (2) To a solution of S2 (10 mg, 0.031 mmol) in THF (2 mL) was added 2 N NaOH(aq) (1 mL), and the mixture was stirred at 70 oC for 2 days. After being quenched with H2O (10 mL), the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (CH3OH/CH2Cl2, 5:95 to 10:90) to afford 2 (7.6 mg, 82%) as a pale yellow solid; mp 89−91 oC; [] 24 D +78 (c 0.58, CHCl3); 1H NMR (CDCl3, 500 MHz) 8.37−8.35 (1 H, m), 7.73−7.72 (1 H, m), 7.38−7.33 (2 H, m), 6.65 (1 H, s), 4.55 (1 H, d, J = 11.5 Hz), 3.88 (3 H, s), 3.67 (1 H, d, J = 11.5 Hz), 3.64 (3 H, s), 3.40−3.37 (1 H, m), 3.10−3.03 (1 H, m), 2.98 (1 H, td, J = 11.5, 3.5 Hz), 2.73 (1 H, d, J = 16.0 Hz); 13C NMR (CDCl3, 125 MHz) 152.5, 145.1, 139.0, 130.2, 129.4, 128.1, 127.8, 127.4, 125.9, 124.3, 123.1, 111.8, 72.0, 60.3, 59.0, 55.9, 42.0, 28.9; HRMS (ESI/Q-TOF) m/z [M + H]+ calculated for C18H20NO3 298.1438; found 298.1440

http://pubs.rsc.org/en/Content/ArticleLanding/2018/MD/C7MD00656J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FMD+%28RSC+-+Med.+Chem.+Commun.+latest+articles%29#!divAbstract

SIMILAR IN LIT

  • (-)-Nornuciferidine
  •  112494-69-6
    Molecular Weight297.35, C18 H19 N O3
    4H-​Dibenzo[de,​g]​quinolin-​7-​ol, 5,​6,​6a,​7-​tetrahydro-​1,​2-​dimethoxy-​, (6aS-​cis)​-
    S S ISOMER
    STR1
    http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.5b00007/suppl_file/ol5b00007_si_001.pdf

    Synthetic Studies of 7-Oxygenated Aporphine Alkaloids: Preparation of (−)-Oliveroline, (−)-Nornuciferidine, and Derivatives

    Department of Chemistry and Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Science and Research Building 2, Rm 549A, Houston, Texas 77204, United States
    Org. Lett.201517 (5), pp 1134–1137
    DOI: 10.1021/acs.orglett.5b00007

    Abstract

    Abstract Image

    7-Oxygenated aporphines 16 possessing anti-configurations have previously been reported. In order to explore their bioactivities, a synthesis was established by utilizing a diastereoselective reductive acid-mediated cyclization followed by palladium-catalyzed ortho-arylations. Moderate XPhos precatalyst loading (10 mol %) and short reaction times (30 min) were sufficient to mediate the arylations. Alkaloids 15 were successfully prepared, while (−)-artabonatine A was revised to syn-isomer 30. Consequently, (−)-artabonatine E likely also has a syn-configuration (31).

///////////AK-2-202, 

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Bio-derived production of cinnamyl alcohol via a three step biocatalytic cascade and metabolic engineering

 PROCESS, spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Bio-derived production of cinnamyl alcohol via a three step biocatalytic cascade and metabolic engineering
Jan 122018
 

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC03325G, Paper
Evaldas Klumbys, Ziga Zebec, Nicholas J. Weise, Nicholas J. Turner, Nigel S. Scrutton
Cascade biocatalysis and metabolic engineering provide routes to cinnamyl alcohol.

Bio-derived production of cinnamyl alcohol via a three step biocatalytic cascade and metabolic engineering

* Corresponding authors

Prof Nigel ScruttonScD, FRSC, FRSB

Professor of Enzymology and Biophysical Chemistry

Abstract

The construction of biocatalytic cascades for the production of chemical precursors is fast becoming one of the most efficient approaches to multi-step synthesis in modern chemistry. However, despite the use of low solvent systems and renewably resourced catalysts in reported examples, many cascades are still dependent on petrochemical starting materials, which as of yet cannot be accessed in a sustainable fashion. Herein, we report the production of the versatile chemical building block cinnamyl alcohol from the primary metabolite and the fermentation product L-phenylalanine. Through the combination of three biocatalyst classes (phenylalanine ammonia lyase, carboxylic acid reductase and alcohol dehydrogenase) the target compound could be obtained in high purity, demonstrable at the 100 mg scale and achieving 53% yield using ambient temperature and pressure in an aqueous solution. This system represents a synthetic strategy in which all components present at time zero are biogenic and thus minimises damage to the environment. Furthermore we extend this biocatalytic cascade by its inclusion in an L-phenylalanine overproducing strain of Escherichia coli. This metabolically engineered strain produces cinnamyl alcohol in mineral media using glycerol and glucose as the carbon sources. This study demonstrates the potential to establish green routes to the synthesis of cinnamyl alcohol from a waste stream such as glycerol derived, for example, from lipase treated biodiesel.

(R)-3-amino-3-(3-fluorophenyl)propanoic acid (1c) 1H NMR (CDCl3): δ 7.16-7.31 (m, 5H, ArH), 6.50-6.54 (d, 1H, J = 16 Hz, C=CH), 6.23-6.30 (dt, 1H, J = 16, 8 Hz, C=CHCH2 ), 4.21-4.23 (dd, 2H, J = 8, 4 Hz, C=CHCH2); 13C NMR (CDCl3): 136.70, 131.09, 128.60, 128.54, 127.69, 126.48, 63.65.

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////////////cinnamyl alcohol,  biocatalytic, metabolic engineering

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Persulfurated Coronene: A New Generation of “Sulflower”

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Persulfurated Coronene: A New Generation of “Sulflower”
Dec 062017
 

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2073844-77-4
C24 S12, 673.04
Coroneno[1,​12-​cd:2,​3-​cd‘:4,​5-​cd”:6,​7-​c”’d”’:8,​9-​c””d””:10,​11-​c””’d””’]​hexakis[1,​2]​dithiole

A persulfurated coronene, a molecule dubbed a “sulflower” for its resemblance to a sunflower, bloomed this year. It’s the first fully sulfur-substituted polycyclic aromatic hydrocarbon and only the second member of a new class of circular heterocyclic carbon sulfide compounds, after the synthesis of octathio[8]circulene a decade ago.

Chemists hope to create other class members, including the simplest one, persulfurated benzene, for use in battery cathodes and other electronic materials.

A team led by Xinliang Feng of Dresden University of Technology and Klaus Müllen of the Max Planck Institute for Polymer Research created the sulflower (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.6b12630).

http://pubs.acs.org/doi/abs/10.1021/jacs.6b12630

 

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Synthesis of persulfuratedcoronene (5, PSC)

5 (82 mg) as dark red solid in 61% yield. HR-MS (HR-MALDI-TOF) m/z: Calcd. for C24S12: 671.6629; Found 671.6648 [M]+; Elem. Anal. calcd. for C24S12: C, 42.83; S, 57.17. Found: C, 42.87; S, 57.13.

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Persulfurated Coronene: A New Generation of “Sulflower”

 Department of Chemistry and Food Chemistry, Center for Advancing Electronics Dresden, Technische Universität Dresden, 01062 Dresden, Germany
§ Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
 Institute for Materials Science, Max Bergmann Center of Biomaterials, and Center for Advancing Electronics Dresden, TU Dresden, 01069 Dresden, Germany
 Dipartimento di Chimica, Materiali ed Ingegneria Chimica ‘G. Natta’, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy
J. Am. Chem. Soc.2017139 (6), pp 2168–2171
DOI: 10.1021/jacs.6b12630
Publication Date (Web): January 27, 2017
Copyright © 2017 American Chemical Society
Abstract Image

We report the first synthesis of a persulfurated polycyclic aromatic hydrocarbon (PAH) as a next-generation “sulflower.” In this novel PAH, disulfide units establish an all-sulfur periphery around a coronene core. The structure, electronic properties, and redox behavior were investigated by microscopic, spectroscopic and electrochemical methods and supported by density functional theory. The sulfur-rich character of persulfurated coronene renders it a promising cathode material for lithium–sulfur batteries, displaying a high capacity of 520 mAh g–1 after 120 cycles at 0.6 C with a high-capacity retention of 90%

Renhao Dong

Image result for Renhao Dong DRESDEN

Research Group Leader

Renhao received his PhD in Physical Chemistry from Shandong University in 2013. Since 01/2017, he is a research group leader at the Chair for Molecular Functional Materials in TUD. His current research interest focuses on synthesis of organic 2D crystals (2D polymers/COFs/MOFs) and their applications in electronics and energy technology.

Contact

Phone: +49 – 351 / 463-40401 or -34932
Email: renhao.dong@tu-dresden.de

Prof. Xinliang Feng

Prof. Xinliang Feng

Work Biography:

This is a professorship in the context of the cluster of excellence cfaed.

Xinliang Feng received his Bachelor’s degree in analytic chemistry in 2001 and Master’s degree in organic chemistry in 2004. Then he joined Prof. Klaus Müllen’s group at the Max Planck Institute for Polymer Research for PhD thesis, where he obtained his PhD degree in April 2008. In December 2007 he was appointed as a group leader at the Max-Planck Institute for Polymer Research and in 2012 he became a distinguished group leader at the Max-Planck Institute for Polymer Research.

His current scientific interests include graphene, two-dimensional nanomaterials, organic conjugated materials, and carbon-rich molecules and materials for electronic and energy-related applications. He has published more than 370 research articles which have attracted more than 25000 citations with H-index of 75.

He has been awarded several prestigious prizes such as IUPAC Prize for Young Chemists (2009), Finalist of 3rd European Young Chemist Award, European Research Council (ERC) Starting Grant Award (2012), Journal of Materials Chemistry Lectureship Award (2013), ChemComm Emerging Investigator Lectureship (2014), Highly Cited Researcher (Thomson Reuters, 2014, 2015 and 2016), Fellow of the Royal Society of Chemistry (FRSC, 2014). He is an Advisory Board Member for Advanced Materials, Journal of Materials Chemistry A, ChemNanoMat, Energy Storage Materials, Small Methods and Chemistry -An Asian Journal. He is also one of the Deputy Leaders for European communitys pilot project Graphene Flagship, Head of ESF Young Research Group “Graphene Center Dresden”, and Working Package Leader of WP Functional Foams & Coatings of GRAPHENE FLAGSHIP.

Academic Employment

  • 12/2007-12/2012: Group Leader, Max Planck Institute for Polymer Research in Mainz, Germany
  • 06/2010: Director of the Institute of Advanced Organic Materials, Shanghai Jiao Tong University
  • 03/2011: Distinguished Adjunct Professorship in Shanghai Jiao Tong University, Chin
  • 12/2012-07/2014: Distinguished Group Leader, Max Planck Institute for Polymer Research in Mainz, Germany
  • 08/2014: W3 Chair Professor, Technische Universität Dresden, Germany

Honors and Duties

  • Marie Currie Fellowship (2005-2006)
  • Chinese Government Award for Outstanding Self-financed Students (2008)
  • IUPAC Prize for Young Chemists (2009)
  • Finalist of 3rd European Young Chemist Award (2010)
  • ISE (International Society of Electrochemistry) Young Investigator Award (2011)
  • Adjunct Professorship, China University of Geosciences (Wuhan) (2011)
  • Deputy Leader of one of the ten European representatives of the European community’s pilot project GRAPHENE FLAGSHIP (2012)
  • EU FET Young Explorer (2012)
  • ERC Starting Grant Award (2012)
  • Advisory Board Member for Advanced Materials (2013)
  • Journal of Materials Chemistry Lectureship Award (2013)
  • Advisory Board Member for Journal of Materials Chemistry A (2014)
  • Editorial Board Member of Chemistry – An Asian Journal (2014)
  • ChemComm Emerging Investigator Lectureship (2014)
  • Highly Cited Researcher (Thomson Reuters, 2014)
  • Fellow of the Royal Society of Chemistry (2014)
  • Highly Cited Researcher (Chemistry and Materials Science) (2015)
  • International Advisory Board of Energy Storage Materials (2015)
  • International Advisory Board of ChemNanoMat (2015)
  • Highly Cited Researcher (Chemistry and Materials Science, Thomson Reuters) (2016)
  • Head of ESF Young Research Group “Graphene Center Dresden” (2016)
  • Working Package Leader of WP Functional Foams & Coatings of GRAPHENE FLAGSHIP (2016)
  • International Advisory Board of Small Methods (2016)
  • Path Leader of 2.5D path within the cluster of excellence CFAED (2016)
  • ERC Proof-of-Concept Project Award (2017)
  • Small Young Innovator Award (2017)
  • Hamburg Science Award (2017)

Referee for:

Nature, Science, Nature Materials, Nature Nanotechnology, Nature Chemistry, Journal of the American Chemical Society, Angewandte Chemie International Edition, Nano Letters, Advanced Materials, Chemical Society Reviews, ACS Nano, Small, Chemical Communications, Chemistry of Materials, Organic Letters, Journal of the Organic Chemistry, Chemistry – A European Journal, ChemSusChem, ChemPhysChem, Macromolecular Rapid Communications, Journal of Material Chemistry, New Journal of Chemistry, Chemistry – An Asian Journal, ACS Applied Materials & Interfaces, Energy & Environmental Science, Organic Electronics and so on

Referee for research grants in NSF, US Department of Energy, ESF, ISF and Fondazione Cariparo and Fondazione CariModena.

Publications

Click to open publications list

Contact (Secretariat)

Phone: +49 351 / 463-43251
Fax: +49 351 / 463-43268
Email: sabine.strecker@tu-dresden.de

 

 

 

 

Klaus Müllen
Max-Planck-Institute for Polymer Research, Mainz, 55128, Germany
vyrez_DSC_3783.JPG

Research into energy technologies and electronic devices is strongly governed by the available materials. We introduce a synthetic route to graphenes which is based upon the cyclodehydrogenation (“graphitization”) of well-defined dendritic (3D) polyphenylene precursors. This approach is superior to physical methods of graphene formation such as chemical vapour deposition or exfoliation in terms of its (i) size and shape control, (ii) structural perfection, and (iii) processability (solution, melt, and even gas phase). The most convincing case is the synthesis of graphene nanoribbons under surface immobilization and in-situ control by scanning tunnelling microscopy.
Columnar superstructures assembled from these nanographene discs serve as charge transport channels in electronic devices. Field-effect transistors (FETs), solar cells, and sensors are described as examples.
Upon pyrolysis in confining geometries or “carbomesophases”, the above carbon-rich 2D- and 3D- macromolecules transform into unprecedented carbon materials and their carbon-metal nanocomposites. Exciting applications are shown for energy technologies such as battery cells and fuel cells. In the latter case, nitrogen-containing graphenes serve as catalysts for oxygen reduction whose efficiency is superior to that of platinum.

Müllen, K., Rabe, J.R., Acc. Chem. Res. 2008, 41, (4), 511-520;
Wang, X., Zhi, L., Müllen, K. Nano. Lett. 2008, 8, 323-327;
Feng, X.; Chandrasekhar, N.; Su, H. B.; Müllen, K., Nano. Lett. 2008, 8, 4259.;
Pang, S.; Tsao, H. N.; Feng, X.; Müllen, K., Adv. Mater. 2009, 31, 3488;
Feng, X., Marcon, V., Pisula, W., Hansen, M.R., Kirkpatrick, I., Müllen, K., Nature Mater. 2009, 8, 421;
Cai, J., Ruffieux, P., Jaafar, R., Bieri, M., Braun, T., Blankenburg, S., Muoth, M., Seitsonen, A. P., Saleh, M., Feng, X., Müllen, K., Fasel, R., Nature 2010, 466, 470-473;
Yang, S., Feng, X., Zhi, L., Cao, Q., Maier, J., Müllen, K., Adv. Mater. 2010, 22, 838; Liu, R., Wu, D., Feng, X., Müllen, K., Angew. Chem. Int. Ed. 2010, 49, 2565;
Käfer, D., Bashir, A., Dou, X., Witte, G., Müllen, K., Wöll, C., Adv. Mater. 2010, 22, 384;
Diez-Perez, I., Li, Z., Hihath, J., Li, J., Zhang, C., X., Zang, L., Dai, Y., Heng, X., Müllen, K., Tao, N. J. Nature Commun. 2010, DOI: 10.1038.

Prof. Dr. Klaus Müllen
joined the Max-Planck-Society in 1989 as one of the directors of the Max-Planck Institute for Polymer Research. He obtained a Diplom-Chemiker degree at the University of Cologne in 1969 after work with Professor E. Vogel. His Ph.D. degree was granted by the University of Basel, Switzerland, in 1972 where he undertook research with Professor F. Gerson on twisted pi-systems and EPR spectroscopic properties of the corresponding radical anions. In 1972 he joined the group of Professor J.F.M. Oth at the Swiss Federal Institute of Technology in Zürich where he worked in the field of dynamic NMR spectroscopy and electrochemistry. He received his habilitation from the ETH Zürich in 1977 and was appointed Privatdozent. In 1979 he became a Professor in the Department of Organic Chemistry, University of Cologne, and accepted an offer of a chair in Organic Chemistry at the University of Mainz in 1983. He received a call to the University of Göttingen in 1988.

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http://pubs.acs.org/doi/abs/10.1021/jacs.6b12630

https://cen.acs.org/articles/95/i49/molecules-of-the-year-2017.html?utm_source=Twitter&utm_medium=Social&utm_campaign=CEN&hootPostID=ea1deb5464b6231122901a3321f4ff5e

 

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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A derivatisation agent selection guide frequently applied in analytical chemistry and related disciplines.

 Uncategorized  Comments Off on A derivatisation agent selection guide frequently applied in analytical chemistry and related disciplines.
Dec 032017
 

 

A derivatisation agent selection guide

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC03108D, Paper
Open Access Open Access
Marek Tobiszewski, Jacek Namiesnik, Francisco Pena-Pereira
The study reported herein is aimed at the greenness assessment of 267 derivatisation agents that are frequently applied in analytical chemistry and related disciplines.

A derivatisation agent selection guide

 

Abstract

The study reported herein is aimed at the greenness assessment of 267 derivatisation agents that are frequently applied in analytical chemistry and related disciplines. Multicriteria decision analysis allowed obtaining three rankings of derivatisation agents applied in liquid chromatography, gas chromatography and chiral analysis. The criteria of assessment included the safety information obtained from material safety data sheets and physicochemical and environmental parameters predicted with relevant models. As for some of the agents predicted data were not available, these agents were assessed with a smaller number of criteria, within the ranking of low confidence. The results of the study will help to apply greener derivatisation agents, wherever the green chemistry principle of avoiding derivatisation cannot be fulfilled.

The present study provides an assessment, in terms of greenness, of 267 LC, GC and chiral derivatisation agents typically used in analytical chemistry and related fields. The preference rankings were performed for each group of derivatisation agents by means of MCDA according to the best relevant criteria that are available. In all three cases fine rankings were obtained for high and low confidence assumptions. For more informative assessment, it would be beneficial to include toxicological endpoints and more information about environmental persistence among assessment criteria. Incorporating valuable greenness indicators of synthesis processes such as carbon footprint or energy needs during production of each chemical as assessment criteria would be worthwhile. Unfortunately, these values are not easily available in the literature for a satisfactory number of derivatisation agents. Furthermore, recovery of derivatisation agents is another important issue that influences the greenness of derivatisation reactions, so its inclusion as assessment criterion would also be desirable. However, it is dependent on reaction specific conditions – not only the kind of derivatisation agent matters, but also analytes to be determined and solvents employed. The greenness of derivatisation agents is very rarely considered during analytical method development. The main criteria for selection of derivatisation agents are their rapidity and efficiency, but greenness should be also considered. This study allows selecting less problematic derivatisation agents for analytical method development while some clues can also be deduced for other than analytical applications.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC03108D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Image result for Gdańsk University of TechnologyImage result for Gdańsk University of Technology

 

Gdańsk University of Technology

Image result for Marek Tobiszewski gdansk

Marek Tobiszewski

.
.
Jacek Namieśnik at Gdansk University of Technology
Francisco Javier Pena-Pereira at University of Vigo

Research experience

  • Apr 2013–present
    Universidade de Vigo · Department of Analytical and Food Chemistry
    Spain · Vigo
  • Apr 2011–Mar 2013
    University of Aveiro · Centre for Environmental and Marine Studies (CESAM)
    Portugal · Aveiro
  • Jun 2005–Apr 2011
     Universidade de Vigo · Department of Analytical and Food Chemistry
    Spain · Vigo

 

Foto superior de la cabecera de 
				Universidade de Vigo
Foto del menú lateral Universidade de Vigo
Química

Faculty of Chemistry, University of Vigo

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Catalytic C-H amination at its limits: challenges and solutions

 organic chemistry, Uncategorized  Comments Off on Catalytic C-H amination at its limits: challenges and solutions
Nov 232017
 

 

Catalytic C-H amination at its limits: challenges and solutions

Org. Chem. Front., 2017, 4,2500-2521
DOI: 10.1039/C7QO00547D, Review Article
Damien Hazelard, Pierre-Antoine Nocquet, Philippe Compain
Pushing C-H amination to its limits fosters innovative synthetic solutions and offers a deeper understanding of the reaction mechanism and scope.

Catalytic C–H amination at its limits: challenges and solutions

 

Abstract

Catalytic C–H amination reactions enable direct functionalization of non-activated C(sp3)–H bonds with high levels of regio-, chemo- and stereoselectivity. As a powerful tool to unlock the potential of inert C–H bonds, C–H amination chemistry has been applied to the preparation of synthetically challenging targets since major simplification of synthetic sequences are expected from this approach. Pushing C–H amination to its limits has led to a deeper understanding of the reaction mechanism and scope. In this review, we present a description of the specific challenges facing catalytic C–H amination in the synthesis of natural products and related compounds, as well as innovative tactics created to overcome them. By identifying and discussing the major insights gained and strategies designed, we hope that this review will stimulate further progress in C–H amination chemistry and beyond.

Conclusion Since the seminal works of Du Bois in the early 2000s, the pace of discovery in the field of metal-catalysed C–H amination has been breath-taking. Not surprisingly, this synthetic tool has been applied to the total synthesis of many compounds of interest, given the high prevalence of the amino group in natural products and synthetic pharmaceuticals.67 Chemist’s confidence in the high potential of the C–H amination methodology to unlock inert C–H bonds has been demonstrated by its application to more and more challenging substrates. This has been a powerful drive for progress in the field. New valuable insights have been gained allowing, for example, a better regiochemical control via stereoelectronic and/or conformational effects. Innovative strategies have been discovered to direct the insertion event in substrates bearing a large degree of attendant functionality. Solutions have spanned from the elegant exploitation of kinetic isotope effects to the tactical use of protecting groups with different sizes or electronic characteristics. Systematic exploration of different catalytic systems has been also performed leading to the opening of new possibilities in C–H amination technology. Manganese-based catalysts have thus given rise to nitrenoids that overcome the low reactivity of primary aliphatic C–H bonds without interfering with weaker secondary/tertiary C–H bonds. Despite these impressive achievements, much remains to be done. Counterintuitive selectivity and unexplained reactivity should serve as a reminder that further studies are highly needed to understand in depth catalytic C–H amination chemistry. Many challenges remain on the way, from basic to applied research. A clear mechanistic view based on definitive evidence concerning the details of the C–N bond forming process would undoubtedly facilitate the rational design of efficient catalytic systems leading to higher regio-, chemio- and stereoselectivity. In particular, the quest for site-selective C–H amination through catalyst control has to be pursued.10d,e In this context, the development of efficient intermolecular C–H amination process still represents a major challenge and upcoming advancements are expected to increase the impact of this technology in organic synthesis. Future progress made in the field of catalytic C–H amination chemistry might also lead to industrial-scale applications in the next decade. It is likely that total synthesis of synthetically challenging targets related to natural products will continue to be a powerful driving force towards this goal.

STR1 STR2

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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Highly active, separable and recyclable bipyridine iridium catalysts for C–H borylation reactions

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Highly active, separable and recyclable bipyridine iridium catalysts for C–H borylation reactions
Nov 212017
 

Graphical abstract: Highly active, separable and recyclable bipyridine iridium catalysts for C–H borylation reactions

Highly active, separable and recyclable bipyridine iridium catalysts for C–H borylation reactions

Abstract

Iridium complexes generated from Ir(I) precursors and PIB oligomer functionalized bpy ligands efficiently catalyzed the reactions of arenes with bis(pinacolato)diboron under mild conditions to produce a variety of arylboronate compounds. The activity of this PIB bound homogeneous catalyst is similar to that of an original non-recyclable catalyst which allows it to be used under milder conditions than other reported recyclable catalysts. This oligomer-supported Ir catalyst was successfully recovered through biphasic extraction and reused for eight cycles without a loss of activity. Biphasic separation after the initial use of the catalyst led to an insignificant amount of iridium leaching from the catalyst to the product, and no iridium leaching from the catalyst was observed in the subsequent recycling runs. Arylboronate products obtained after extraction are sufficiently pure as observed by 1H and 13C-NMR spectroscopy that they do not require further purification.

Hind MAMLOUK, PhD

Hind MAMLOUK, PhD

R&D in Organic Materials Chemistry Looking for a New Challenge
Texas A&M University
3-Chloro-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)anisole (5). Transparent oil. Yield: 87%.
1H NMR (600 MHz, CDCl3) δ 7.37 (s, 1H), 7.22 – 7.16 (m, 1H), 6.99 (s, 1H), 3.82 (s, 3H), 1.34 (s, 12H);
13C NMR (101 MHz, CDCl3) δ 159.88, 134.57, 126.84, 117.71, 117.43, 84.15, 55.52, 24.82.
GCMS: RT=14.55 min, M+ = 268.1 vs MW= 268.54 g.mol-1 .
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Image result for Sherzod T. Madrahimov Texas A&M University at Qatar

Sherzod Madrahimov

Asst. Prof.

Research experience

  • Aug 2015–present
    Asst. Prof.
    Texas A&M University at Qatar · Chemistry
    Qatar · Doha
  • Jul 2012–Jul 2015
    PostDoc Position
    Northwestern University · Department of Chemistry
    United States · Evanston
  • Aug 2007–Jul 2012
    Graduate student
    University of Illinois, Urbana-Champaign · Department of Chemistry
    United States · Urbana

Image result for Texas A&M University at Qatar

Texas A&M University at Qatar

 

A headshot

David Bergbreiter
Professor

Contact

Department of Chemistry
Texas A&M University
College Station, TX 77843-3255

P: 979-845-3437
F: 979-845-4719
bergbreiter@chem.tamu.edu

Current Activities

Our group explores new chemistry related to catalysis and polymer functionalization using the tools and precepts of synthetic organic chemistry to prepare functional oligomers or polymers that in turn are used to either effect catalysis in a greener, more environmentally benign way or to more efficiently functionalize polymers. Often this involves creatively combining the physiochemical properties of a polymer with the reactivity of a low molecular weight compound to form new materials with new functions. These green chemistry projects involve undamental research both in synthesis and catalysis but has practical aspects because of its relevance to practical problems.

A common theme in our catalysis studies is exploring how soluble polymers can facilitate homogeneous catalysis. Homogeneous catalysts are ubiquitously used to prepare polymers, chemical intermediates, basic chemicals and pharmaceuticals. Such catalysts often use expensive or precious metals or expensive ligands or are used at relatively high catalyst loadings. The products often contain traces of these catalysts or ligands – traces that are undesirable for esthetic reasons or because of the potential toxicity of these impurities. Both the cost of these catalysts of these issues require catalyst/product separation – separations that often are inefficient and lead to chemical waste. These processes also use volatile organic solvents – solvents that have to be recovered and separated. Projects underway in our lab explore how soluble polymers can address each of these problems. Examples of past schemes that achieve this goal in a general way as highlighted in the Figure below.

We also use functional polymers to modify existing polymers. Ongoing projects involve molecular design of additives that can more efficiently modify polymers’ physical properties. We also use functional polymers in covalent layer-by-layer assembly to surface polymers’ surface chemistry. An example of this work is our use of ‘smart’ polymers that reversibly change from being water soluble cold to being insoluble and hydrophobic on heating. Such polymers’ have been used by us to prepare ‘smart’ catalysts, ‘smart’ surfaces and membranes, and to probe fundamental chemistry underlying temperature and salt-dependent protein solvation.

Jakkrit Suriboot

Jakkrit Suriboot

Research Assistant at Texas A&M University
Image result for Praveen Kumar Manyam TEXAS

Dr. Praveen Kumar

Title: Research Assistant Professor

Education: M.S., I.I.T. Roorkee
Ph.D., Panjab University Chandigarh (2008)
Visiting Fellow (w/ Prof. G. G. Balint-Kurti), Bristol University, UK
Postdoctoral Research Associate (w/ Prof. Svetlana Malinovskaya), Stevens Institute of Technology, Hoboken, NJ
Senior Postdoctoral Research Associate (w/ Prof. Seogjoo Jang), Queens College of CUNY, NY

Office: Chemistry 010

Phone: 806-742-3124

Email: praveen.kumar@ttu.edu

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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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Biovis PSA2000 Automated Particle Size Analysis System (The 21 CFR Part 11 compliance module )

 Uncategorized  Comments Off on Biovis PSA2000 Automated Particle Size Analysis System (The 21 CFR Part 11 compliance module )
Nov 122017
 

Inline images 1

Biovis PSA2000

Automated Particle Size Analysis System

Biovis PSA 2000 system designed to provide particle size and shape analysis with more than 70 measurements on size shape and color makes it a unique solution for R&D and QC applications in Pharmaceutical, Food processing, Paint , Ink Coating and many other applications. The 21 CFR Part 11 compliance module make it more preferred for the Manufacturing plants  working under USFDA guidelines. Report available on request, or download link available below, it  is as per the regulatory requirements.

For R&D the non FDA version of the software can provide huge amount of data which can be mined to help find more information about the particulate matter based on its size and shape thereby improve the Drug delivery, Process Engineering , process development etc…

Biovis PSA2000 is an automated particle size analysis system for comprehensive investigation of different types of dry or wet particulate matter such as fibres, emulsions, crystals, powders, spray droplets, or suspensions, etc.

– Rapid automated analysis of thousands of individual particles

– Detect particles as small as 0.5 micron

– Compliance to FDA 21 CFR Part 11 standards

– Custom built analysis routines to handle specific sample types

– Detect and classify particle types on the basis of size, shape, color

– Professional Analysis Report generation

 

The Biovis PSA 2000 system with Biovis Particle Plus Ver 5.3 has the following features

  • Reports with D10, D50, D90 values.
  • Number and Volume distribution charts
  • Administrator  driven Login Policies.
  • Powerful macros/methods for automatic detection of different types of samples to achieve repeatable results with different users for same samples.
  • Micro Image documentation with Electronic Signature as per 21 CFR Part II compliance guidelines.
  • Complete audit trail to trace every action in each experiment.

Departments that can benefit from Biovis PSA 2000 system are

  • Process development/ Process Engineering
  • Quality Control ( Finished Material/ Inward Raw Material)
  • Performance of finished product ( Aspect ratio /roundness factor helps better design of final product)
  • Research and Development

For more information please go through the weblink http://www.expertvisionlabs.com/BiovisPSA.html

Imaging Solutions

Bio-Science

BioScience application areas are turning out to be one of the leading consumers of digital imaging softwares. Quantitative analysis for images from microscopy is beneficial in Medical, Scientific and biological applications.
Image Analysis Software are used in the field of Pathology, MicroBiology, research & quality control of Medicine, Forensic sciences, etc.
Many of these fields require image processing techniques to enhance the Image before extracting relevant information from it. Characterization of minute details in the acquired image is essential in these scientific applications.

Biovis Image Plus

is perfectly suited for these applications and provides numerous functions for enhancement of Image and then obtaining morphometric, densitometry and stereological measurements.

Plant Sciences

The

Biovis PSM

– Plant Science Modules are a set of advanced solutions for a wide range of plant sciences applications. Biovis PSM is designed for Plant Pathology and Agronomy applications to provide solutions for Plant Leaf, Plant Root, Plant Seed analysis.
Whether for use in the lab, or for field level analysis, Biovis PSM is offered at different levels of flexibility and portability to the users.

Industrial Analysis

Industrial analysis requires a practical and efficient technique of studying metals and materials to understand their composition and behavior. Such Metallurgical analysis (metallography) by way of imaging softwares provides a fast and accurate method of estimating mechanical properties of materials based on their appearance. This helps to check and maintain that their product meets the required standard.
Microstructural image analysis is useful in Steel Industry, Metal Strength Analysis, manufacturing, automotive, quality control of materials, and for Metallurgist in material science applications.

Biovis Materials Plus

is aimed at providing solutions for these Material analysis requirements.

str10

Naveen Hegde

Regards

Naveen Hegde

Expert Vision Labs

H202, Ranjit Studio,

DP Road, Dadar East,

Mumbai 400014

India.

Tel:+91 22 6637 2739 / +91 22 6637 1470

Mobile: +91 93240 51848

Fax : +91 22 6637 2739

Website : www.expertvisionlabs.com

email : nhegde@expertvisionlabs.com

Expert Vision Labs

Expert Vision Labs has pioneered Image Analysis Technology in India and has focus into developing, a flexible line of highly cost effective and quality software driven products for Research and Industrial customers in India and across the globe.
Established in 1995, Expert Vision Labs has strived to specialize in providing complete solutions for computer based imaging and vision related applications. Have developed the

Biovis

image analysis product line for diverse applications in genetics, bioscience, material science and industrial applications.

Report available on request, or download  here is as per the regulatory requirements.
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“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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