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

Uncategorized Comments Off

Jan 232018

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

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

Angela F. Ku^a and Gregory D. Cuny*^a

Author affiliations

*Corresponding authors

^aDepartment of Pharmacological and Pharmaceutical Sciences, University of Houston, Science and Research Building 2, Houston, USA
E-mail: gdcuny@central.uh.edu

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.

(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

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

Angela F. Ku† and Gregory D. Cuny^*‡

^†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., 2015, 17 (5), pp 1134–1137

DOI: 10.1021/acs.orglett.5b00007

*E-mail: gdcuny@central.uh.edu.

Abstract

7-Oxygenated aporphines 1–6 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 1–5 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,

Utilization of fluoroform for difluoromethylation in continuous flow: a concise synthesis of α-difluoromethyl-amino acids

FLOW CHEMISTRY, flow synthesis Comments Off

Jan 162018

Utilization of fluoroform for difluoromethylation in continuous flow: a concise synthesis of [small alpha]-difluoromethyl-amino acids

Green Chem., 2018, 20,108-112
DOI: 10.1039/C7GC02913F, Communication

Open Access

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Manuel Kockinger, Tanja Ciaglia, Michael Bersier, Paul Hanselmann, Bernhard Gutmann, C. Oliver Kappe
Difluoromethylated esters, malonates and amino acids (including the drug eflornithine) are obtained by a gas-liquid continuous flow protocol employing the abundant waste product fluoroform as an atom-efficient reagent.

Utilization of fluoroform for difluoromethylation in continuous flow: a concise synthesis of α-difluoromethyl-amino acids

Manuel Köckinger,^a Tanja Ciaglia,^a Michael Bersier,^b Paul Hanselmann,^b Bernhard Gutmann*^a^c and C. Oliver Kappe*^a^c

Author affiliations

* Corresponding authors

^a Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria
E-mail: bernhard.gutmann@uni-graz.at, oliver.kappe@uni-graz.at

^b Microreactor Technology, Lonza AG, CH-3930 Visp, Switzerland

^c Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria

Abstract

Fluoroform (CHF₃) can be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethylation protocol on sp³ carbons employing fluoroform as a reagent. The protocol is applicable for the direct C^α-difluoromethylation of protected α-amino acids, and enables a highly atom efficient synthesis of the active pharmaceutical ingredient eflornithine.

Methyl 3,3-(difluoro)-2,2-diphenylpropanoate (2a) The product mixtures were collected and the solvent removed in vacuo. The products were isolated by thin layer chromatography (dichloromethane/hexane = 3/2 (v/v)). Yield: 173 mg (0.62 mmol, 62%); 93% by 19F NMR ;light yellow viscous liquid. 1 H NMR (300 MHz, D2O): δ = 7.45 – 7.19 (m, 10H), 6.90 (t, 2 JHF = 55.0 Hz, 1H), 3.79 (s, 3H). 13C NMR (75 MHz, D2O): δ = 171.1, 136.3, 129.8, 128.3, 128.2, 115.6 (t, 1 JCF = 246.2 Hz), 64.7, 53.1.19F NMR (282 MHz, D2O):δ = -123.0 (d, 2 JHF = 55.0 Hz).

Conclusions

A gas–liquid continuous flow difluoromethylation protocol employing fluoroform as a reagent was reported. Fluoroform, a by-product of Teflon manufacture with little current synthetic value, is the most attractive reagent for difluoromethylation reactions. The continuous flow process allows this reaction to be performed within reaction times of 20 min with 2 equiv. of base and 3 equiv. of fluoroform. Importantly, the protocol allows the direct C^α-difluoromethylation of protected α-amino acids. These compounds are highly selective and potent inhibitors of pyridoxal phosphate-dependent decarboxylases. The starting materials are conveniently derived from the commercially available α-amino acid methyl esters, and the final products are obtained in excellent purities and yields after simple hydrolysis and precipitation. The developed process appears to be especially appealing for industrial applications, where atom economy, sustainability, reagent cost and reagent availability are important factors.

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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

Jan 122018

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

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

Evaldas Klumbys,^a Ziga Zebec,^a Nicholas J. Weise,^a Nicholas J. Turner^a and Nigel S. Scrutton*^a

* Corresponding authors

^a Manchester Institute of Biotechnology (MIB), School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, UK
E-mail:nigel.scrutton@manchester.ac.uk

Evaldas Klumbys

Image result for Nigel Scrutton

Prof Nigel ScruttonScD, FRSC, FRSB

Professor of Enzymology and Biophysical Chemistry

Email:
Nigel.Scrutton@manchester.ac.uk

Phone: +44 (0) 161 306 5152

Full contact details

ORCID: 0000-0002-4182-3500

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.

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

Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides

organic chemistry, spectroscopy, SYNTHESIS Comments Off

Dec 292017

Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC02627G, Paper

Kathiravan Murugesan, Thirusangumurugan Senthamarai, Manzar Sohail, Muhammad Sharif, Narayana V. Kalevaru, Rajenahally V. Jagadeesh
Nanoscale Fe₂O₃-catalyzed environmentally benign synthesis of nitriles and amides has been performed from easily accessible aldehydes and ammonia using O₂.

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC02627G?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Stable and reusable nanoscale Fe₂O₃-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides

Kathiravan Murugesan,^a Thirusangumurugan Senthamarai,^a Manzar Sohail,^b Muhammad Sharif,^b Narayana V. Kalevaru^a and Rajenahally V. Jagadeesh*^a

Author affiliations

* Corresponding authors

^a Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
E-mail:Jagadeesh.Rajenahally@catalysis.de

^b The Center of Research Excellence in Nanotechnology (CENT) and Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

Abstract

The sustainable introduction of nitrogen moieties in the form of nitrile or amide groups in functionalized molecules is of fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report the nanoscale iron oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in the presence of 1 bar O₂ or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds to synthesise functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Additionally, applying this iron-based protocol, primary amides have also been prepared in a water medium.

1H NMR (300 MHz, Chloroform-d) δ 7.17 – 6.96 (m, 2H), 6.93 – 6.70 (m, 1H), 4.33 – 4.11 (m, 4H). 13C NMR (75 MHz, Chloroform-d) δ 147.75 , 143.80 , 125.87 , 121.21 , 118.91 , 118.25 , 104.38 , 64.59 , 64.12 . Off white solid

cas 19102-07-9

1,4-Benzodioxan-6-carbonitrile (8CI)
2,3-Dihydro-1,4-benzodioxin-6-carbonitrile
1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)nitrile

Melting Point, °C
105 – 106 Tetrahedron, 2015, vol. 71, 29, p. 4883 – 4887

Melting Point, °C

105 – 106

Tetrahedron, 2015, vol. 71, 29, p. 4883 – 4887

NMR PREDICTS

1H NMR

13C NMR PREDICT

More…………….

Journal of the American Chemical Society, 2001, vol. 123, 49, p. 12202 – 12206

More………….

RSC Advances, 2013, vol. 3, 44, p. 22389 – 22396

http://www.rsc.org/suppdata/ra/c3/c3ra44386h/c3ra44386h.pdf

MORE……..

Organic Letters, 2017, vol. 19, 12, p. 3095 – 3098

http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.7b01199/suppl_file/ol7b01199_si_001.pdf

2,3-Dihydrobenzo[b][1,4]dioxine-6-carbonitrile (Scheme 1, 2n) According to the general procedure A, the reaction of 1n (0.20 mmol), zinc cyanide (2.0 equiv), PCyPh2 (0.20 equiv) and Pd(OAc)2 (0.05 equiv) in dioxane (0.25 M) for 16 h at 150 °C, afforded after work-up and chromatography the title compound in 75% yield (24.2 mg). White solid. 1H NMR (500 MHz, CDCl3) δ 7.17-7.11 (m, 2H), 6.91 (d, J = 8.1 Hz, 1H), 4.32-4.31 (m, 2H), 4.30- 4.26 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 147.84, 143.91, 126.04, 121.37, 119.01, 118.37, 104.62, 64.71, 64.24.

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

green chemistry, organic chemistry, PROCESS, spectroscopy, SYNTHESIS Comments Off

Dec 282017

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

Thanh Binh Nguyen*^a and Pascal Retailleau^a

Author affiliations

* Corresponding authors

^a Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1, av de la Terrasse, 91198 Gif-sur-Yvette, France
E-mail: nguyen@icsn.cnrs-gif.fr

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.

2,4-Di-p-tolylthiophene (2b)2

2 M. Arisawa, T. Ichikawa, and M. Yamaguchi, Chem. Commun. 2015, 51, 8821

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.

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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Ultrasonic Assisted Extraction of Artemisinin from Artemisia Annua L. Using Monoether based Solvents

PROCESS Comments Off

Dec 252017

Artemisia Annua L

Ultrasonic Assisted Extraction of Artemisinin from Artemisia Annua L. Using Monoether based Solvents

Yongqiang Zhang, Phongphat Prawang, CHUNSHAN LI, Xiangzhan Meng, Yu Zhao, Hui Wang and Suojiang Zhang

Abstract

Artemisinin is a kind of natural antimalarial drug exhibiting low toxicity with a very fast action against malaria. Solvent extraction is the most widely used method to separate artemisinin from the Chinese medicinal herb Artemisia annua L. In this study, a series of monoether based solvents have been proposed to extract artemisinin and propylene glycol methyl ether (PGME) was found to be the most appropriate one for this extraction. Ultrasonic irradiation was demonstrated to be able to assist artemisinin extraction. Influences of extraction conditions, including liquid/solid ratio, extraction temperature, ultrasonic time, ultrasonic power, on the extraction efficiency were discussed by single factor experiments, and the main influence factors were optimized by responds surface method. The extraction mechanism was explored with spectroscopic characterizations, and kinetics of this process was also studied. Results indicate that ultrasonic assisted extraction using PGME has faster extraction rate than conventional solvents, and ultrasonic can significantly enhance mass transfer. Compared with conventional extraction, the process developed here exhibited higher efficiency (13.79 mg/g vs. 13.29 mg/g) and short extraction time (decreased from 8 h to 0.5 h) at a relatively low temperature. In addition, PGME has low toxicity and volatility, making the extraction process more safe and reliable. Therefore, this proposed method demonstrates that PGME based ultrasonic assisted extraction is a rapid, efficient, simple and safe technique for natural product extraction.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC03191B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

/////////// Artemisinin, Artemisia Annua L, extraction

HMF in multicomponent reactions: utilization of 5-hydroxymethylfurfural (HMF) in the Biginelli reaction

organic chemistry, spectroscopy, SYNTHESIS Comments Off

Dec 212017

HMF in multicomponent reactions: utilization of 5-hydroxymethylfurfural (HMF) in the Biginelli reaction

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC03425C, Paper

Weigang Fan, Yves Queneau, Florence Popowycz
The use of the renewable platform molecule 5-hydroxymethylfurfural (HMF) in the multi-component Biginelli reaction has been investigated.

HMF in multicomponent reactions: utilization of 5-hydroxymethylfurfural (HMF) in the Biginelli reaction

Weigang Fan,^a Yves Queneau*^a and Florence Popowycz*^a

http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC03425C?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

* Corresponding authors

^a Université de Lyon, INSA Lyon, ICBMS, Equipe Chimie Organique et Bioorganique, UMR 5246 CNRS, Université Lyon 1, CPE Lyon, Bâtiment Jules Verne, 20 Avenue Albert Einstein, F-69621 Villeurbanne Cedex, France
E-mail: yves.queneau@insa-lyon.fr, florence.popowycz@insa-lyon.fr

Abstract

The use of the renewable platform molecule 5-hydroxymethylfurfural (HMF) in the multi-component Biginelli reaction has been investigated. Multicomponent reactions (MCR) using HMF offer straightforward access to novel fine chemicals. However, the peculiar reactivity and lower stability of HMF have limited its use in such strategies. In this paper, we report our results on the use of HMF in 3-component Biginelli reactions, leading in one single step to a series of functionalized dihydropyrimidinones obtained in moderate to good yields, with a broad substrate scope of 1,3-dicarbonyl compounds and urea building blocks. This is the first report on the use of HMF in this reaction. The CH₂OH motif found in HMF provides useful functionalization for the target molecules, which cannot be offered by simpler aldehydes such as furfural.

5-Acetyl-4-[5’-(hydroxymethyl)furan-2’-yl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4a):

Reaction time: 8 h; Global yield: 86%; (78% yield after simple filtration + additional 8% yield after purification of the filtrate by column chromatography).

1H NMR (400 MHz, DMSO-d6) δ 9.22 (d, 1H, J = 1.2 Hz, H1), 7.88 (dd, 1H, J = 3.4, 1.2 Hz, H3), 6.16 (d, 1H, J = 3.1 Hz, H4’), 6.03 (d, 1H, J = 3.1 Hz, H3’), 5.27 (d, 1H, J = 3.4 Hz, H4), 5.18 (t, 1H, J = 5.6 Hz, OH), 4.33 (d, 2H, J = 5.6 Hz, CH2), 2.25 (s, 3H, CH3-C6), 2.17 (s, 3H, CH3CO).

13C NMR (100 MHz, DMSO-d6) δ 193.9 (COCH3), 155.1, 154.9 (C2’, C5’), 152.4 (C2), 149.0 (C6), 107.7 (C4’), 107.1 (C5), 106.3 (C3’), 55.7 (CH2OH), 47.9 (C4), 30.0 (CH3CO), 19.0 (CH3-C6).

HRMS (ESI) m/z: Calcd for [M+Na]+ C12H14N2NaO4 273.0846; Found 273.0850.

Weigang Fan

Research experience

Sep 2015–Mar 2017

Doctorant

Institut National des Sciences Appliquées de Lyon · Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires (ICBMS – UMR 5246)

France · Lyon

Florence POPOWYCZ

Université de Lyon, INSA Lyon, ICBMS, Equipe Chimie Organique et Bioorganique, UMR 5246 CNRS, Université Lyon 1, CPE Lyon, Bâtiment Jules Verne, 20 Avenue Albert Einstein, F-69621 Villeurbanne Cedex, France
E-mail: florence.popowycz@insa-lyon.fr

Yves QUENEAU

CNRS Research Director chez ICBMS INSA Lyon Univ Lyon – Carbohydrate Chemistry

ICBMS INSA Lyon University of Lyon

///////////////HMF, multicomponent reactions, 5-hydroxymethylfurfural, Biginelli reaction

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

organic chemistry, spectroscopy, SYNTHESIS Comments Off

Dec 202017

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected [small alpha]-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

Peter Olsén,*^a Michael Oschmann,^a Eric V. Johnston*^a and Björn Åkermark*^a

Author affiliations

*Corresponding authors

^aDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE 106 91, Stockholm, Sweden
E-mail: peter.olsen@su.se, eric@sigridthx.com, bjorn.akermark@su.se

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

Affiliation

Stockholm University

Location

Stockholm, Sweden

Department

Department of Organic Chemistry

Position

PostDoc Position

Research experience

Jun 2010–Feb 2016

PhD Student

KTH Royal Institute of Technology · Department of Fibre and Polymer Technology

Sweden · Stockholm

Björn Åkermark

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

Dr. Eric Johnston, Ph.D.

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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Applications and perspectives of nanomaterials in novel vaccine development

nanotechnology, VACCINE Comments Off

Dec 112017

Applications and perspectives of nanomaterials in novel vaccine development

Med. Chem. Commun., 2018, Advance Article
DOI: 10.1039/C7MD00158D, Review Article

Yingbin Shen, Tianyao Hao, Shiyi Ou, Churan Hu, Long Chen
Vaccines show great potential for both prophylactic and therapeutic use in infections, cancer, and other diseases

Applications and perspectives of nanomaterials in novel vaccine development

http://pubs.rsc.org/en/Content/ArticleLanding/2018/MD/C7MD00158D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FMD+%28RSC+-+Med.+Chem.+Commun.+latest+articles%29#!divAbstract

Yingbin Shen,^a Tianyao Hao,^a Shiyi Ou,^a Churan Hu^a and Long Chen*^a

* Corresponding authors

^a Department of Food Science and Engineering, School of Science and Engineering, Jinan University, Guangzhou 510632, China
E-mail: shenybin412@gmail.com, daisyhallaiesec@gmail.com, tosy@jnu.edu.cn, hucr622@gmail.com, dexterchen@jnu.edu.cn
Fax: +86 020 852 26630
Tel: +86 138 801 32918

Abstract

Vaccines show great potential for both prophylactic and therapeutic use in infections, cancer, and other diseases. With the rapid development of bio-technologies and materials sciences, nanomaterials are playing essential roles in novel vaccine formulations and can boost antigen effectiveness by operating as delivery systems to enhance antigen processing and/or as immune-potentiating adjuvants to induce or potentiate immune responses. The effect of nanoparticles in vaccinology showed enhanced antigen stability and immunogenicity as well as targeted delivery and slow release. However, obstacles remain due to the lack of fundamental knowledge on the detailed molecular working mechanism and in vivo bio-effects of nanoparticles. This review provides a broad overview of the current improvements in nanoparticles in vaccinology. Modern nanoparticle vaccines are classified by the nanoparticles’ action based on either delivery system or immune potentiator approaches. The mechanisms of interaction of nanoparticles with the antigens and the immune system are discussed. Nanoparticle vaccines approved for use are also listed. A fundamental understanding of the in vivo bio-distribution and the fate of nanoparticles will accelerate the rational design of new nanoparticles comprising vaccines in the future.

Image result for Department of Food Science and Engineering, School of Science and Engineering, Jinan University

Department of Food Science and Engineering, School of Science and Engineering, Jinan University

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A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

spectroscopy, SYNTHESIS Comments Off

Dec 082017

A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

Green Chem., 2017, 19,5703-5707
DOI: 10.1039/C7GC02097J, Paper

Domenico C. M. Albanese, Nicoletta Gaggero, Meng Fei
Hexafluoro-2-propanol as the solvent allows a catalyst free domino approach to 2,3-dihydro-1,5-benzothiazepines in up to 98% yield.

A practical synthesis of 2,3-dihydro-1,5-benzothiazepines

Domenico C. M. Albanese,^a Nicoletta Gaggero*^b and Meng Fei^b

*Corresponding authors

^aDepartment of Chemistry, Università degli Studi di Milano, via C. Golgi 19, Milano, Italy

^bDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, via L. Mangiagalli 25, Milano, Italy
E-mail:nicoletta.gaggero@unimi.it

Domenico C. M. Albanese

University of Milan

LocationMilano, Italy

DepartmentDepartment of Chemistry

Positionassociate professor

Domenico Albanese received his Ph.D. degree in 1993 with Prof. Dario Landini working on phase transfer catalysis. After short stays at Imperial College London and the Technical University of Denmark, he gained a permanent position at the Università degli Studi di Milano, where he was appointed associate professor in 2008. His research interests include novel developments of phase-transfer catalysis, green chemistry and the development of new environmentally friendly antifouling agents.

University of Milan

image file: c4ra11206g-p2.tif

Nicoletta Gaggero

Nicoletta Gaggero received her Ph.D. degree in 1992 working on stereoselective reactions with natural proteins, enzymes and models of enzymes. After working at the Laboratoire de Chimie de Coordination du CNRS of Toulouse, she obtained a permanent position at the Università degli Studi di Milano. Her research interests cover the field of biocatalysis and asymmetric synthesis.

Abstract

2,3-Dihydro-1,5-benzothiazepines have been obtained through a domino process involving a Michael addition of 2-aminothiophenols to chalcones, followed by in situ cyclization. Up to 98% chemical yields have been obtained at room temperature under essentially neutral conditions by using hexafluoro-2-propanol as an efficient medium.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC02097J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

2,4-Diphenyl-2,3-dihydro-1,5-benzothiazepine (4a)

Yellow solid; mp 114-116 C [lit.1 , 114-115 °C], AcOEt/PE 1:9. 1H NMR (300 MHz, CDCl3,): 3.07 (t, J = 12.6 Hz, 1 H), 3.32 (dd, J = 4.7, 13.1 Hz, 1 H), 4.99 (dd, J = 4.5, 12.0 Hz, 1 H), 7.12-7.17 (m, 1 H), 7.25-7.30 (m, 5 H), 7.44-7.51 (m, 4 H), 7.62 (d, J = 6.1 Hz, 2 H), 8.06 (d, J = 7.5 Hz, 2 H). Isolated Yield: 339 mg, 86%.

2-(4-Hydroxyphenyl)-4-phenyl-2,3-dihydro-1,5-benzothiazepine (4e)

Light brown solid; mp 131-134 °C. AcOEt/PE 40:60.

1H NMR (CDCl3, 300 MHz):  = 3.01 (t, J = 12.7 Hz, 1 H), 3.28 (dd, J = 4.8, 12.9 Hz, 1 H), 4.95 (dd, J = 4.7, 12.5 Hz, 1 H), 5.10 (bs, 1 H), 6.76 (d, J = 8.5 Hz, 2 H), 7.18-7.21 (m, 3 H), 7.35 (d, J = 8.5 Hz, 1 H), 7.46- 7.55 (m, 4 H), 7.63 (dd, J =1.5, 7.7 Hz, 1 H), 8.06 (m, 2 H).

13C NMR (CDCl3, 75 MHz): 37.99 (CH2), 60.07 (CH), 115.53 (CH), 123.08 (C), 127.40 (CH), 128.79 (CH), 131.17 (CH), 136.54 (C), 141.59 (C), 155.24 (C). IR (KBr): 1599, 2921, 3350 cm-1 .

MS (ESI): m/z= 332.24 (MH)+ .

Anal. Calcd. for C21H17NOS: C, 76.10; H, 5.17; N, 4.23, found: C, 76.21; H, 5.15; N, 4.24.

Isolated Yield: 360 mg, 87%.