DR ZOE WILSON

Post Doctoral Research Associate in the group of Professor Steven V. Ley working on the synthesis of complex natural products and synthetic methodology.

2a

(4S,5S)-5-Methyl-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid methyl ester (2a).

The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditionsSteffen Glöckner, Duc N. Tran, Richard J. Ingham, Sabine Fenner, Zoe E. Wilson, Claudio Battilocchio and Steven V. Ley DOI: 10.1039/C4OB02105C, Paper From themed collection Recent Advances in Flow Synthesis and Continuous Processing

The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions

Steffen Glöckner,a   Duc N. Tran,a   Richard J. Ingham,a  Sabine Fenner,a   Zoe E. Wilson,a   Claudio Battilocchioa and  Steven V. Ley*a

*Corresponding authors

aDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK

E-mail: svl1000@cam.ac.uk Web: http://www.leygroup.ch.cam.ac.uk/

Org. Biomol. Chem., 2015,13, 207-214

DOI: 10.1039/C4OB02105C

A rapid flow synthesis of oxazolines and their oxidation to the corresponding oxazoles is reported. The oxazolines are prepared at room temperature in a stereospecific manner, with inversion of stereochemistry, from β-hydroxy amides using Deoxo-Fluor®. The corresponding oxazoles can then be obtained via a packed reactor containing commercial manganese dioxide

	Fig. 1 Oxazoline- and oxazole-containing natural products.

	Scheme 1 Optimised conditions for the flow synthesis of oxazolines.

	Scheme 2 Microchip reaction for the preparation of oxazolines.

	Scheme 3 Platform set up for the scale up experiment.

	Scheme 4 Flow oxidation of aryl-oxazolines using activated MnO2.

	Scheme 5 Flow oxidation of 2-alkyl-oxazolines using amorphous MnO2. aDeprotection was observed.

	Scheme 6 Automated oxidation of oxazolines using a Raspberry Pi® computer and a multiple position valve.

Table 1 Flow cyclodehydration of β-hydroxy amides using Deoxo-Fluor®

Entrya	Substrate		Product		Isolated yieldb
a Reactions were run on a 2 mmol scale. b Compounds were isolated without purification. c The crude material was passed through a plug of calcium carbonate/silica in place of an aqueous work up. d Total flow rate = 10 mL min−1 with 2.6 eq. of Deoxo-Fluor®.
1		1a		2a	98%
2		1b		2b	98%
3		1c		2c	79%c
4		1d		2d	98%
5		1e		2e	99%
6		1f		2f	95%
7		1g		2g	98%
8		1h		2h	92%
9		1i		2i	95%
10		1j		2j	60%
11		1k		2k	85%d
12		1l		2l	92%d

………………………………………   

  2a

(4S,5S)-5-Methyl-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid methyl ester (2a).

General protocol for the preparation of oxazoline in flow

A solution of Deoxo-Fluor® (1 mL, 50% in toluene) in CH2Cl2 (7.0 mL) and a solution of β-hydroxy amide (2 mmol) in CH2Cl2 (8 mL) were combined at a T-piece (each stream run at 3.0 mL min−1) and reacted at rt in a 10 mL PFA reactor coil. The combined stream was then directed to an aqueous quenching stream (9 mL min−1) and the solution directed to a liquid/liquid separator.22

(4S,5S)-5-Methyl-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid methyl ester (2a).

2a

 1H-NMR (600 MHz, CDCl3) δ = 7.98–7.96 (m, 2H), 7.49–7.46 (m, 1H), 7.40–7.38 (m, 2H), 5.05 (dq, 1H, J= 10.2, 6.4 Hz), 4.97 (d, 1H, J = 10.2 Hz), 3.76 (s, 3H), 1.37 (d, 3H, J = 6.5 Hz); 

13C-NMR (151 MHz, CDCl3) δ = 170.5, 166.2, 131.9, 128.6, 128.4, 127.3, 77.7, 71.8, 52.2, 16.3; 

HR-MS (ESI+) for C12H14NO3+ [M + H]+ calc.: 220.0974, found: 220.0981; 

FT-IR neat,  (cm−1) = 2953, 1736, 1645, 1603, 1580, 1496, 1450, 1384, 1349, 1244, 1197, 1174, 1067, 1045, 1001, 973, 934, 904, 886, 851, 778, 695; 

specific rotation: [α]24.1D = +58.58° cm3 g−1 dm−1 (c = 8.5 in ethanol). Lit.: [α]20D = +69.4° cm3 g−1 dm−1 (c = 8.5 in EtOH).39

39…………H. Aït-Haddou, O. Hoarau, D. Cramailére, F. Pezet, J.-C. Daran and G. G. A. Balavoine, Chem. – Eur. J., 2004, 10, 699–707

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Dr Zoe Wilson

Post Doctoral Research Associate in the group of Professor Steven V. Ley working on the synthesis of complex natural products and synthetic methodology.

College Lecturer and Fellow at Murray Edwards College.

Research Group

Ley Group Website

Telephone number

01223 336698 (shared)

Email address

zw261@cam.ac.uk

College

Murray Edwards College

Email: zw261@cam.ac.uk    LinkedIn Profile

Zoe grew up on a farm in the small town of Warkworth, New Zealand. After completing her studies she moved to Auckland, New Zealand to attend the University of Auckland where she completed a Bachelor of Science in Medicinal Chemistry then a BSc (Hons) in Medicinal Chemistry under the supervision of Professor Margaret Brimble, working on the synthesis of anti-Helicobacter pylori compounds. She was then funded by a University of Auckland scholarship to carry out Ph.D. research with Professor Brimble into the synthesis of the extremophile natural product berkelic acid. Upon completion of her Ph.D. she was awarded a Newton International Fellowship from the Royal Society to move to the United Kingdom and join the research group of Professor Steven V. Ley in the Department of Chemistry, University of Cambridge. Upon completion of the two year Newton Fellowship, she was then employed as a Post-Doctoral Research Associate to continue working in the Ley group. While in Cambridge, she has been working on the total synthesis of the complex natural products azadirachtin and plantazolicins A and B, in the process developing novel chemistry. In October 2013 Zoe was appointed as a College Lecturer and Fellow at Murray Edwards College.

Teaching

Graduate Lecture Series – Reduction in Organic Chemistry (2 lectures) (2014, 2013)

Senior demonstrator Chemistry II laboratories (2014/2015)

Senior demonstrator Chemistry IB laboratories (2012/2013, 2013/2014)

College Lecturer at Murray Edwards College

Publications

12.          Zoe E. Wilson, Sabine Fenner and Steven V. Ley, “Total syntheses of linear poly-thiazole/oxazole plantazolicin A and its biosynthetic precursor plantazolicin B”, Angew. Chem. Int. Ed., 2015, 54, 1284 – 1288 DOI: 10.1002/anie.201410063R1

11.          Steffen Glöckner, Duc N. Tran, Richard J. Ingham, Sabine Fenner, Zoe E. Wilson, Claudio Battilocchio and Steven V. Ley, “The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions”, Org. Biomol. Chem.,2015, 13, 207–214, DOI: 10.1039/c4ob02105c

10.          Michael C. McLeod, Zoe E. Wilson and Margaret A. Brimble, “Formal synthesis of berkelic acid: a lesson in α-alkylation chemistry”, J. Org. Chem., 2012, 77, 1, 400–416, DOI: 10.1021/jo201988m

9.            Michael C. McLeod, Margaret A. Brimble, Dominea C. K. Rathwell, Zoe E. Wilsonand Tsz-Ying Yuen, “Synthetic approaches to [5,6]-benzannulated spiroketal natural products”, Pure Appl. Chem., 2012, 84, 6, 1379-1390, DOI: 10.1351/PAC-CON-11-08-06

8.            Michael C. McLeod, Zoe E. Wilson and Margaret A. Brimble, “An enantioselective formal synthesis of berkelic acid”, Org. Lett., 2011, 13, 19, 5382 – 5385, DOI: 10.1021/ol202265g

7.            Zoe E. Wilson, Jonathan G. Hubert, Margaret A. Brimble, “A flexible approach to 6,5-benzannulated spiroketals”, Eur. J. Org. Chem., 2011, 3938-3945, DOI: 10.1002/ejoc.201100345

6.            Jonathan Sperry, Yen-Cheng (William) Liu, Zoe E. Wilson, Jonathan G. Hubert, Margaret A. Brimble, “Synthesis of benzannulated spiroketals using an oxidative radical cyclization”, Synthesis, 2011, 9, 1383-1398, DOI: 10.1055/s-003001259981

5.            Jonathan Sperry, Zoe E. Wilson, Dominea C. K. Rathwell and Margaret A. Brimble, “Isolation, biological activity and synthesis of benzannulated spiroketal natural products”, Nat. Prod. Rep., 2010, 27, 1117-1137, DOI: 10.1039/b911514p

4.            Zoe E. Wilson and Margaret A. Brimble, “A flexible asymmetric synthesis of the tetracyclic core of berkelic acid using a novel Horner-Wadsworth-Emmons/oxa-Michael cascade”, Org. Biomol. Chem., 2010, 8, 1284-1286, DOI: 10.1039/B927219B

3.            Zoe E. Wilson and Margaret A. Brimble, “Molecules derived from the extremes of life”, Nat. Prod. Rep., 2009, 26, 44–71, DOI: 10.1039/b800164m

Featured as an Instant insight article in Chemical Biology (“Life at the extremes”,Chemical Biology, 2008, 3, B95) and featured on the cover of the issue (Nat. Prod. Rep.,2009, 26, 1-2, DOI: 10.1039/B821737H)

2.            Fiona J. Radcliff, John D. Fraser, Zoe E. Wilson, Amanda M. Heapy, James E. Robinson, Christina J. Bryant, Christopher L. Flowers, and Margaret A. Brimble, “Anti-Helicobacter pylori activity of derivatives of the phthalide-containing antibacterial agents spirolaxine methyl ether, CJ-12,954, CJ-13,013, CJ-13,102, CJ-13,104, CJ-13,108 and CJ-13,015”, Bioorg. Med. Chem., 2008, 16, 6179–6185, DOI: 10.1016/j.bmc.2008.04.037

1.            Zoe E. Wilson, Amanda M. Heapy and Margaret A. Brimble, “Synthesis of indole analogues of the anti-Helicobacter pylori compounds CJ-13,015, CJ-13,102, CJ-13,104 and CJ-13,108”, Tetrahedron, 2007, 63, 5379–5385, DOI: 10.1016/j.tet.2007.04.067

Take a tour

Trobriand Island

Trobriand Islands - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Trobriand_Islands

The Trobriand Islands are a 450 km² archipelago of coral atolls off the eastern coast of New Guinea. They are part of the nation of Papua New Guinea and are ...

‎Geography - ‎People - ‎History - ‎Anthropological studies and ...

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Traditional: Trobriand Islanders wear red grass skirts unique to the islands for ceremonies and weddings. Completing the look are traditional feathered headbands

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He was followed in the 1930s by a Catholic Mission but the islanders, although ruled by first the British and then the Australians, clung firm to their traditional ways.

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Chief's family: The house of the chieftain is recognisable by its height, shell decorations and the presence of a malagan - a carved, painted totem pole

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Changing times: Although some modern items such as musical instruments have been embraced, islanders cling to many traditions, including keeping pigs as pets

Is that a googly? Cricket is hugely popular and was introduced by colonial authorities. Banned from going to war, the islanders settle their differences with a game

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Magic: Although many, among them seven-year-old Salome, go to school, the Trobriand Islanders continue to believe in magic and believe it is responsible for conception

Important: Because yams are a sign of wealth, yam houses - huts where the tubers are stored - are very important. Those belonging to chiefs are highly decorated

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Delicate: Teenage girls wear tortoiseshell earrings which they eventually pass on to their daughters, while traditional kula boats come covered in cowrie shells

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Jewellery: Most of the Trobriand Islanders sport elaborate bracelets and necklaces, all of which are made from natural materials such as shells, stones and feathers

Rare: Because the islands are coral atolls, anything made from stone is considered rare and valuable. This stone was polished and given as a wedding gift

Excitement: The weekly flight from Port Moresby, capital of Papua New Guinea, is the most exciting moment of the week for many and draws huge crowds

War: During World War II, thousands of American soldiers were stationed on the Trobriand Islands. Vintage dog tags can be picked up for as little as 20p

Remote: The idyllic islands are home to the Trobriand Islanders, who still live in much the same way as they always have - including fishing from wooden canoes

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Flow Synthesis of Fluorinated α-Amino Acids

Dr. Susan Wilkinson, Deputy Editor for the European Journal of Organic Chemistry, talks to Professor Beate Koksch, Freie Universität Berlin, Germany, and Professor Peter Seeberger, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, about their article on the synthesis of fluorinated amino acids recently published in the European Journal of Organic Chemistry.

Flow Synthesis of Fluorinated α-Amino Acids

Dr. Wilkinson, European Journal of Organic Chemistry, talks to Professors Koksch and Seeberger about fluorinated amino acids
Read more
http://www.chemistryviews.org/details/ezine/7956531/Flow_Synthesis_of_Fluorinated_-Amino_Acids.html
 Professor Beate Koksch, Freie Universität Berlin, Germany,
.Prof. Dr. Beate Koksch
Institute of Chemistry and Biochemistry – Organic Chemistry 
Freie Universität Berlin 
Takustr. 3
14195 Berlin
Working Group: AG Koksch
Space: 32.18
Tel .: + 49-30-838-55344, Fax -55 644
Secretariat:
Tel .: + 49-30-838-55880
(woman Skowronski, room 32.17)
Email: Beate.Koksch fu-berlin.de

.

++49 – 30 – 838 55344  e-mail  homepage (http://userpage.chemie.fu-berlin.de/~akkoksch/) Free University of Berlin Takustr. 3 14195 Berlin Germany

Nominated by

• German Research Foundation (DFG)
• AcademiaNet member since 13.03.2015

Employed by

• Freie Universität Berlin

Academic Discipline/Fields

• Natural sciences/ Engineering/ Agricultural sciences

Field

Chemistry

Area of specialisation

Organic and Natural Product Chemistry

Research interests

• folding mechanisms occuring in neurodegenerative diseases
• developing new multivalent scaffolds
• investigating the impact of fluorine on amino acids, peptides and proteins

Distinctions and Awards

• Georg Thieme publisher’s award, 2002Lessing medal in gold, 1986

………………………………………………..
Professor Peter Seeberger, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany

Since 2011, Professor Peter H. Seeberger, Max Planck Institute of Colloids and Interfaces in Potsdam, Germany, is Editor-in-Chief of the Beilstein Journal of Organic Chemistry.
Editor-in-Chief of the Beilstein Journal of Organic Chemistry is Professor Peter H. Seeberger, Max Planck Institute of Colloids and Interfaces in Potsdam, Germany, who is supported by a distinguished board of associate editors, each of whom is responsible for a particular subject area within the journal’s scope. Over 40 scientists from all over the world, including several Nobel Prize laureates, support the Beilstein Journal of Organic Chemistry as Advisory Board members.
Prof. Dr. Peter H. Seeberger

Director

Phone:+49 30 838-59301Fax:+49 30 838-59302

Email:boehme@…

German researchers develop cheap and high-yield process to manufacture anti-malaria drug

Jan 18, 2012

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam and the Freie Universität Berlin have developed a very simple process for the synthesis of artemisinin – the best anti-malaria drug – more economically and in sufficient volumes for all patients. This means that it will be possible to provide medication for the 225 million malaria patients in developing countries at an affordable price.
An Anopheles female mosquito that transmits malaria(© picture alliance/dpa Fotografia)Over one million people die of malaria each year because they do not have access to effective drugs.Millions, especially in the developing world, cannot afford the combination drug preparation, which consists mainly of artemisinin.
Moreover, the price for the medication varies, as this substance is isolated from sweet wormwood (Artemisia annua) which grows mainly in China and Vietnam, and varies seasonally in its availability.
Pharmaceutical companies could only obtain the drug from plants up to now. The chemists use a waste product from current artemisinin production as their starting substance. This substance can also be produced biotechnologically in yeast, which the scientists convert into the active ingredient using a simple yet very ingenious method.
This may be about to change. Peter H. Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin and his colleague François Lévesque have discovered a very simple way of synthesising the artemisinin molecule, which is known as an anti-malaria drug from traditional Chinese medicine and has an extremely complex chemical structure. “The production of the drug is therefore no longer dependent on obtaining the active ingredient from plants,” says Peter Seeberger.
Synthesis from a by-product of artemisinin production
As a starting point, the chemists use artemisinic acid – a substance produced as a hitherto unused by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes ten times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a much simpler structure. “We convert the artemisinic acid into artemisinin in a single step,” says Peter Seeberger. “And we have developed a simple apparatus for this process, which enables the production of large volumes of the substance under very controlled conditions.”
The effect of the molecule, which not only targets malaria but possibly also other infections and even breast cancer, is due to, among other things, a very reactive chemical group formed by two neighbouring oxygen atoms – which chemists refer to as an endoperoxide. Peter Seeberger and François Lévesque use photochemistry to incorporate this structural element into the artemisinic acid. Ultraviolet light converts oxygen into a form that can react with molecules to form peroxides.
800 photoreactors should suffice to cover the global requirement for artemisinin
Dr. Peter H. Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin(© dpa)“Photochemistry is a simple and cost-effective method. However, the pharmaceutical industry has not used it to date because it was so difficult to control and implement on a large scale,” explains Peter Seeberger.
“The fact that we do not carry out the synthesis as a one-pot reaction in a single vessel, but in a continuous-flow reactor enables us to define the reaction conditions down to the last detail,” explains Peter Seeberger.
After just four and a half minutes a solution flows out of the tube, in which 40 percent of the artemisinic acid has become artemisinin. “We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin,” says Peter Seeberger. And it could all happen very quickly. Peter Seeberger estimates that the innovative synthesis process could be ready for technical use in a matter of six months. This would alleviate the global shortage of artemisinin and exert considerable downward pressure on the price of the associated drugs…….see        http://www.india.diplo.de/Vertretung/indien/en/__pr/Edu__Science__News/Malaria__drug.html

Max Planck Institute for Colloids and Interfaces

Peter Seeberger
Department of Biomolecular Systems
Max Plank Institute for Colloids and Interfaces
(Potsdam, Germany)
peter.seeberger@mpikg.mpg.de
http://www.peter-seeberger.de/
The core interests our research program currently address the following areas:
Automated oligosaccharide synthesis

• Rapid access to monosaccharide by de-novo synthesis
• New protecting groups
• New Glycosylating Agents
• New linkers for solid phase carbohydrate synthesis
• Assembly of complex structures (in particular N-Glycans, O-Glycans)
• Optimization of steps followingthe assembly, like deprotection, modification and conjugation

Total Synthesis of Biologically Important Oligosaccharides

• Tumor-associated antigens
• HIV-related oligosaccharides
• Bacterial cell-surface antigens
• N-linked glycoproteins

Chemical Synthesis and Biochemistry of Proteoglycans

• Modular synthesis of heparin/heparan sulfates
• Creation of heparin microarray
• Optimization of the building blocks synthesis
• Study of the SAR (structure-activity relationship) and the interactions between Proteoglycans and proteins
• Automated synthesis of heparin fragments

Total Synthesis and Biological Activity of Glycosylphosphatidylinositols (GPIs)

• Total syntheses of GPIs
• Development of a synthetic GPI malarial vaccine
• Elucidation of the biosynthesis of GPI
• Immunological response to synthetic GPIs

Development of Cabohydrate-based Vaccines

• A fully synthetic malaria vaccine
• Leishmania vaccine
• Synthetic HIV vaccine
• Synthetic TB vaccine

Microreactors for Organic Synthesis

• (Automated) Synthesis in continuous flow Microreactors
• Photochemistry in Microflow reactors
• Catalysis in Microreactors

Carbohydrate Microarrays
De novo synthesis
Nanoparticules and Colloidal Polymers

• Quantum dots
• Supramolecular dendrimers
• Emulsion polymerization of nanoparticules

http://www.theguardian.com/technology/2012/feb/05/malaria-drug-synthesis-peter-seeberger
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take a tour
Potsdam, Germany

1. Potsdam – Wikipedia, the free encyclopedia

   en.wikipedia.org/wiki/Potsdam

   Potsdam (German pronunciation: [ˈpɔtsdam] ( listen)), is the capital city of the German federal state of Brandenburg. It directly borders the German capital Berlin  …
   

   ‎Potsdam Conference - ‎Sanssouci - ‎City Palace, Potsdam - ‎New Palace

 

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