Author Archive

Organic & Biomolecular Chemistry welcomes new Associate Editor Huan Wang

We are delighted to welcome our new Associate Editor, Professor Huan Wang to the Organic & Biomolecular Chemistry Editorial Board!

Professor Wang graduated from Peking University (2005). He obtained his PhD from University of Maryland at College Park (2010), and conducted post-doctoral research work at University of Illinois at Urbana-Champaign (2010-2014). Wang started at Nanjing University in 2014 and works as a Professor in the Chemistry department.

His research group aims to address problems at the interface of chemistry and biochemistry, including the chemical synthesis and biosynthesis of bioactive peptides, peptide/protein functionalisation and biological functions of non-coding RNAs.

Find out more about Huan on his website and submit your article to him today!

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Call For Papers: Chemoenzymatic Synthesis

Call For Papers: Chemoenzymatic Synthesis

Guest edited by Hiroki Oguri, Hongzhi Cao & Suvarn Kulkarni

We are delighted to announce a call for papers for our latest online themed collection in Organic & Biomolecular Chemistry on Chemoenzymatic Synthesis guest edited by Professor Hiroki Oguri (University of Tokyo, Japan), Professor Hongzhi Cao (Ocean University of China, China) and Professor Suvarn Kulkarni (IIT Bombay, India).

This collection in OBC is dedicated to the emerging advancements in Chemoenzymatic Synthesis across a wide array of natural products, including sugars, lipids, terpenes, polyketides, peptide, alkaloids and their hybrids. This integrative synthetic approach not only harnesses the power of enzymes but also leverages the versatility of chemical synthesis regarding substrate design and product diversification.

This call for papers is open to both communication (for urgent work – up to 5 pages) and full papers.

 

Open for submissions until 30th April 2024

 

If you would like to contribute to this themed collection, you can submit your article directly through the OBC online submission service. Please mention that this submission is a contribution to the Chemoenzymatic Synthesis collection in the “Themed issues” section of the submission form and add a “Note to the Editor” that this is from the Open Call. The Editorial Office reserves the right to check suitability of submissions in relation to the scope of both the journal and the collection, and inclusion of accepted articles in the final themed issue is not guaranteed.

Please also note that all submissions will be subject to our usual rigorous peer review process, including initial assessment to ensure the high standards of the journal and acceptance is not guaranteed. Accepted manuscripts will be highlighted together in a dedicated virtual collection alongside an editorial, regardless of submission date, and there will be no delay in the publication of all accepted manuscripts into regular issues of OBC.

If you have any questions about the collection, then please contact the Editorial Office at obc-rsc@rsc.org and they will be happy to help.

With best regards,

Hiroki, Hongzhi and Suvarn

Professor Hiroki Oguri (University of Tokyo, Japan)

Professor Hongzhi Cao (Ocean University of China, China)

Professor Suvarn Kulkarni (IIT Bombay, India)

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20th Anniversary Blog Series: Peter Langer

2023 marks twenty of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from Professor Peter Langer at the University of Rostock who first published with OBC in 2008 and he has continued to support the journal with 47 articles across the years, most recently earlier this year.

About Peter

Peter was born in Hannover, Germany in 1969. From 1989 till 1994, he studied chemistry at the University of Hannover. His diploma thesis he carried out at the Massachusetts Institute of Technology (Cambridge, USA). Between 1994 and 1997, Peter did his PhD studies at the University of Hannover. Afterwards, he spent one year in Cambridge, UK to work as a postdoc. From 1998 till 2001, he carried out his research towards habilitation of the University of Göttingen, Germany. In 2002, Peter was appointed full professor (C4) at the University of Greifswald and later in 2004, full professor (C4) at the University of Rostock where he is working as the head of the chair of organic chemistry. Peter is also affiliated to the Leibniz-Institute of Catalysis e. V. at the University of Rostock (LIKAT). He has coauthored about 800 research papers and reviews, nearly 50 of them in OBC and supervised about 100 PhD students from various countries, 100 MSc and 50 BSc students. His students come from all over the world. Besides German and English, Peter speaks French, Spanish and Russian.

His research is focused on the development of new reactions and heterocyclic molecules and their application in the field of medicine and materials science. Peter has received several awards and scholarships; he was scholar of the German Academic Scholarship Foundation, of the Chemical Industry Fund, and of the Alexander von-Humboldt foundation. In addition, he obtained a Heisenberg scholarship of the German Research Foundation (DFG). Peter has received 10 honorary doctorates, 3 honorary professorships and several medals and research awards. He is an elected member of the Academy of Sciences of the Republic of Armenia and of the Academy of Sciences of the Islamic Republic of Pakistan. In addition, he was decorated with the civil award ‘Sitara-i-Quaid-i-Azam’ given by the President of Pakistan.

First OBC paper: S. Reim, D. Michalik, K. Weisz, Z. Xiao & P. Langer, Synthesis and Solution Structure of 3,5-Dioxopimelic Acid Diesters – Stable 1,3,5,7-Tetracarbonyl Derivatives, Org. Biomol. Chem., 2008, 6, 3079-3084, DOI: 10.1039/b805808c

Most recent OBC paper: E. Ammon, P. Heine, M. A. A. Cordero, S. Lochbrunner, A. Villinger, P. Ehlers & P. Langer, Dibenzoacridines: Synthesis by Alkyne-Carbonyl-Metathesis and Properties, Org. Biomol. Chem., 2023, 21, 4504-4517, DOI: 10.1039/d3ob00407d

Favourite OBC paper: T. N. Ngo, P. Ehlers, T. T. Dang, A. Villinger & P. Langer, Synthesis of indolo[1,2-f]phenanthridines by Pd-catalyzed domino C–N coupling/hydroamination/C–H arylation reactions, Org. Biomol. Chem., 2015, 13, 3321-3330, DOI: 10.1039/c5ob00013k

 

How has your research developed over the last 20 years?

During an academic career in Germany, at least for my generation, it was a requirement to change the field of research when you move from dependent (PhD, postdoc) to independent research (habilitation, junior or assistant professorship). In fact, during my career, I worked in various fields of research. My diploma thesis (equivalent to a Master thesis) I did in the group of Dietmar Seyferth at Massachusetts Institute of Technology in the field of organosilicon chemistry. My doctoral degree under the supervision of H. Martin R. Hoffmann at the University of Hannover I obtained in the field of natural products, specifically Cinchona alkaloids and my postdoc with Steven V. Ley at Cambridge University I did in carbohydrate chemistry. In 1998, I started my independent career habilitation under the mentorship of Armin de Meijere at the University of Göttingen. At that time the field of bioorganic chemistry was rather new and modern. But I had no idea of this field, was a bit afraid and decided to stay with organic synthesis for my independent research.

During my habilitation, I developed cyclization reactions of free and masked dianions. The latter are electroneutral equivalents of dianions, for example 1,3-bis(silyloxy)-1,3-butadienes. This work turned out to be fruitful and importantly rather inexpensive and I continued in the area during my tenure as full professor first at the University of Greifswald and since 2004, at the University of Rostock. After having published many, maybe too many, articles in the field, we moved more and more away from it. It soon became clear it was better to start something new and it was more and more difficult to publish in high ranked journals. As a consequence, in 2006, we started to work in the field of transition metal catalysis and developed new regioselective Pd catalysed coupling reactions of a great variety of polyhalogenated heterocyclic substrates such as pentachloropyridine or tetrabromothiophene. Later, starting in 2012, we began to investigate the combination of such coupling reactions with cyclizations by twofold Buchwald-Hartwig reactions, domino C-C coupling / hydroamination reactions, cycloisomerizations and CH-activations. In this context, we became also more and more interested in the synthesis of new heterocyclic core structures and their optical, electrochemical and electronic properties and started to carry out extensive fluorescence and cyclovoltammetric studies and also started to apply computational work to complement our experimental investigations. This nowadays represents about 80% of the research in my group.

A more recent field in my group is the application of alkyne-carbonyl metathesis (ACM) reactions to new heterocyclic substrates. Starting in 2010, we started three new research areas which were recently completed. Firstly, the synthesis of fluorinated purine analogues by cyclization reactions of heterocyclic enamines with dielectrophiles. Secondly, the development of cyclization reactions of enamines with chromones. In fact, this project went back to our earlier experiences with chromones in cyclizations with 1,3-bis(silyloxy)-1,3-butadienes. Thirdly, CH activation reactions of nitro-substituted heterocycles. In addition, during my career, I had several collaborations with medicinal chemists and in the context of this work (cancerostatic and antibacterial compounds and enzyme inhibitors), we carried out various target orientated syntheses of heterocycles which include various types of molecules. In addition, after my postdoc in carbohydrate chemistry, I was convinced that this field would be too difficult for independent research studies because of tedious purification and characterisation of the products. However, never say never. In 2006, we started a project in this field, and we developed the synthesis of N-glycosides of indigo and indirubine derivatives. The latter proved to be active against skin cancer. This field of research continued until recently but only a few students were involved. In conclusion, my research was rather diverse over the years, but when we believed we had found a ‘gold mine’ we stayed and tried to explore it as much as possible. Besides all the research and teaching, it was always an important issue for me to bring people of different cultures, religions and political systems together. Therefore, chemistry can act as a bridge.

How has the encompassing field of chemistry changed over the last 2 decades and where do you see the challenges over the next 20 years?

As I worked in various fields of research, it is difficult to answer this question. Regarding my first independent field of research (development of cyclizations of free and masked dianions), there was not much competition at the time which might be due to the fact that it was somehow quite niche. But I was very happy when the French research group of Charles Mioskovski applied a synthesis of γ-alkylidenebutenolides which I had developed. In the field of regioselective Pd catalysed coupling reactions of polyhalogenated heterocycles the competition was higher. Nowadays, it is more and more difficult to find new substrates. A very high competition I observe is for the synthesis of new, especially highly symmetric, heterocyclic core structures and their applications in the field of electronic devices (e.g. OLED) and I believe that many interesting findings will come up in the area in the coming years.

In the case of ACM reactions, also a lot is known, but I am sure that interesting applications will be published in the future. The same is true for twofold Buchwald-Hartwig reactions, domino C-C coupling / hydroamination reactions and cycloisomerisations. With regard to cyclizations of enamines and chromones it will also be possible to come up with interesting results. This is especially the case for the synthesis of fluorinated purines and other heterocycles, because of their pharmacological relevance. Regarding the anti-cancer activity of indirubines it was surprising to follow the rapid development of this rather special and interesting type of biological target molecule. Therefore, I believe that new and interesting glycosylated indirubine derivatives will be an important topic in the future.

 

Check out the other entries in our blog series here!

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20th Anniversary Blog Series: Alexandra Slawin

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from Professor Alexandra Slawin, recently retired from the University of St. Andrews who’s first contribution to OBC was in 2003, the journal’s first year. She continued to bring her X-ray crystallography expertise to 43 research papers published in the journal across the years, most recently in 2023.

 

About Alex

Alex Slawin was born in Taunton in 1961 where she went to Bishop Fox School. She started her academic journey as an undergraduate at Imperial College in 1980, moving to Loughborough University to start an independent career and establish a chemical crystallography lab. In 1999 she moved to St Andrews where she was promoted to Professor in 2002 – the first female Professor of Chemistry in the University of St Andrews. She was there over 20 years, having worked at Imperial and Loughborough before. In 2013 she was recognised as a rare woman with over 50 papers in Angewandte Chemie and in 2014 she published her 1000th paper.

She was a fellow of the RSC and RSE before retiring and stopped paying the subscriptions and is the highest ranked female on the Cambridge Crystallographic Data Centre (the international depository for X-ray structures). She has published over 1500 peer reviewed papers and has an internationally leading research profile. Whilst her children were at school in St Andrews, Alex was on the PTA then the Parent Council for Madras College in a variety of capacities. She was the manager for technicians in the School of Chemistry for a number of years and has been a pastoral advisor there for almost all her time there. Just prior to retirement, she trained (formally) to be mediator with the Mediation partnership, and was a member of the University Mediation service, participating in external and internal mediations. She has 3 children ages 29-33 so had informally mediated for many years. She retired in 2022 intending to go into dog advertising as she felt her son’s dog was endearing enough to make big bucks but decided very quickly that was a bad move.

 

First OBC paper: C. J. Moody, A. M. Z. Slawin & D. Willows, Dirhodium(ii) tetraacetate catalysed reactions of diazo thioamides: isolation and cycloaddition of anhydro-4-hydroxy-1,3-thiazolium hydroxides (thioisomünchnones), an approach to analogues of dehydrogliotoxin, Org. Biomol. Chem., 2003, 1, 2716-2722, DOI: 10.1039/b305698h

Most recent OBC paper: A. Giannoulis, K. Ackermann, A. Bogdanov, D. B. Cordes, C. Higgins, J. Ward, A. M. Z. Slawin, J. E. Taylor & B. E. Bode, Synthesis of mono-nitroxides and of bis-nitroxides with varying electronic through-bond communication, Org. Biomol. Chem., 2023, 21, 375-385, DOI: 10.1039/d2ob01863b

Favourite OBC paper: F. N. Palmer, F. Lach, C. Poriel, A. G. Pepper, M. C. Bagley, A. M. Z. Slawin & C. J. Moody, The diazo route to diazonamide A: studies on the tyrosine-derived fragment, Org. Biomol. Chem., 2005, 3, 3805-3811, DOI: 10.1039/b510653b

 

How did your research on organic systems structural determination develop over the last 20 years?

I have been a crystallographer since my final year as an undergraduate, and back then structures were principally the domain of the inorganic chemist – although organic structures were solved, it was mainly inorganic and organometallic chemists that used the results of X-ray crystallography. The advent of cheap computing and many clever algorithms to utilise crystallographic methods meant that the use of X-ray crystallography in – as it were – ‘pure’ organic chemistry to solve light atom structures and to give absolute structure determinations became possible. Since I started with just 1 Cu machine at Imperial college, I always utilised Cu radiation and when I could afford to expand, I added Mo. Back then preferring copper radiation was unusual, and occasionally I would get referees saying I should recollect using Mo, even if the crystal I had available to me were too small to be usefully collected with Mo radiation. Instead of celebrating we had really great results, the focus was on how they thought it could be ‘better’ – as if I wouldn’t want to try publishing the best I had done, rather than just shoving in any old result.

 

How has X-ray crystallography as a tool in organic chemistry changed over the last 2 decades?

Much of what I said above, applies to this. I suppose the real change is that organic chemists are now used to being able to get results with smaller crystals, get absolute structure determination, marry up the results with other techniques. For instance, for a couple of groups, I would run a crystal that gave an absolute structure determination, save the crystal and transfer it to a vial. Then they would take that crystal and do clever NMR experiments on what could be a very small sample size in order to show that the absolute structure could verify the NMR results of not only that particular structure but perhaps a whole string of results. Although you would have to speak to the chemists about that – in the altered words of Austin Powers “NMR is not my bag”.

 

Where do you foresee the challenges being in this area over the next 20 years?

Oh, if I could answer that accurately I would be using my powers to live in a tax haven such as Bermuda – where actually one of my sons does live legitimately (he’s an actuary). So maybe my answer would be to quit chemistry and go into finance, which actually might help one finance the ongoing costs of obtaining, running and maintaining high end research equipment in the face of spiralling energy costs, decreasing public interest and fashions in chemistry that bend not according to scientific need but to political initiatives. The challenges in the area I spent my working life in are not that different to all ongoing challenges in science and it needs people with passion and interest to keep going against the system rather than going with it. I am now of an age where I didn’t feel like keeping up the fight so have retired to spend my energy doing things I enjoy, rather than struggle against stuff.

 

A word on the paper you selected as your favourite in OBC

For my favourite paper I have picked one I collaborated on with Chris Moody on an early structure from the Rigaku Rotating anode/CCD system which was a small pure organic crystal collected using Mo radiation. He was a lecturer at Imperial when I was an undergraduate, I started my independent career at Loughborough when he was Head of School there and we carried on collaborations after he and I both moved to different locations. There are very many people I had long and fruitful collaborations with, but I feel Chris’ contributions are sometimes overlooked.

 

Check out the other entries in our blog series here!

Proof of why Momo, my son’s dog, could make big bucks in advertising

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20th Anniversary Blog Series: Lei Wang

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from Professor Lei Wang at Taizhou University who first published with OBC in 2009 and he has continued to support the journal with 31 articles across the years, most recently earlier this year.

 

About Lei

Education and Employment:

2019.9 – Present Distinguished Professor of Chemistry, Taizhou University, P. R. China

2012.4 – 2019.3 Secretary of the Communist Party of China, Huaibei Normal University, P. R. China

2005.2 – 2019.9 Professor of Chemistry, Huaibei Normal University, P. R. China

2005.2 – 2012.4 President of Huaibei Normal University, P. R. China

2004.6 – 2005.2 Visiting Professor of Chemistry, Mississippi State University, USA

2001.8 – 2004.6 Professor of Chemistry, Huaibei Normal University, P. R. China

1999.6 – 2001.8 Postdoctoral Research Associate at University of Tennessee, Knoxville, USA

1996.9 – 1999.6 Ph. D., Department of Chemistry, Zhejiang University, P. R. China

1995.3 – 1996.9 Professor of Chemistry, Huaibei Normal University, P. R. China

1994.2 – 1995.3 Visiting Professor of Chemistry, Western Kentucky University, USA

1982.7 – 1995.3 Assistant, Associate and Full Professor at Huaibei Normal University, China

1978.9 – 1982.7 B.S., Huaibei Normal University, P. R. China, Major in Chemistry

Research Interests:

Organic synthesis; Organometallic chemistry; Green synthetic methodology; Organic photosynthesis; Organic electrosynthesis; Organic photoelectrosynthesis

 

First OBC paper: K. Ren, M. Wang & L. Wang, Lewis acid InBr3-catalysed arylation of diorganodiselenides and ditellurides with arylboronic acids, Org. Biomol. Chem., 2009, 7, 4858-4861, DOI: 10.1039/b914533h

Most recent OBC paper: X. Hu, H. Guo, H. Jiang, R. Zheng, Y. Zhou & L. Wang, Visible-light-induced C(sp3)-H thiocyanation of pyrazoline-5-ones: a practical synthesis of 4-thiocyanated 5-hydroxy-1H-pyrazoles, Org. Biomol. Chem., 2023, 21, 2232-2235, DOI: 10.1039/d3ob00092c

Favourite OBC paper: X. Xie, P. Li, Q. Shi & L. Wang, Visible-light-induced tandem cyclization of 2-alkynylanilines with disulfides: a convenient method for accessing benzothiophenes under transition-metal-free and photocatalyst-free conditions, Org. Biomol. Chem., 2017, 15, 7678-7684, DOI: 10.1039/c7ob01747b

 

How has your research developed over the last 20 years?

In 2001, after finishing my postdoctoral research associate at the University of Tennessee, Knoxville, USA, I returned to my home university, Huaibei Coal Industry Teachers College, starting my independent research career. At that time, I began my research from zero, overcoming a variety of unimaginable difficulties in my arduous scientific research journey, including setting up my own laboratory from nothing, with only one or two undergraduate students in my group and limited money and facilities. With the support of the Chinese government, encouragement by my co-workers and the hard work of my colleagues, my research group gradually grew and grew, and my research projects began to go very smoothly in the last two decades. Now there is a big team with more than 30 post-doctorates and graduate students in my group, well equipped with instruments including 600 MHz NMR and HPLC-HRMS with generous research funding. I have now since published more than 300 papers in J. Amer. Chem. Soc., Angew. Chem. Int. Ed., Org. Lett. et al., especially including over 30 papers published in Org. Biomol. Chem. with the first paper in 20091. As a result of this, I was selected as one of the Highly Cited Researchers (Chemistry) from 2020 to 2022 in Elsevier’s list and in the World’s Top 2% of Scientists by Stanford University. In addition, I served as the President of Huaibei Normal University (originally Huaibei Coal Industry Teachers College) from 2005 to 2012, and the Secretary of the Communist Party of China in Huaibei Normal University from 2012 to 2019. During my time in those positions, we have promoted the rapid development of the university in scientific research and the quality of graduate and undergraduate students under the support of our faculties and staffs.

 

How has the encompassing field of your research changed over the last 2 decades?

Over the last two decades, my research has been focused on the methodology of organic synthesis. However, this was originally classified as analytical chemistry until 1996. Developments in organic chemistry has meant my research field has also adjusted from organometallic chemistry directed towards organic synthesis (OMCOS) to activation/functionalisation of inert chemical bonds including C-H, C-O, and C-halogen bonds, organic photosynthesis, organic electrosynthesis and organic photoelectrosynthesis to meet the need of green chemistry with atom economy, concise synthetic routes, green solvents, non-precious transition-metal catalysis and renewable energy. Our most recent publications in OBC are an example of this, focusing on organic photosynthesis and electrosynthesis2,3. However, my favourite paper that has been published in OBC is on a convenient method for accessing benzothiophenes using visible light induced tandem cyclization of 2-alkynylanilines with disulfides4 which was highlighted by SYNFACTS in 20175.

 

Where do you see the challenges being for this field over the next 20 years?

The past decade has witnessed an explosive growth in the use of photocatalytic and electrocatalytic techniques in organic synthesis, and organic photocatalysis and electrocatalysis are two powerful strategies for the construction of organic molecules that have received much attention in recent years. Electrophotocatalysis, which at its best combines to most advantageous aspects of these two approaches, has in the last five years begun to offer new avenues for synthetic chemists. Electrophotocatalysis has the ability to perform photoredox reactions without the need for large quantities of stoichiometric or superstoichiometric chemical oxidants or reductants by making use of an electrochemical potential as the electron source under relatively mild conditions. In the next 20 years, electrophotocatalysis will be a rapidly growing research frontier combining with scale-up reactions, continuous flow chemistry for high reproducibility and high-throughput experimentation. It is becoming a powerful tool for both academic and industrial chemists.

 

Check out the other entries in our blog series here!

 

1K. Ren, M. Wang & L. Wang, Lewis acid InBr3-catalysed arylation of diorgano diselenides and ditellurides with arylboronic acids, Org. Biomol. Chem., 2009, 7, 4858-4861, DOI: 10.1039/b914533h

2X. Hu, H. Guo, H. Jiang, R. Zheng, Y.-Q. Zhou & L. Wang, Visible-light-induced C(sp3)-H thiocyanation of pyrazoline-5-ones with ammonium thiocyanate to 4-thiocyanated 5-hydroxy-1H-pyrazoles, Org. Biomol. Chem., 2023, 21, 2232-2235, DOI: 10.1039/d3ob00092c

3Y. Lv, Z.-W. Hou, Y. Wang, P. Li & L. Wang, Electrochemical monofluoroalkylation cyclization of N-arylacrylamides to construct monofluorinated 2-oxindoles, Org. Biomol. Chem., 2023, 21, 1014-1020, DOI: 10.1039/d2ob01883g

4X. Xie, P. Li, Q. Shi & L. Wang, Visible-light-induced tandem cyclization of 2-alkynylanilines with disulfides: a convenient method for accessing benzothiophenes under transition-metal-free and photocatalyst-free conditions, Org. Biomol. Chem., 2017, 15, 7678-7684, DOI: 10.1039/c7ob01747b

5V. Snieckus & M. Miranzadeh, Visible-lighted-induced iron-catalyzed synthesis of 3,3-disubstituted oxindoles, Synfacts, 2017, 13, 0802, DOI: 10.1055/s-0036-1590741

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Call For Papers: Computational Organic Chemistry

Call For Papers: Computational Organic Chemistry

Guest edited by Jolene Reid, Jonathan Goodman and Judy Wu

We are delighted to announce a call for papers for our latest online themed collection in Organic & Biomolecular Chemistry on Computational Organic Chemistry guest edited by Professor Jolene Reid (University of British Columbia, Canada), Professor Jonathan Goodman (University of Cambridge, UK) and Professor Judy Wu (University of Houston, USA).

This collection in OBC is dedicated to the latest advances in Computational Organic Chemistry. This includes computational studies that provide explanations, predictions or insights for the reactivity, structure, functions and properties of organic systems. The approaches may include density functional theory, molecular dynamics and machine learning and can be applied to systems ranging from small organic molecules and organometallics to macromolecules and supramolecular constructions.

This call for papers is open to both communications (for urgent work – up to 5 pages) and full papers.

 

Open for submissions until 30th November 2023

 

If you would like to contribute to this themed collection, you can submit your article directly through the OBC online submission service. Please mention that this submission is a contribution to the Computational Organic Chemistry collection in the “Themed issues” section of the submission form and add a “Note to the Editor” that this is from the Open Call. The Editorial Office reserves the right to check suitability of submissions in relation to the scope of both the journal and the collection, and inclusion of accepted articles in the final themed issue is not guaranteed.

Please also note that all submissions will be subject to our usual rigorous peer review process, including initial assessment to ensure the high standards of the journal and acceptance is not guaranteed. Accepted manuscripts will be highlighted together in a dedicated virtual collection alongside an editorial, regardless of submission date, and there will be no delay in the publication of all accepted manuscripts into regular issues of OBC.

If you have any questions about the collection, then please contact the Editorial Office at obc-rsc@rsc.org and they will be happy to help.

With best regards,

Professor Jolene Reid (University of British Columbia, Canada)

Professor Jonathan Goodman (University of Cambridge, UK)

Professor Judy Wu (University of Houston, USA)

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20th Anniversary Blog Series: Dhevalapally B. Ramachary

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

Our next entry to the series comes from Professor Dhevalapally B. Ramachary at the University of Hyderabad who first published with OBC in 2006 and has continued to support the journal with 27 articles across the years, most recently in 2022.

 

About Ramachary

Prof. Ramachary graduated with a MSc degree in Chemistry from the University of Hyderabad and obtained a PhD in synthetic organic chemistry from the Indian Institute of Science, Bangalore in 2001. He subsequently held a postdoctoral position at the Scripps Research Institute for Catalysis, prior to joining the University of Hyderabad in January 2005, where presently he is a full professor of organic chemistry.

He has been the recipient of many awards including Fellow of the National Academy of Sciences (Allahabad, 2021), Fellow of the Royal Society of Chemistry (London, 2020) and Fellow of Indian Academy of Sciences (Bangalore, 2018). He has guided 20 PhD students, 13 PDFs and out of them, 5 got Eli Lilly & Company Asia Outstanding Thesis Awards. He is an Editorial Advisory Board Member for Organic & Biomolecular Chemistry (2013-present), European Journal of Organic Chemistry (2017-present) and Tetrahedron Chem (2021-present). He serves as a reviewer for many national and international reputed journals and is a member of many national funding committees (DST, SERB). Prof. Ramachary has published more than 113 research papers, 2 books on emerging organocatalysis areas, delivered over 130 lectures in national/international conferences and has a few chemical reactions named after him.

 

First OBC paper: D. B. Ramachary, M. Kishor & G. B. Reddy, Development of drug intermediates by using direct organocatalytic multi-component reactions, Org. Biomol. Chem., 2006, 4, 1641-1646, DOI: 10.1039/b602696f

Most recent OBC paper: A. V. Krishna & D. B. Ramachary, The seven-step, one-pot regioselective synthesis of biologically important 3-aryllawsones: scope and applications, Org. Biomol. Chem., 2022, 20, 3948-3954, DOI: 10.1039/d2ob00438k

Favourite OBC paper: D. B. Ramachary, M. Shiva Prasad, S. Vijaya Laxmi & R. Madhavachary, Asymmetric synthesis of drug-like spiro[chroman-3,3′-indolin]-2′-ones through aminal-catalysis, Org. Biomol. Chem., 2014, 12, 574-580, DOI: 10.1039/c3ob42100g

 

How has your research developed over the last 20 years?

I am incredibly pleased to share some of my thoughts on how our research began in 2005 upon joining the School of Chemistry, University of Hyderabad as faculty after my post-doctoral studies at The Scripps Research Institute. With the knowledge gained on total synthesis from my PhD days, followed by having exposure to developing reactions in newly thriving molecular catalysis during my post-doctoral research, I decided to commence my early investigation on the area of organocatalysis, which derived inspiration from the reactions performed in biological systems designed by nature and that are occurring sequentially in a consistent medium.

We, therefore, envisioned developing new organocatalytic domino cascade sequential one-pot multi-component and multi-catalytic cascade reactions. With this objective, several questions arose about how to mimic the biological systems in already existing reactions that use harsh conditions, metals, tedious workups and column purifications with the accompanying functional group intolerance in most cases. To address these challenges, we had to develop the reactions that maintain lenity with conditions useful in sequential one-pot methods by forming bonds in a greener manner by using solvents, catalysts and conditions that ensure that the conditions employed in the first reaction are affable to the following sequence of reactions. With this rationale, we were able to develop a new method for the alkylation of cyclic-1,3-diketones, a reaction not feasible with existing conditions. The soft nucleophilic centre present in cyclic-1,3-diketones when treated with a soft electrophile like methyl iodide, allyl bromide, benzyl bromide and propargyl bromide resulted in a maximum 70% yield of the desired C-alkylation product. However, when using a hard electrophile, it resulted in only O-alkylated products. With our systematic efforts, we developed a three-component reductive alkylation of CH-acids with aldehydes/ketones in the presence of an amine or amino acid catalyst by using Hantzsch ester as a reducing agent. This is a preliminary reaction to the designed sequential one-pot combination of MCRs/MCC reactions. This method has become a beneficial tool in creating various highly functionalized biologically active molecules with wide pharmaceutical applications. This diversity-orientated green one-pot synthetic strategy has received much acclaim and is recognised as the “Ramachary Reductive Coupling Reaction”.

We later added a new dimension to our research by developing push-pull dienamine catalysis to synthesise complex organic molecules. We developed a novel regioselective, one-step, cascade Claisen-Schmidt/ iso-aromatisation reaction that could furnish highly functionalized phenols in a regio-specific manner using a simple aldehyde possessing a non-enolizable carbonyl functional group with highly substituted Hagemann’s esters under diamine catalysis. It is the first example of its kind in literature where push-pull dienamines have been generated in situ and it has stood out as an excellent platform for cascade reactions.

The discovery of copper-catalysed [3+2]-cycloaddition (the 2022 Chemistry Noble Prize-Winning Reaction) for the selective synthesis of 1,2,3-triazoles evoked interest among the synthetic community due to the significance of functionalized 1,2,3-triazoles and studies of their properties being widespread. Even though the copper-catalysed click reaction has broad utility, it has some drawbacks. To address the drawbacks imminent with existing click reactions, we have developed a common metal-free, green enamine- or enolate-mediated organocatalytic click reaction for the synthesis of 1,4-disubstituted, 1,5-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles in a more sustainable manner. Unlike the copper catalyst for [3+2]-cycloaddition of different terminal alkynes with azides, we have used relatively greener conditions by using organocatalyst like proline/DBU and were able to demonstrate the [3+2]-cycloaddition between alpha-methylene carbonyl compounds (because of their wide availability, stability and acidity) as the dipolarophile source and the aryl/alkyl-azides to synthesise the substituted 1,2,3-triazoles.

In 2012, we developed an asymmetric synthesis for drug-like spiranes through reflexive-Michael reaction using 2-aminobuta-1,3-enyne catalysis under mild conditions. Functionalized spirooxindoles were furnished in good yields with excellent stereoselectivities by using an effective Tomita zipper cyclisation reaction through organophosphine catalysis on the ynones and active olefins. Later we developed asymmetric supramolecular-organocatalysis; a bio-inspired tool for high asymmetric induction where two catalysts were used synergistically to induce high enantioselectivity for constructing enantiomerically pure drug-like hexahydroxanthenes and spriodihydrocoumarins with three contiguous stereocenters from simple precursors under mild conditions. This vital tool demonstrates the synthesis of various compounds showing potent biological activities. It has become significant in understanding the pre-transition state theory in organic chemistry. The in situ generated chiral supramolecular assembly catalysts could become great future catalytic systems for more functionalized substrates.

Our group is continuously striving to develop new catalytic reactions that can become valuable tools to make organic reactions greener and sustainable while demonstrating the synthesis of more drugs and natural products in a sequential one-pot manner.

 

How has the field of organocatalysis changed over the last 2 decades?

Over the last two decades, there has been an exponential proliferation of organocatalysis in every domain of chemistry, which is evident from the ~1500 articles per year. The role of organocatalysis in the synthesis of chiral organic compounds makes it a fundamental tool in catalytic asymmetric organic synthesis, which has several advantages over metal-catalysed and enzyme-catalysed reactions like the use of elementary organic molecules such as amino acids, the use of extraordinarily mild conditions with operational simplicity, functional group tolerance and broad applicability. The contributions from Professors Carlos F. Barbas III, David W. C. MacMillan and Benjamin List in the late 2000s laid the way for a paradigm shift in expanding the area from making simple asymmetric C-C bonds to a much wider scope of bond formations (C-O, C-N, C-X, C-S, C-P, C-H) and an eventual Chemistry Nobel Prize for the area in 2021.

In organic chemistry, achieving excellent diastereo- / enantio-selectivity and construction of pure single enantiomers is not easy, except for a few reactions like the Sharpless epoxidation, Noyori hydrogenation etc. Organocatalysis is solving challenging stereoselective transformations in vital areas which include aminocatalysis, Brønsted-acid catalysis, H-bonding catalysis, N-heterocyclic carbene catalysis, ion-pairing catalysis, oligopeptide (foldamers) catalysis, SOMO-catalysis, organosuperbases/frustrated Lewis pairs promoted catalysis, bifunctional catalysis and synergistic catalysis to name a few. Numerous valuable challenging chemical asymmetric transformations are unveiled with this tool making chemical industries chiral, greener and more sustainable.

Much more is yet to be discovered with this beautiful asymmetric platform. Unifying this platform with other fields like photoredox catalysis, electrochemistry, nanochemistry, flow chemistry and solid phase synthesis will undoubtedly be revolutionary in chiral drug discovery, natural product synthesis and material chemistry. The shortcoming of organocatalysis is that it is less efficient that metal or enzyme catalysis at low parts-per-million (ppm) level catalyst loadings. Moreover, the organocatalysts are usually required in higher quantities (up to 30 mol%). Asymmetric organocatalysed reactions with extremely low catalyst loadings are one step higher in their evolution. They are the need of the hour as they would be highly appreciable in pharmaceutical industries. General challenges associated with developing low ppm-level organocatalysed reactions include the requirement of very high reaction rates, preventing catalyst poisoning from impurities/by-products, rapidity of catalyst regeneration, catalyst stability and product stability under the reaction conditions.

 

Where do you see the challenges being for this field over the next 20 years?

Although we can reaffirm that organocatalysis has become an efficient tool capable of replacing metal and enzyme catalysis, we cannot completely rule out some of its drawbacks. The most important feature of this catalysis is that it has cleverly solved most typical problems which were once thought impossible. Nevertheless, this rapidly developing catalysis has suffered disadvantages like high catalyst loading and less efficiency than the highly explored metal or enzyme catalysis at ppm level loading. Furthermore, in comparison to intricate transition metal complexes, the simple organic molecules as catalysts were thought to once be incapable of performing all types of reactions. The deliberation in employing organocatalysis is evident in several areas but it cannot achieve excellent enantioselectivities with some of the highly functionalised substrates.

Therefore, it becomes necessary for synthetic chemists to design catalytic systems and conditions in such a way that they are useful with a wide variety of substrates. Thus, the design of functionally rich catalysts is essential, and it may only be possible with in situ combining some of the known catalysts because of cost effectiveness. However, this drawback is addressed by developing reactions employing an in situ supramolecular organocatalysis approach where more than two or three catalysts are employed in the reaction and act synergistically to produce high enantioselectivities than their single catalytic counterparts. In order to develop such types of technologies, a detailed understanding of the pre-transition states, reaction mechanisms and reactivity’s of the molecules, just like the molecular designing at the cellular level becomes highly essential.

One more challenge is recycling and reusing the employed organocatalyst, especially in the case of very costly catalysts, which stands as a severe issue that needs attention. The problem of high catalytic loading comes only with costly catalysts. Therefore, wisely switching PPM and PPB level catalyst loading to achieve good turnover numbers is the need of the hour to make organocatalysis thrive ahead in the evolution of greener and more sustainable reactions.

Another challenge and advantage of organocatalysis is the ability to not require protection and de-protection of functional groups when designing sequential one-pot strategies which increases the applicability of this tool, mainly at the industrial scale-up level. Organocatalysts often employ dilute solutions, which makes the reaction industrially less feasible. Alternatively, flow/solid support systems can find an advantage in solving this problem of catalyst loading and dilution problems. Though this catalytic approach can solve many problems, there is much room still left for further exploration in solving the fascinating mysteries of organocatalysis.

 

Check out the other entries in our blog series here!

 

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20th Anniversary Blog Series: Guan-Wu Wang

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from Professor Guan-Wu Wang at the University of Science and Technology of China who first published with OBC in 2003, the journal’s first year. He has continued to support the journal with 18 articles across the years, most recently in 2022.

 

About Guan-Wu

Guan-Wu Wang obtained his BS, MS and PhD degrees from Lanzhou University in 1987, 1990, 1993, respectively. He then did his postdoctoral work at Fudan University, Kyoto University, University of Kentucky, University of Chicago and Yale University. In May of 2000 he joined the University of Science and Technology of China as a full professor. His research interests include fullerene chemistry and mechanochemistry.

First OBC paper: T.-H. Zhang, P. Lu, F. Wang & G.-W. Wang, Reaction of [60]fullerene with free radicals generated from active methylene compounds by manganese(iii) acetate dihydrate, Org. Biomol. Chem., 2003, 1, 4403-4407, DOI: 10.1039/b309939c

Most recent OBC paper: Q.-S. Liu, W.-J. Qiu, W.-Q. Lu & G.-W. Wang, Copper-mediated synthesis of fullerooxazoles from [60]fullerene and N-hydroxybenzimidoyl cyanides, Org. Biomol. Chem., 2022, 20, 3535-3539, DOI: 10.1039/d2ob00239f

Favourite OBC paper: J.-X. Li & G.-W. Wang, Novel multicomponent reaction of [60]fullerene: the first example of 1,4-dipolar cycloaddition reaction in fullerene chemistry, Org. Biomol. Chem., 2006, 4, 4063-4064, DOI: 10.1039/b612641c.

 

How has your research developed over the last 20 years?

I established my independent research group at University of Science and Technology of China in 2000. Since then, our research interests have been focused on fullerene chemistry and green organic synthesis. We initiated the free radical reactions of fullerenes mediated by Mn(OAc)3, Fe(ClO4)3 and other metal salts. Fortunately, our early papers in this field were published in the first four successive years of OBC1,2,3,4. At the same time, we also investigated the mechanochemical reactions of fullerene and non-fullerene molecules and published papers on this in OBC5,6,7. Most recently, we are interested in electrosynthesis of fullerene derivatives by employing the starting materials synthesized by our own developed methodologies and published papers in recent years in OBC reporting this8,9,10. OBC is one of my favourite journals, and we have published 18 papers in the last 20 years.

 

How has the field of mechanochemistry changed over the last 2 decades?

Mechanochemistry was not popular at all 2 decades ago, and few scientists were working on mechanochemical reactions. However, more and more scientists are gradually interested in mechanochemistry, which is now a hot research topic. Various types of mechanochemical reactions of fullerenes and non-fullerene molecules have been developed, and even applied to the synthesis of supramolecular structures including calixarenes, rotaxanes, cage compounds, and functional materials such as MOFs, COFs, Co-crystals.

 

Where do you see the challenges being for this field over the next 20 years?

The challenges in the field of mechanochemistry over the next 20 years would be the deep understanding of the reaction mechanisms probed by more state-of-art monitoring techniques and high-level theoretical computations. Another issue would be the large-scale preparation of materials which have great potential in industries.

 

Check out the other entries in our blog series here!

 

1T.-H. Zhang, P. Lu, F. Wang & G.-W. Wang, Reaction of [60]fullerene with free radicals generated from active methylene compounds by manganese(iii) acetate dihydrate, Org. Biomol. Chem., 2003, 1, 4403-4407, DOI: 10.1039/b309939c 6Z. Zhang, J. Gao, J.-J. Xia & G.-W. Wang, Solvent-free mechanochemical and one-pot reductive benzylizations of malononitrile and 4-methylaniline using Hantzsch 1,4-dihydropyridine as the reductant, Org. Biomol. Chem., 2005, 3, 1617-1619, DOI: 10.1039/b502662h
2G.-W. Wang, T.-H. Zhang, X. Cheng & F. Wang, Selective addition to [60]fullerene of two different radicals generated from Mn(III)-based radical reaction, Org. Biomol. Chem., 2004, 2, 1160-1163, DOI: 10.1039/b317084e 7X.-L. Wu, J.-J. Xia & G.-W. Wang, Aminobromination of olefins with TsNH2 and NBS as the nitrogen and bromine sources mediated by hypervalent iodine in a ball mill, Org. Biomol. Chem., 2008, 6, 548-553, DOI: 10.1039/b717333d
3G.-W. Wang & F.-B. Li, Cu(II) acetate- and Mn(III) acetate-mediated radical reactions of [60]fullerene with ketonic compounds, Org. Biomol. Chem., 2005, 3, 794-797, DOI: 10.1039/b416756b 8J.-J. Wang, H.-S. Lin, C. Niu & G.-W. Wang, The cyclopropanation of [60]fullerobenzofurans via electrosynthesis, Org. Biomol. Chem., 2017, 15, 3248-3254, DOI: 10.1039/c7ob00463j
4G-W. Wang, H.-T. Yang, C.-B. Miao, Y. Xu & F. Liu, Radical reactions of [60]fullerene with β- enamino carbonyl compounds mediated by manganese(III) acetate, Org. Biomol. Chem., 2006, 4, 2595-2599, DOI: 10.1039/b604626f 9Y. Yang, C. Niu, M. Chen, S. Yang & G.-W. Wang, Electrochemical regioselective alkylations of [60]fulleroindoline with bulky alkyl bromides, Org. Biomol. Chem., 2020, 18, 4783-4787, DOI: 10.1039/d0ob00876a
5T.-H. Zhang, G.-W. Wang, P. Lu, Y.-J. Li, R.-F. Peng, Y.-C. Liu, Y. Murata & K. Komatsu, Solvent-free reactions of C60 with active methylene compounds, either with or without carbon tetrabromide, in the presence of bases under high-speed vibration milling conditions, Org. Biomol. Chem., 2004, 2, 1698-1702, DOI: 10.1039/b403027c 10Q.-S. Liu, W.-J. Qiu, W.-Q. Lu & G.-W. Wang, Copper-mediated synthesis of fullerooxazoles from [60]fullerene and N-hydroxybenzimidoyl cyanides, Org. Biomol. Chem., 2022, 20, 3535-3539, DOI: 10.1039/d2ob00239f

 

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20th Anniversary Blog Series: Margaret Brimble

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from previous Editorial Board member Dame Margaret Brimble at the University of Auckland, who first published with OBC in 2003, the journal’s first year. She has continued to support the journal across the years with 61 articles across the years, the most any author has published with OBC.

 

About Margaret

Margaret Brimble smilingDame Margaret Brimble FRS is the Director of Medicinal Chemistry and a Distinguished Professor at the University of Auckland. She is an Associate Editor for Organic Letters, Deputy Director of the Maurice Wilkins Centre of Molecular Biodiscovery, Past-President of IUPAC Organic and Biomolecular Division III and Past-President of the International Society of Heterocyclic Chemistry. She has published >560 papers, 96 reviews and is an inventor on >50 patents.

Margaret is a Fellow of the Royal Society London, Dame Companion of the New Zealand Order of Merit and has been inducted into the American Chemical Society Medicinal Chemistry Hall of Fame. She was awarded the Rutherford, Hector and MacDiarmid medals (Royal Society NZ), the 2023 American Chemical Society Ernest Guenther Award for Natural Products Chemistry, the 2022 Royal Society of Chemistry Pedler Award for Innovation in Organic Chemistry and the BNZ Kiwinet Supreme Commercialization Award. She was also named the 2007 L’Oreal-UNESCO Women in Science laureate in Materials Science for Asia-Pacific and a 2015 IUPAC Distinguished Women in Chemistry/Chemical Engineering.

Margaret’s research focuses on the synthesis of novel bioactive natural products/antimicrobial peptides, antibody-drug conjugates and lipopeptides for cancer vaccines and new biomaterials. She discovered the drug ‘Trofinetide’ (NNZ2566) for Neuren Pharmaceuticals (www.neurenpharma.com) that was then successful in phase 3 clinical trials conducted by Acadia Pharmaceuticals (www.acadia.com) and approved by the US Food and Drug Administration (FDA) for the treatment of Rett syndrome on March 10, 2023. The drug, marketed under the name DAYBUE™, is now available for prescription in the United States.

 A second unique neurotrophic drug candidate NNZ-2591 also discovered by Professor Brimble’s lab has been demonstrated to give positive results in pre-clinical models of four additional neurodevelopmental disorders – Angelman syndrome, Pitt Hopkins syndrome, Phelan-McDermid syndrome and Prader-Willi syndrome and is entering phase 2 clinical trials for these disorders. She also co-founded the cancer immunotherapy company SapVax (Cleveland, Ohio; www.sapvaxllc.com) with US$7 million funding from BioMotiv USA that licensed her CLipPA peptide lipidation technology to develop self-adjuvanting peptide-based cancer vaccines.

 

First OBC Paper: M. A. Brimble, R. M. Davey, M. D. McLeod & M. Murphy, Synthesis of 3-azido-2,3,6-trideoxy-β-D-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin, Org. Biomol. Chem., 2003, 1, 1690-1700, DOI: 10.1039/b301449p

Most recent OBC Paper: A. D. W. Earl, F. F. Li, C. Ma, D. P. Furkert & M. A. Brimble, Stereoselective synthesis of the spirocyclic core of 13-desmethyl spirolide C using an aza-Claisen rearrangement and an exo-selective Diels–Alder cycloaddition, Org. Biomol. Chem., 21, 1222-1234, DOI: 10.1039/d2ob01992b

Favourite OBC Paper: J. Robinson & M. A. Brimble, Synthesis of the anti-Helicobacter pylori Agent (+)-Spirolaxine Methyl Ether and the Unnatural (2″S)-Diastereomer, Org. Biomol. Chem.5, 2572-2582, DOI: 10.1039/b708265g

 

How has your research developed over the last 20 years?

I started my academic career at a small agricultural university in New Zealand with limited resources and few graduate students. I worked on the synthesis of members of the pyranonaphthoquinone antibiotics that are bioreductive alkylating agents e.g kalafungin, frenolicin, nanaomycin, actinorhodin, medermycin, griseusin, cardinalin. I then moved to larger universities – first the University of Sydney for 4 years then the University of Auckland where I have worked for over 20 years. Whilst at Auckland I expanded my research to work on the synthesis of benzannulated spiroketals such as rubromycin, berkelic acid, peniphenone, paecilospirone, chaetoquadrin, spirolaxine and shellfish toxins such as spirolides, gymnodimine, pectenotoxins and portimine. In my early days at Auckland University I also carried out some peptidomimetic work that led to the discovery of the drug candidate ‘Trofinetide’ for Neuren Pharmaceuticals that was successful in phase 3 clinical trials for Rett Syndrome and has recently been approved by the FDA. This venture into peptidomimetic chemistry led me to establish a solid phase peptide chemistry group that has now become an integral part of our research programme. We are working on antibody-drug conjugates, antimicrobial and antiviral peptides, peptide-based biomaterials and peptide-based vaccines for infectious disease and cancer.

 

How has the encompassing field of your research changed over the last two decades?

Moving into peptide chemistry prompted me to combine this with my natural products synthesis work and establish a programme to synthesize complex peptide natural products that exhibit antimicrobial activity such as cadaside, malacidin, teixobactin, paenipeptin, laterocidine, brevicidine and glycopeptides (tikitericin, glycocin F and EPO). We also developed a new patented method to effect the lipidation of peptides using a thiol-ene reaction on cysteines coin ‘CLipPA’ (Cysteine Lipidation of Peptides and Amino acids). We have applied this to the field of self-adjuvanting cancer vaccines (co-founded SapVax Ltd), peptide hormones, antimicrobial lipopeptides (the polymyxins, antiviral peptides e.g anti-HBV peptides) and peptide hydrogels.

 

Where do you see the challenges being for this field over the next 20 years?

It will be interesting to see how AI impacts the design of synthetic routes to complex natural products and how automation techniques continue to help the field of natural product synthesis. Incorporation of chemoenzymatic methods into natural products synthesis will also become routine. As for solid phase peptide synthesis we have initiated some flow chemistry work to enable fast efficient production of neoantigens for personalised vaccines.

 

Check out the other entries in our blog series here!

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20th Anniversary Blog Series: Philip Gale

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

The next entry to the series comes from Professor Philip Gale at the University of Technology Sydney who first published with OBC in 2003, the journal’s first year. He has continued to support the journal with 21 articles across the years, most recently in 2023.

 

About Phil

Philip Gale in a suit smilingPhil Gale is the Deputy Dean of Science at the University of Technology Sydney. Phil was born and raised in Woolton, Liverpool (there are an unusually high number of academic chemists who originate from L25) and attended Gateacre Community Comprehensive School. He moved to the University of Oxford in 1988 to study Chemistry and remained there to undertake a DPhil under the supervision of Paul Beer in 1992. He moved as a Fulbright Scholar to the University of Texas at Austin in 1995 to work with Jonathan Sessler and subsequently was awarded a Royal Society University Research Fellowship which he took up at Oxford in 1997. While at Oxford, he co-wrote an Oxford Chemistry Primer on Supramolecular Chemistry with Paul Beer and David Smith which resulted in the Inorganic Editor of that series, Prof. John Evans from the University of Southampton inviting Phil down to give a seminar. Southampton offered Phil a continuing position as a Lecturer and Royal Society University Research Fellow, and he rose through the ranks becoming Professor of Supramolecular Chemistry in 2007 and serving as Head of Chemistry at Southampton between 2010 and 2016.

Phil then moved as Head of Chemistry to the University of Sydney in early 2017. He served as Head from 2017 to 2022 and Associate Dean International from 2020 to 2023. In April 2022 he became interim Dean of Science at Sydney and in February 2023, moved to the University of Technology Sydney as Deputy Dean of Science.

Phil and his research team have won several awards for their work including the RSC Bob Hay Lectureship, the Corday Morgan Medal and Prize, the RSC Supramolecular Chemistry Award and the 2018 Izatt-Christensen Award in Macrocyclic and Supramolecular Chemistry.

 

First OBC paper: S. Camiolo, P. A. Gale, M. B. Hursthouse & M. E. Light, Nitrophenyl derivatives of 2,5-diamidopyrroles: structural behaviour, anion binding and colour change signaled deprotonation, Org. Biomol. Chem., 2003, 1, 741-744, DOI: 10.1039/b210848h

Most recent OBC paper: M. Fares, X. Wu, D. A. McNaughton, A. M. Gilchrist, W. Lewis, P. A. Keller, A. Arias-Betancur, P. Fontova, R. Pérez-Tomás & P. A. Gale, A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death, Org. Biomol. Chem., 2023, DOI: 10.1039/d3ob00128h

Favourite OBC paper: C. J. E. Haynes, N. Busschaert, I. L. Kirby, J. Herniman, M. E. Light, N. J. Wells, I. Marques, V. Félix & P. A. Gale, Org. Biomol. Chem., 2014, 12, 62-72, DOI: 10.1039/c3ob41522h

 

How has your research developed over the last 20 years?

When I began my independent career in the late 1990s with my own research group, many anion receptor systems reported in literature were structurally complex, containing macrocyclic components and often carrying a positive charge. We focused on simplifying the structures of these systems and reported a series of acyclic receptors, including 2,5-diamidopyrroles, ortho-phenylene-based bis-ureas, dipyrromethene bis-amides and 1,3-diamidoanthraquinones. We showed that simple acyclic receptors could still retain high affinity and selectivity for particular anions. My first paper in OBC was published in 2003 in the 4th issue of volume 1. At the time I was a relatively new academic at the University of Southampton in the UK, looking at designing hydrogen bond donor motifs to bind anions. We’d noticed that pyrrole 2,5-dicarboxamides containing electron-withdrawing groups would deprotonate upon addition of fluoride which in some cases would cause a colour change. At that time (and for a while after) there were many examples of colorimetric fluoride sensors reported in the literature – this paper together with contemporaneous work from Thorri Gunnlaugsson’s group at Trinity College Dublin demonstrated that the colour changes observed with these systems may also be due to deprotonation processes. We kept an eye out for these types of acid-base reactions and reported further examples over the following years – including in 2010 an example of a receptor containing multiple hydrogen bonds affecting the pKa of a bound anion resulting in deprotonation of the anionic guest.

Over the last twenty years we have stayed with the theme of anions but moved from designing receptors to designing and testing anionophores to facilitate the transport of anions across lipid bilayer membranes. This has been a collaborative effort with many colleagues including Tony Davis and David Sheppard in Bristol, Jeff Davis in Maryland, Bradley Smith at Notre Dame, Jonathan Sessler in Austin, Roberto Quesada in Burgos, Vitor Félix in Aveiro, Rob Elmes at Maynooth University, Kate Jolliffe at the University of Sydney, Yun-Bao Jiang at Xiamen University, Ricardo Pérez-Tomás at Barcelona, and Injae Shin at Yonsei University. My group has moved during this time, first to the University of Sydney in 2017 and this year to the University of Technology Sydney.

Early work focused on producing analogues of the natural product prodigiosin – one of the most potent HCl co-transporters known. However, as with our work on anion receptors, we simplified the design of anion transporters to understand the factors that govern efficient transport. Work focused both on encapsulating tripodal tris-ureas and -thioureas and planar single ureas, thioureas and squaramides that we demonstrated are very effective transporters when fluorinated. In 2013, we published a quantitative structure activity relationship study, showing that in a series of simple thioureas with one n-hexyl substituent and a phenyl substituent with different groups in the 4-position, the lipophilicity of the receptor is the dominant molecular parameter determining effective transport, with smaller contributions from the receptors’ volume and affinity for chloride.

With our collaborators, we’ve found that anion transport into cells can trigger apoptosis and interfere with autophagy and hence these compounds may potentially have anti-cancer properties. We’ve also demonstrated that our compounds can facilitate the transport of chloride across epithelial cell membranes. This is an interesting result as chloride transport is reduced or stopped across epithelial cell membranes in patients with cystic fibrosis. The development of chloride anionophores offers the prospect of replacing the faulty chloride channels in these cells with small molecules that can perform the same function. Our latest paper in OBC, published in 2023, twenty years after the first, is a collaboration with Ricardo Pérez-Tomás where we investigate where fluorescently tagged versions of one of the most effective anion transport motifs (ortho-phenylene bis-ureas) localise in cells.

 

How has the field of supramolecular chemistry changed over the last 2 decades?

The field of supramolecular chemistry has grown and developed significantly over the last 20 years. One of the most fascinating areas has been the development of systems chemistry and the study of dissipative self-assembly. The use of fuels to form transient assemblies far from equilibrium resembles processes found in biological systems with complex dynamic behaviour. Of course, one of the highlights of the last two decades has been the award of the Nobel Prize in Chemistry in 2016 to Jean-Pierre Sauvage, Fraser Stoddart and Ben Feringa for the development of molecular machines. Another pioneer in this area is Dave Leigh at the University of Manchester, whose work on molecular knots, synthetic chemically-fuelled molecular motors and molecular robotics is always inspiring with the ingenuity and elegance of his supramolecular creations. Another leader in supramolecular chemistry is Wolf prize winner Makoto Fujita at the University of Tokyo. A standout achievement for me has been Fujita’s development of crystalline sponges which allow micrograms of compounds to be soaked into crystals and subsequent X-ray structural determination. This has allowed single crystal X-ray diffraction structures of liquids and very small quantities of materials to be obtained.

I think importantly recently we have seen a generational shift in the field with many of the first generation of supramolecular chemists approaching retirement or having already retired, a new more diverse cohort of researchers is picking up the mantle. A positive international development has been the establishment of the Women in Supramolecular Chemistry network (www.womeninsuprachem.com) which is providing a support network for women and marginalised groups working in supramolecular chemistry. A growing recognition of the importance of supramolecular chemistry is reflected in the recent decision by the Royal Australian Chemical Institute to form a new division of supramolecular chemistry alongside the more traditional areas of chemistry.

 

Where do you see the challenges being for this field over the next 20 years?

Obtaining research funding is always challenging and supramolecular chemistry is at its core, a fundamental area of chemistry which requires discovery type support to make progress. However, I think it’s important that we as a field can point to applications of supramolecular chemistry in technological processes and in medicine. This will allow us to illustrate to funders and to our academic colleagues, the cross-cutting nature of supramolecular chemistry and the many real-world problems that can be addressed using supramolecular approaches. A group of us wrote a review1 in 2021 highlighting some of these which covered medicine, sensors, remediation of chemical warfare agents, hydrometallurgy, separations and extractions, environmental remediation, self-healing materials and coatings, adhesives, and batteries. The continued translation of supramolecular chemistry to technological applications in the real-world is vital for the long-term health of our discipline.

 

Check out the other entries in our blog series here!

 

1G. T. Williams, C. J. E. Haynes, M. Fares, C. Caltagirone, J. R. Hiscock & P. A. Gale, Advances in applied supramolecular technologies, Chem. Soc. Rev., 2021, 50, 2737-2763, DOI: 10.1039/d0cs00948b

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