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Thursday 28 December 2017

Sulfurative self-condensation of ketones and elemental sulfur: a three-component access to thiophenes catalyzed by aniline acid-base conjugate pairs


Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC03437G, Communication
Thanh Binh Nguyen, Pascal Retailleau
An aniline/acid-catalyzed method for constructing thiophenes 2 from inexpensive ketones 1 and elemental sulfur is reported.

Sulfurative self-condensation of ketones and elemental sulfur: a three-component access to thiophenes catalyzed by aniline acid–base conjugate pairs

 
Author affiliations

Abstract

A sulfurative self-condensation method for constructing thiophenes 2 by a reaction between ketones 1 and elemental sulfur is reported. This reaction, which is catalyzed by anilines and their salts with strong acids, starts from readily available and inexpensive materials, and releases only water as a by-product.
STR1

2,4-Di-p-tolylthiophene (2b)2
2 M. Arisawa, T. Ichikawa, and M. Yamaguchi, Chem. Commun. 2015, 51, 8821
STR1
Eluent heptane:toluene 9:1. 190 mg, 72%.
1 H NMR (300 MHz, CDCl3) δ 7.60-7.54 (m, 5H), 7.34 (s, 1H), 7.27-7.23 (m, 4H), 2.42 (s, 6H).
13C NMR (75 MHz, CDCl3) δ 145.3, 143.3, 137.8, 137.2, 133.5, 131.9, 129.9, 129.8, 126.5, 126.0, 122.1, 118.9, 21.5, 21.5.
STR1 STR2
STR1
Binh Thanh Nguyen at French National Centre for Scientific Research

Binh Thanh Nguyen

CV Binh Nguyen

CNRS Research Associate CR1 ( ORCID , ResearchGate )
ICSN-CNRS Bât. 27
1, avenue de la Terrasse
91190 Gif-sur-Yvette France
thanh-binh.nguyen_at_cnrs.fr
+33 1 69 82 45 49
- Education and work experience2015: Habilitation to Direct Research (HDR)
2011 - present: CNRS research associate at ICSN - Paris-Saclay University
2009 - 2011: Post-doctoral Fellow at ICSN (Dr. Françoise Guéritte and Dr. Qian Wang)
2003 - 2006: Ph.D. student at the UCO2M Organic Synthesis Laboratory (University of Maine, Le Mans, France, Dr. Gilles Dujardin, Dr. Arnaud Martel, Professor Robert Dhal)
- Research Interests
Green chemistry (Atom, step and redox economic transformation), green synthetic tools: O2, S8, photochemistry, iron catalyst
Elemental sulfur as a synthetic tool (building block, oxidant, reductant, catalyst)
Iron-sulfur catalysts
Heterocycle synthesis
- Scientific Communications
47 publications
- Selected recent publications ( complete list )
[1] Adv. Synth. Catal. 2017 , 359 , 1106.
[2] Asian J. Org. Chem. 2017 , 6 , 477.
[3] Org. Lett. 2016 , 18 , 2177.
[4] Org. Process Res. Dev. 2016 , 20 , 319.
[5] Angew. Chem. Int. Ed. 2014 , 53 , 13808.
[6] J. Am. Chem. Soc. 2013 , 135 , 118.
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Wednesday 27 December 2017

(2R,3S,4R,5R)-1-(3-((5-(4-Fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2,3,4,5,6-pentahydroxyhexan-1-one

Figure
CAS 1672658-93-3
C24 H25 F O6 S, 460.52
D-Glucopyranose, 1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-
 
 
str1
str1
CAS 1809403-04-0
C24 H25 F O6 S, 460.52
D-Glucose, 1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-
WO2017/93949
 
Figure
 
 
(2R,3S,4R,5R)-1-(3-((5-(4-Fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2,3,4,5,6-pentahydroxyhexan-1-one    12
From the FT-IR spectra of 12 contain a signal at 1674 cm–1, this signal is strongly indicative of a carbonyl ketone being present in 12
In 13C NMR and HMBC correlations spectra, the chemical shift at 199.75 ppm was observed. Analysis of the NMR data  confirmed that the structure of 12 is a ring-opened keto form
Synthesis of (2R,3S,4R,5R)-1-(3-((5-(4-Fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2,3,4,5,6-pentahydroxyhexan-1-one 12
title compound 12 (84.23% yield) and having 99.4% purity by HPLC;
 
DSC: 160.84–166.44 °C;
 
Mass: m/z 459 (M+–H);
 
IR (KBr, cm–1): 3313, 2982, 1674.7, 1601, 1507.5, 1232.7;
 
1H NMR (600 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.80 (dd, J = 1.8 Hz, 1H), 7.61–7.58 (m, 2H), 7.33 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 3.6 Hz, 1H), 7.21–7.18 (m, 2H), 6.84 (d, J = 3.6 Hz, 1H), 5.17 (dd, J = 3.6, 3.0 Hz, 1H), 5.02 (d, J = 6.6 Hz, 1H), 4.57 (d, J = 4.8 Hz, 1H), 4.43–4.39 (m, 3H), 4.22 (s, 2H), 4.02–4.01 (m, 1H), 3.53–3.51 (m, 3H), 3.38–3.37 (m, 1H), 2.35 (s, 3H);
 
13C NMR (101 MHz, DMSO-d6) δ 199.7, 162.6, 160.2, 142.8, 142.1, 140.5, 138.8, 133.3, 130.5, 130.4, 130.4, 129.3, 127.2, 127.0, 127.0, 126.7, 123.5, 116.0, 115.8, 75.2, 72.3, 71.8, 71.3, 63.2, 33.2, 19.2.
 
HRMS (ESI): calcd m/zfor [C24H25FO6S + Na]+ = 483.1248, found m/z 483.1244.
 
 
 
 
 
 
 
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.7b00281
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Wednesday 20 December 2017

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

 

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC02862H, Paper
Peter Olsen, Michael Oschmann, Eric V. Johnston, Bjorn Akermark
Ring opening of cyclic carbonates with unprotected amino acids in water - a route to highly functional carbamates.

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

 
 Author affiliations

Abstract

The present work shows that it is possible to ring-open cyclic carbonates with unprotected amino acids in water. Fine tuning of the reaction parameters made it possible to suppress the degree of hydrolysis in relation to aminolysis. This enabled the synthesis of functionally dense carbamates containing alkenes, carboxylic acids, alcohols and thiols after short reaction times at room temperature. When Glycine was used as the nucleophile in the ring-opening with four different five membered cyclic carbonates, containing a plethora of functional groups, the corresponding carbamates could be obtained in excellent yields (>90%) without the need for any further purification. Furthermore, the orthogonality of the transformation was explored through ring-opening of divinylenecarbonate with unprotected amino acids equipped with nucleophilic side chains, such as serine and cysteine. In these cases the reaction selectively produced the desired carbamate, in 70 and 50% yield respectively. The synthetic design provides an inexpensive and scalable protocol towards highly functionalized building blocks that are envisioned to find applications in both the small and macromolecular arena.
link  http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC02862H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract
STR1 STR2
 
 
Image result for Peter Olsén stockholm
Affiliation
Stockholm University
Location
  • Stockholm, Sweden
Position
  • PostDoc Position

Research experience

  • Jun 2010–Feb 2016
    PhD Student
    KTH Royal Institute of Technology · Department of Fibre and Polymer Technology
    Sweden · Stockholm
Stockholms universitet hem
 
 
 
 
Image result for Björn Åkermark stockholm

Education

  • Jan 1962–Jun 1967
    KTH Royal Institute of Technology
    Organic Chemistry and Catalysis · PhD
    Sweden · Stockholm

Awards & achievements

  • Jun 2009
     
    Award: Bror Holmberg Medal, Swedish Chemical Society
  • Feb 2009
     
    Award: Ulla and Stig Holmquists Prize, Uppsala University
  • Oct 1997
     
    Award: Dr hc, University D´Aix-Marseille
  • Oct 1991
     
    Award: KTH Prize for Excellence in Teaching
  • Oct 1978
     
    Award: Arrhenius Medal, Swedish Chemical Society
  • Aug 1977
     
    Scholarship: Zorn Fellowship, Swden America Foundation
  • Nov 1976
     
    Award: Letterstedt Award, Roy Swed. Acad. of Science
 
6.jpg
 
 

Dr. Eric Johnston, Ph.D.

Sigrid Therapeutics
Chief Technology Officer
Dr. Eric V. Johnston obtained his Master of Science degree in 2008 at the Department of Organic Chemistry, Stockholm University, Sweden. In the same year, he started his graduate studies under the supervision of Prof. Jan-Erling Bäckvall. During his PhD, he worked on the development of new homogeneous and heterogeneous transition-metal catalysts.
After receiving his PhD in 2012, he joined Prof. Samuel J. Danishefskys research group at Memorial Sloan-Kettering Cancer Center, New York, USA as a postdoctoral fellow supported by The Swedish Research Council. Here he was engaged in the total chemical synthesis of glycolsylated proteins that play important roles in modern cancer treatment.
In 2014 he returned to the Department of Organic Chemistry at Stockholm University to establish his own group. The goal of his research is to contribute new advances to the strategy and methodology for the preparation of synthetic macromolecules such as proteins, glycopeptides, sequence and length-controlled polymers. He is also a Co-Supervisor for Prof. Björn Åkermarks research group, which aims at studying and developing new homogeneous, as well as heterogeneous, water oxidation catalysts.
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Tuesday 19 December 2017

Benzyl (5-methylpyrazin-2-yl)carbamate

2-(Cbz-Amino)-5-methylpyrazine.png

2-(Cbz-Amino)-5-methylpyrazine

Molecular Formula:C13H13N3O2
Molecular Weight:243.266 g/mol
 
 
str1
Benzyl (5-methylpyrazin-2-yl)carbamate
CAS 1033418-57-3
Mp 191.4 °C.
IR 1719, 1567, 1353, 1226, 1054, 759, 744, 706 cm–1.
1H NMR (DMSO-d6, 500 MHz) 10.45 (br, 1H), 8.93 (s, 1H), 8.20 (s, 1H), 7.42–7.32 (m, 5H), 5.18 (s, 2H), 2.41 (s, 3H).
13C NMR (DMSO-d6, 125.7 MHz) 153.6, 147.7, 146.7, 141.7, 136.5, 134.3, 128.7 (2C), 128.4, 128.2 (2C), 66.5, 20.4.
HRMS elemental calculated for C13H14N3O2 (MH+): 244.1086; found: 244.1080.

NMR PREDICT
1H NMR
13 C NMR PREDICT
Use of a Curtius Rearrangement as Part of the Multikilogram Manufacture of a Pyrazine Building Block
 Pharmaceutical Technology & Development, AstraZeneca, Charter Way, Macclesfield, SK10 2NA, United Kingdom
 Cyton Biosciences Ltd., 68 Macrae Road, Bristol, BS20 0DD, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.7b00340
 
 
 
MORE...............
 

A modular flow reactor for performing Curtius rearrangements as a continuous flow process

Abstract

The use of a mesofluidic flow reactor is described for performing Curtius rearrangement reactions of carboxylic acids in the presence of diphenylphosphoryl azide and trapping of the intermediate isocyanates with various nucleophiles.
Graphical abstract: A modular flow reactor for performing Curtius rearrangements as a continuous flow process
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O=C(OCc1ccccc1)Nc2cnc(C)cn2

Monday 11 December 2017

Hypericin



Structural formula of hypericin
Hypericin
Hypericin is a naphthodianthrone, an anthraquinone derivative which, together with hyperforin, is one of the principal active constituents of Hypericum (Saint John's wort).[2][3] Hypericin is believed to act as an antibiotic, antiviral[2] and non-specific kinaseinhibitor. Hypericin may inhibit the action of the enzyme dopamine β-hydroxylase, leading to increased dopamine levels, although thus possibly decreasing norepinephrine and epinephrine.
It was initially believed that the anti-depressant pharmacological activity of hypericin was due to inhibition of monoamine oxidase enzyme. The crude extract of Hypericum is a weak inhibitor of MAO-A and MAO-B. Isolated hypericin does not display this activity, but does have some affinity for NMDA receptors.[citation needed] This points in the direction that other constituents are responsible for the MAOI effect. The current belief is that the mechanism of antidepressant activity is due to the inhibition of reuptake of certain neurotransmitters.[2]
The large chromophore system in the molecule means that it can cause photosensitivity when ingested beyond threshold amounts.[citation needed] Photosensitivity is often seen in animals that have been allowed to graze on St. John's Wort. Because hypericin accumulates preferentially in cancerous tissues, it is also used as an indicator of cancerous cells. In addition, hypericin is under research as an agent in photodynamic therapy, whereby a biochemical is absorbed by an organism to be later activated with spectrum-specific light from specialized lamps or laser sources, for therapeutic purposes. The antibacterial and antiviral effects of hypericin are also believed to arise from its ability for photo-oxidation of cells and viral particles.[2]
Hypericin derives from polyketides cyclisation.[4][5]
The biosynthesis of hypericins is in the polyketide pathway where an octaketide chain goes through processes of cylizations and decarboxylations form emodin anthrone which are believed to be the precursors of hypericin. Oxidization reactions yield protoforms which then are converted into hypericin and pseudohypericin. These reactions are photosensitive and take place under exposure to light and using the enzyme Hyp-1. [6][7][8][9][10]

References

  1. Jump up^ Merck Index, 11th Edition, 4799
  2. Jump up to:a b c d Mehta, Sweety (2012-12-18). "Pharmacognosy of St. John's Wort". Pharmaxchange.info. Retrieved 2014-02-16.
  3. Jump up^ Oubre, Alondra (1991). "Hypericin: the active ingredient in Saint John's Wort". Archived from the original on September 28, 2007. Retrieved September 18, 2006.
  4. Jump up^ Loren W. Walker (1999). "A Review of the Hypothetical Biogenesis and Regulation of Hypericin synthesis via the Polyketide Pathway in Hypericum perforatum and Experimental Methods Proposed to Evaluate the Hypothesis".
  5. Jump up^ Christian Hertweck (2009). "Polyketide Biosynthesis". Angew. Chem. Int. Ed48: 4688–4716. doi:10.1002/anie.200806121.
  6. Jump up^ Karioti A, Bilia AR (2010) Hypericins as potential leads for new therapeutics. Int J Mol Sci 11:562-594
  7. Jump up^ Falk H (1999) From the photosensitizer hypericin to the photoreceptorstentorian—the chemistry of phenanthroperylene quinines. AngewChem Int Ed 38:3116–3136
  8. Jump up^ Bais HP, Vepachedu R, Lawrence CB, Stermitz FR, Vivanco JM (2003)Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John’s wort(Hypericum perforatum L.). J Biol Chem 278:32413–32422
  9. Jump up^ Michalska K, Fernades H, Sikorski M, Jaskolski M (2010) Crystal structure of Hyp-1, a St. John’s wort protein implicated in the biosynthesis of hypericin. J Struct Biol 169:161–171
  10. Jump up^ Murthy, Hosakatte Niranjana et al. “Hypericins: Biotechnological Production from Cell and Organ Cultures.” Applied Microbiology and Biotechnology 98.22 (2014): 9187–9198. PubMed. Web.
str1 str2 str3

An Efficient Multigram Synthesis of Hypericin Improved by a Low Power LED Based Photoreactor

 Department of Chemistry, State University of Maringá, Avenue Colombo, 5790, Maringá, Paraná 87020-900, Brazil
Instituto Federal de Educação, Ciência e Tecnologia Catarinense, 283, Concórdia, Santa Catarina 89703-720, Brazil
§ Department of Pharmacy, State University of Maringá, Avenue Colombo, 5790, Maringá, Paraná 87020-900, Brazil
Federal University of Parana, Jandaia do Sul, Paraná 86900-000, Brazil
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.7b00317
 
Image result for Renato S. Gonçalves Maringá
Location
  • Maringá, Brazil
Position
  • Professor
Universidade Estadual de Maringá

Abstract

Abstract Image
In this work, an improved synthesis process was developed for the multigram production of hypericin. An inexpensive and efficient low power Light Emission Diode (LED) based photoreactor was designed and employed to perform the protohypericin photocyclization reaction allowing its photoconversion in hypericin. This closed system overcomes safety issues related to scale-up hypericin preparation typically described in the literature which combines the use of open systems, organic solvents, and high-power light sources. The photoreactor designed allows a solution to, mainly, the intrinsic effect of hypericin photobleaching inherent to the protohypericin photocyclization reaction, implying an increase in the yield of the final product and consequently the final cost. Using a red-LED based photoreactor, a safety protocol was carried out in a 5-g scale hypericin preparation with quantitative yield.
C30H16O8;
1H NMR (CD3CN, 25 °C, 500 MHz): δH 14.75 (s, 2H, OH-1, OH-6), 14.13 (s, 2H, OH-7, OH-12), 7.31 (s, 2H, Ar-H8, Ar-H11), 6.55 (s, 2H, Ar-H2, Ar-H5), 2.71 (s, 6H, Ar-CH3) ppm; UV–vis (EtOH) λmax 392, 480, 513, 552, 596.
13C NMR (CD3CN, 25 °C, 500 MHz): δC 185.2, 175.7, 169.8, 162.8, 144.6, 128.4, 127.6, 122.7, 122.1, 120.5, 119.6, 109.9, 106.6, 103.5.
The identification of molecular formula of Hypericin (C30H16O8) was confirmed on its negative HRMS ion of m/z 503.0854 (calcd for [M – H] 503.0845). The MS2 experiment showed fragment ions characteristic for this compound of m/z 487.0202 [M–H–CH4], 458.0504 [M–H–CO2–H·], 433.0361 [M–H–CH2═C═O–CO], 431.0601 [M–H–CO2–CO], and 405.0425 [M–H–CH2═C═O–2CO].
The characterization data of hypericin are in agreement with the literature.(35-39)
  • 35.
    KapinusE. I.FalkH.TranH. T. N. Monatsh. Chem. 1999130623– 635 DOI: 10.1007/s007060050222
  • 36.
    PiperopoulosG.LotzR.WixforthA.SchmiererT.ZellerK.-P. J. Chromatogr., Biomed. Appl. 1997695309– 316 DOI: 10.1016/S0378-4347(97)00188-6
  • 37.
    BrolisM.GabettaB.FuzzatiN.PaceR.PanzeriF.PeterlongoF. J. Chromatogr. A 19988259– 16 DOI: 10.1016/S0021-9673(98)00697-9
  • 38.
    RiedelK.-D.RiegerK.Martin-FacklamM.MikusG.HaefeliW. E.BurhenneJ. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2004,81327– 33 DOI: 10.1016/j.jchromb.2004.09.061
Hypericin[1]
Structural formula of hypericin
Ball-and-stick model of the hypericin molecule
Names
1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione
Other names
4,5,7,4',5',7'-Hexahydroxy-2,2'-dimethylnaphthodianthrone
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard100.008.129
PubChem CID
UNII
Properties
Chemical formulaC30H16O8
Molar mass504.45 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
/////////////Hypericin