Organic & Biomolecular Chemistry Blog

Dr Alain Wagner and Dr Guilhem Chaubet

Introducing the researchers:

Dr Guilhem Chaubet is the co-director of the Biofunctional Chemistry team in Strasbourg. He joined the CNRS as an independent researcher in 2017 after a PhD at the University of Montpellier II (2010-2013) and a postdoctoral position at the University of Oxford (2014-2017). He investigates chemical conjugation of native proteins, focusing especially on the development of new strategies.

Dr Alain Wagner was born in Saint Avold, France in 1964.  After graduate studies at Strasbourg University under the supervision of Prof.Charles Mioskowski, he took up a postdoctoral fellowship at Affymax Research, Palo Alto, working under the supervision of Prof. Peter Schultz. He entered the CNRS in 1994. In 2001, he co-funded the company Novalix, now one of largest CROs in France. He returned to academic research in 2007 to start the biofunctional chemistry team. In 2014, he co-funded Syndivia, a start-up exploiting new bioconjugations and linker technologies in the field of ADC, and a few months ago, embarked on a new adventure of single cell secretion analysis by co-funding MicroOmiX. His current research focuses on studying chemical reactivity in complex biological systems with applications in drug delivery and droplet microfluidic-based single cell analysis.

What inspired your research in this area?

This work originated almost 10 years ago, when we started investigating in-vivo drug inactivation via strain-promoted azide-alkyne cycloaddition (SPAAC). We had selected an azide analogue of warfarin as our model drug and proved that its anticoagulant activity could be neutralized in mice after injection of a PEG-containing strained alkyne. While this work ended up being published a few years ago, it was during the course of its development that we noticed this odd behaviour of SPAAC being accelerated in human plasma compared to traditional solvent mixtures. Being puzzled by this observation, we decided to dig deeper, which ultimately led to this work published in OBC.

What do you personally feel is the most interesting/important outcome of your study?

I think it is the revision of classical synthetic chemistry rules when reactions are conducted in such a complex medium rather than in a flask, where you can precisely control the environment. Bioorganic chemistry thus challenges the way chemists think about and design their experiments, which fosters innovation and originality.

What directions are you planning to take with your research in future? What are you going to be working on next?

We keep working on new methodologies to access site-specific conjugation of native proteins, which ultimately could lead to protein-selective strategies and applications of these reactions in complex biological media.

Read the full article: Plasma induced acceleration and selectivity in strain-promoted azide–alkyne cycloadditions

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members. For this month’s selection, Judy I-Chia Wu has highlighted some of her favourite recent works. Take a look at what she thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Judy’s Selection:

Water binding stabilizes stacked conformations of ferrocene containing sheet-like aromatic oligoamides

Ya-Zhou Liu, Xiao Mu, Cheih-Kai Chan, Koen Robeyns, Cheng-Chung Wang and Michael L. Singleton

Judy’s comments: “Water binding is known to play an important role in stabilizing the structures of many biopolymers such as DNA, lignin, and protein structures. Here, Singleton and co-workers show that water binding also can be used to control fluxional movements of foldamers, highlighting an underappreciated aspect of conformation control in synthetic oligomers.”

Find out more in our interview with the authors

Plasma induced acceleration and selectivity in strain-promoted azide–alkyne cycloadditions

David Warther, Enes Dursun, Marion Recher, Sylvain Ursuegui, Michel Mosser, Joanna Sobska, Wojciech Krezel, Guilhem Chaubet and Alain Wagner

Judy’s comments: “Strain-promoted azide–alkyne cycloadditions (SPAAC) are an important class of bioorthogonal reactions, but kinetic studies of these reactions have been limited to solvents and mixtures that do not reflect the environment of in vivo systems. Here, Chaubet, Wagner and co-workers report the important effects of considering a complex medium, opening doors to studying in vivo applications of SPAAC reactions.”

Find out more in our interview with the authors

Recent advances in single-benzene-based fluorophores: physicochemical properties and applications

Jaehoon Kim, Ji Hyeon Oh and Dokyoung Kim

Judy’s comments: “Organic molecule-based fluorophores are opening a new era in biology and materials science. In this review, Kim and co-workers summarize advances in the development of single-benzene-based fluorophores (SBBFs) in the past 15 years. It continues to amaze me how small and simple molecules as such can have such broad applications in chemistry!”

Meet the Editor:

Judy I-Chia Wu, OBC Editorial Board Member

Judy is a physical organic chemist and currently an Assistant Professor at the University of Houston. She received her Ph.D. in 2011 from the University of Georgia under the supervision of Professor Paul Schleyer.

Her current research interests span topics in ground and excited-state aromaticity and antiaromaticity, photochemistry, supramolecular chemistry, and enzyme catalysis.

Let’s meet our researchers:

Victoria Dimakos was born in Toronto. In 2015, she received her undergraduate degree in Chemistry and Art History at the University of Toronto. As an undergraduate, she was introduced to carbohydrate chemistry in the laboratories of Profs Mark Nitz and Mark S. Taylor. She began her graduate studies in 2015 at the University of Toronto in the Taylor group, where her research has focused on the development of site-selective functionalizations of carbohydrate derivatives using organoboron reagents. She has completed her PhD and is now conducting postdoctoral research with Prof. Stephen Newman at the University of Ottawa.

Mark S. Taylor was born in Oxford, England and grew up in Toronto. He received his B.Sc. in chemistry in 2000 from the University of Toronto. After graduate studies at Harvard University under the supervision of Prof. Eric Jacobsen, he took up a postdoctoral fellowship at MIT, working in the research group of Prof. Tim Swager. In 2007, he returned to the Department of Chemistry at the University of Toronto, where he is Professor and Canada Research Chair in Molecular Recognition and Catalysis.

What inspired you to write this Review article?

Our interest in O-arylation of carbohydrates arose by chance: Victoria observed a small amount of O-arylation during an unsuccessful attempt to conduct a organoboron-catalyzed oxidation of a carbohydrate. We recognized that this transformation might have value because methods for direct arylation of OH groups in carbohydrates are relatively rare. We wrote the review article to highlight recent discoveries from groups around the globe that have led to new methods for O-arylation of carbohydrates, and to bring attention to the issues and opportunities associated with this transformation.

What primary research are you carrying out in the area?

My group is broadly interested in developing site-selective transformations of carbohydrates, with a focus on catalytic processes. We have used organoboron catalysts and reagents for selective functionalizations of OH groups in sugars, and have recently expanded this program to include selective formation of carbon-centred radicals by hydrogen atom abstraction.

What are your thoughts on the future of this research field?

One dimension of the work described in this review article involves developing new approaches for the preparation of O-aryl glycosides, compounds with established applications in medicinal chemistry and biochemistry. These new approaches may offer complementary advantages to the more established methods. On the other hand, the products of O-arylation at non-anomeric OH groups have not been explored extensively. Considering that aryl groups are important pharmacophores, the ability to append them to carbohydrates in a direct and efficient way may create new opportunities in medicinal chemistry and other fields. Several of the discoveries highlighted in the Review have taken place at the nexus of the carbohydrate chemistry and transition metal catalysis fields, and it is likely that more exciting discoveries will be reported along this line in the future.

Read the full article: Recent advances in the direct O-arylation of carbohydrates

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

Introducing Dr Brett N. Hemric:

I grew up in a small town in Oklahoma, where my father was a science professor. Because of this, I was playing with model kits and exploring the lab at an early age. After attending Liberty University and achieving a B.S. in Biochemistry and Molecular Biology in 2013, I attended Duke University and worked with Dr. Qiu Wang, earning a Ph.D. in Organic Chemistry in 2018. I am currently a Postdoctoral Research Associate with Prof. Scott Denmark at the University of Illinois at Urbana-Champaign and I aspire to move into an assistant professor position in the future.

What inspired you to write this Review article?

I have always enjoyed alkene reactions ever since learning about them in undergraduate organic chemistry. There is something fascinating about the inherent “built-in” reactivity of carbon-carbon pi bonds toward electrophiles. In writing this review, I wanted to provide a comprehensive resource for all of the current work on amino oxygenation of alkenes, alkynes, and allenes, since this area has seen a renaissance in recent years after the seminal Sharpless amino hydroxylation work that begun in the 1970s.

What primary research are you carrying out in the area?

My doctoral work focused on alkene amino oxygenation using electrophilic nitrogen species and copper catalysis. We were able to produce a number of methods, both intramolecular and intermolecular, for the amino oxygenation of alkenes and 1,3-dienes. I am currently working in the laboratory of Dr. Scott Denmark and am also working on alkene difunctionalization, so be on the lookout for that soon!

What are your thoughts on the future of this research field?

Although there are a large number of methods in the alkene amino oxygenation literature, future methods will need to accomplish high levels of enantioselectivity on a broad range of substrates, in addition to the diastereo- and regioselectivity already present in many methods. Within the arena of alkyne and allene amino oxygenation, there are significantly fewer intentional research programs toward their functionalization and much more unexplored space for ambitious scientists to devote their efforts towards.

Read the full article: Beyond osmium: progress in 1,2-aminooxygenation of alkenes, 1,3-dienes, alkynes,and allenes

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members. For this month’s selection, Associate Editor Professor Santanu Mukherjee has highlighted some of his favorite recent works. Take a look at what he thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Santanu’s Selection: 

Mannich-type allylic C–H functionalization of enol silyl ethers under photoredox–thiol hybrid catalysis

Tsubasa Nakashima, Kohsuke Ohmatsu and Takashi Ooi

Santanu’s comment: “Silyl enol ethers are nucleophilic at α-position and their reaction with electrophiles results in α‑functionalization of carbonyls. The work described in this communication bypasses this conventional reactivity of silyl enol ethers under photoredox-thiol hybrid catalysis to effect β-functionalization of ketones through allylic C–H functionalization of cyclic and acyclic silyl enol ethers.”

Find out more in our interview with the authors

Beyond osmium: progress in 1,2-aminooxygenation of alkenes, 1,3-dienes, alkynes,and allenes

Brett N. Hemric

Santanu’s comment: “1,2-Heterodifunctionalization of olefins is an important synthetic transformation, in which 1,2-amino oxygenation occupies a special place. While osmium-catalyzed aminohydroxylation of olefins is a rather well-established method, a number of other strategies are available for carrying out 1,2-amino oxygenation of olefins, even enantioselectively. This comprehensive review beautifully summarises osmium-free 1,2‑amino oxygenation reactions not only of alkenes, but also of 1,3-dienes, alkynes, and allenes.”

Find out more in our interview with the author

Recent advances in the direct O-arylation of carbohydrates

Victoria Dimakos and Mark S. Taylor

Santanu’s comment: “O-Aryl glycosides can be found in a variety of natural products having significant bioactivity. The direct C(sp2)–O bond formation between a (hetero)arene derivative and a hydroxy group of carbohydrates presents an attractive synthetic strategy. Recent developments in this direction are reviewed in this article.”

Find out more in our interview with the authors

Tris(pentafluorophenyl)borane Catalyzed C−C and C−heteroatom Bond Formation

Gautam Kumar, Sourav Roy and Indranil Chatterjee

Santanu’s comment: “The recent emergence of tris(pentafluorophenyl)borane (BCF) as Lewis acid catalyst has led to the development of a large number of metal-free transformations. This review highlights the most recent examples of BFC-catalyzed (or co-catalyzed) transformations.”

Find out more in our interview with the authors

Meet the Editor:

Santanu Mukherjee, OBC Associate Editor ORCID: https://orcid.org/0000-0001-9651-6228 Santanu Mukherjee obtained his BSc (Chemistry Honors) from R. K. Mission Residential College, Narendrapur (2000) and MSc (Chemistry) from IIT, Kanpur (2002). After completing his doctoral studies with Professor Albrecht Berkessel at Universität zu Köln in 2006, he worked as a postdoctoral fellow with Professor Benjamin List at Max-Planck Institut für Kohlenforschung in Mülheim an der Ruhr (2006-2008) and subsequently with Professor E. J. Corey at Harvard University (2008-2010). In 2010, he returned to India to join the Department of Organic Chemistry at Indian Institute of Science, Bangalore as an Assistant Professor and was promoted to Associate Professor in 2015. He is a recipient of Thieme Chemistry Journals Award (2011), Indian National Science Academy (INSA) Medal for Young Scientists (2014) and a Fellow of the Royal Society of Chemistry (2018). His research interests primarily revolve around asymmetric catalysis with particular emphasis on the discovery of new enantioselective transformations. His research group mostly relies on hydrogen bonding, Lewis base and bifunctional catalysis. More recently, he is looking to expand his research activities in the realm of iridium-catalyzed asymmetric allylic substitution reactions.

From left to right: Tsubasa Nakashima, Kohsuke Ohmatsu and Takashi Ooi

Let’s meet the researchers!

Tsubasa Nakashima received his B.S. in 2016 and his M. S. degree in 2018 from Nagoya University under the guidance of Prof. Takashi Ooi. He is currently a Ph.D. student at Nagoya University and recipient of a JSPS Research Fellowship for Young Scientists. He was awarded the Chemical Society of Japan Student Presentation Award (2019).

Kohsuke Ohmatsu received his B.S. in 2003 and his Ph.D. in 2008 from Kyoto University under the supervision of Prof. Keiji Maruoka. He started the research in the Ooi group at Nagoya University as an assistant professor in 2008, became a lecturer in 2013, and was then promoted to an associate professor in 2015. He was awarded the Akasaki Prize (2013), the ITbM research award (2013), the Chemical Society of Japan Award for Young Chemists (2016), the Commendation for Science and Technology by MEXT, the Young Scientists’ Prize (2017), Chemist Award BCA (2020), and Thieme Chemistry Journals Award (2021).

Takashi Ooi received his B.S. in 1989 and his Ph.D. in 1994 from Nagoya University under the guidance of Prof. Hisashi Yamamoto. After postdoctoral work with Prof. Julius Rebek, Jr. (MIT, Cambridge), he joined the group of Prof. Keiji Maruoka in Hokkaido University as an assistant professor in 1995, became a lecturer in 1998, and then moved to Kyoto University as an associate professor in 2001. In 2006, he moved to Nagoya University as a full professor. Since 2013, he has been a principal investigator at the Institute of Transformative Bio-Molecules (WPI-ITbM) in Nagoya University.

What inspired your research in this area?

The characteristic features of radical reactions that have potential for transforming the way of organic synthesis led us to pursue our approach to the design of catalysts for attaining new reactivity and selectivity. Specifically, our recent research on the efficient hydrogen-atom transfer catalysis (ACS Catal. 2020, 10, 2627) is a basis of the present study, and the leading contributions by Prof. MacMillan and coworkers to the development of the photoredox and organic-molecular hybrid catalysis (e.g. J. Am. Chem. Soc. 2015, 137, 8404) greatly inspired us.

What do you personally feel is the most important outcome of your study?

The present study expands the synthetic utility of enol silyl ethers and their analogues, which are readily available, versatile reactants in organic synthesis. The Mannich-type allylic C−H functionalization and subsequent polar reactions of the aminoalkylated enol silyl ethers allows for the rapid access to structurally complex carbonyl compounds.

What directions are you planning to take with your research in future?

We are continuing the studies to expand the scope of the allylic C−H functionalization methodology by exploiting the intrinsic features of enol silyl ethers and/or their radical cations. We will also try to develop regio- or stereoselective variants of this type of transformations.

Read the full article: Mannich-type allylic C–H functionalization of enol silyl ethers under photoredox–thiol hybrid catalysis

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

From left to right: Indranil Chatterjee, Sourav Roy and Gautam Kumar

Mr. Gautam Kumar obtained his M. Tech (Chemical Science and Technology) degree from DIAT(DU)-DRDO-Pune in 2018. He joined the IC research group under the guidance of Prof. Dr. Indranil Chatterjee in July 2018 at Indian Institute of Technology, Ropar, India as a Ph.D. student. He is working on the methodology developments for organic synthesis.

Mr. Sourav Roy completed his Masters at Bidhannagar Govt. College, Bidhannagar, West Bengal State University in 2017. He joined the IC research group under the guidance of Prof. Dr. Indranil Chatterjee in July 2018 at Indian Institute of Technology, Ropar, India as a Ph.D. student. He is working on the methodology developments in organic synthesis.

Dr. Indranil Chatterjee was born in Kolkata, India in 1983. He obtained his B.Sc. from Calcutta University, India in 2006, before joining IIT Kharagpur for his M.Sc. study. In 2008 he moved to Germany for his Ph.D. study at Westfälische Wilhelms-University Muenster under the guidance of Prof. Dr. Armido Studer. After finishing his Ph.D. study in November 2011, he became a Postdoctoral fellow in the group of Prof. Paolo Melchiorre in ICIQ, Tarragona, Spain. From 2014 to 2016, he was a Post-Doc with Prof. Martin Oestreich at the Technische Universität Berlin. He is currently an Assistant Professor at the Indian Institute of Technology Ropar, India.

What inspired you to write this Review article?

The wondrous reactivity of BCF prompted us to work in this field. The versatile capability of BCF is not only restricted to FLP catalysis but extends as a potential Lewis acid to develop verities of transition-metal-free transformation. Therefore, we thought compiling all recent reports in a single frame would be beneficial to the synthetic chemistry community and to new readers looking to develop innovative synthetic methodologies and do more exploration in this blooming area of catalysis.

What primary research are you carrying out in the area?

We started our journey in the field of BCF catalysis in 2018. We were able to successfully develop“Boron Lewis Acid-Catalyzed Regioselective Hydrothiolation of Conjugated Dienes with Thiols” (ACS Catal. 2019, 9, 12, 11627–11633). This unique and high regioselectivity prompted us to explore various regioselective C−heteroatom bond forming reactions using BCF catalysis as an ongoing project.

What are your thoughts on the future of this research field?

This review collectively highlights the recent development and displays a strong prospective towards a new direction for further discovery and sustainable synthesis in this area. We hope this reactivity can be a potential alternative for transition-metal-based catalysts to discover numerous synthetic protocols in the near future with industrial applications. We expect that BCF chemistry will be explored in various C−H bond functionalization strategies and utilized as a co-catalyst in numerous asymmetric transformations.

Read the full article: Tris(pentafluorophenyl)borane Catalyzed C−C and C−heteroatom Bond Formation

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members. For this month’s selection, Associate Editor Professor Lei Liu has highlighted some of his favourite recent works. Take a look at what he thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Lei’s Selection: 

Development of functionalized peptides for efficient inhibition of myostatin by selective photooxygenation

Hideyuki Okamoto,  Atsuhiko Taniguchi,  Shoya Usami,  Masahiro Katsuyama,  Sho Konno,  Akihiro Taguchi,  Kentaro Takayama and Yoshio Hayashi

Lei’s comment: “Myostatin, a major negative regulator protein of skeletal muscle growth, has been shown to play a key role in homeostasis of skeletal muscle. To develop new approaches for myostatin-targeting therapy, a series of photooxygenation-functionalized molecules were developed through the conjugation of myostatin-binding peptide and on/off-switchable photooxygenation catalyst. One of these molecules can very efficiently inactivate myostatin through irreversible and catalytic photooxygenation. This study demonstrates a novel strategy for myostatin inhibition.”

Find out more in our interview with the authors

Cobalt-catalyzed carbonylation of the C–H bond

Lukass Lukasevics and Liene Grigorjeva

Lei’s comment: “The use of cobalt catalysts for C-H activation and functionalization reactions has received increasing attentions in recent years due to two reasons: first, cobalt is a cheap metal; second, cobalt catalysis may provide novel reactivity and selectivity. In the review article the authors surveyed the utility of high-valent cobalt catalysis in C–H carbonylation reactions, showing their applications to many pharmaceutically interesting molecules including benzamides, sulphonamides, benzylamines, aryl anilines, phenols and amino alcohols. The success of cobalt catalysis suggests the need to expand studies in the field, particularly carbonylation of the C(sp3 )–H bond.”

Find out more in our interview with the authors

DNAzymes for amine and peptide lysine acylation

Tianjiong Yao,  Jack J. Przybyla,  Peter Yeh,  Austin M. Woodard,  Hannah J. Nilsson,  Benjamin M. Brandsen and Scott K. Silverman

Lei’s comment: “Site-selective Lys modification of peptides and proteins at various sequence sites is very important to many biotechnology-related fields. The authors report a very interesting work showing that DNAzymes can be used to catalyze amine acylation, including acylation of a Lys residue in a short DNA-anchored peptide. This study not only expands the scope of DNAzyme catalysis, but also suggests the future possible applicability of DNAzymes for sequence-selective Lys modification of pharmaceutically interesting peptides and proteins.”

Find out more in our interview with the authors

Integrating abiotic chemical catalysis and enzymatic catalysis in living cells

Christopher Adamson and Motomu Kanai

Lei’s comment: “Recent experiments have indicated that abiotic catalyst modalities can achieve co-operativity with the enzymatic machinery of living cells. Studies in the direction open doors to two very exciting opportunities: First, “catalysis medicine” where synthetic catalysis is used as a bona fide pharmaceutical modality; second, ‘semi-synthetic life’ that combines the desirable features of living organisms with the unique reactivity of abiotic catalysts. This important review article provides very interesting insights into what need to be done in the coming years, a truly exciting area that would combine the powers of modern chemistry and biology.”

Find out more in our interview with the authors

Meet the Editor:

ORCID: http://orcid.org/0000-0001-6290-8602

Professor Lei Liu graduated from University of Science and Technology of China in 1999. He obtained his PhD from Columbia University (2004), and conducted post-doctoral research work at Scripps Research Institute until 2007 when he Liu joined Tsinghua University. Lei Liu works as a Professor in the Chemistry department. His research group is interested in chemical protein synthesis.