Editor’s Choice: Santanu’s recommended articles

Professor Santanu Mukherjee (Indian Institute of Science, Bangalore), recently joined the Organic & Biomolecular Chemistry team as an Associate Editor. Santanu works in the field of asymmetric catalysis, with a focus on the discovery of new enantioselective transformations. His research group investigates hydrogen bonding, Lewis base and bifunctional catalysis, and more recently, he has focused on iridium-catalyzed asymmetric allylic substitution reactions.

 

To find out more about Santanu, take a look at our recent blog welcoming him to the team.

 

Santanu has picked out a selection of his personal favourite recent OBC articles which you can read now for free*

 

Santanu’s Recommended OBC Articles:

 

Catalyst-controlled positional-selectivity in C–H functionalizations

Virendra Kumar Tiwari and Manmohan Kapur

 

 

 

An enantioselective synthesis of α-alkylated pyrroles via cooperative isothiourea/palladium catalysis

W. Rush Scaggs, Toya D. Scaggs and Thomas N. Snaddon

 

Organocatalytic asymmetric synthesis of highly substituted pyrrolidines bearing a stereogenic quaternary centre at the 3-position

Soumendranath Mukhopadhyay and Subhas Chandra Pan

 

Total synthesis of incargranine A

Patrick D. Brown and Andrew L. Lawrence

 

 

 

 

Studies toward the synthesis of strevertenes A and G: stereoselective construction of C1–C19 segments of the molecules

Tapan Kumar Kuilya, Subhendu Das, Dhiman Saha and Rajib Kumar Goswami

 

Formal [4 + 2] benzannulation of 2-alkenyl indoles with aldehydes: a route to structurally diverse carbazoles and bis-carbazoles

Ankush Banerjee, Avishek Guin, Shuvendu Saha, Anushree Mondal and Modhu Sudan Maji

 

Vinylogous acyl triflates as an entry point to α,β-disubstituted cyclic enones via Suzuki–Miyaura cross-coupling

Daria E. Kim, Yingchuan Zhu and Timothy R. Newhouse

 

 

 

 

*Access is free until 28/02/2019 through a registered RSC account.

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OBC warmly welcomes Professor Anthony Davis as our new Editorial Board Chair

We are delighted to announce the appointment of Prof. Anthony Davis as the new Organic & Biomolecular Chemistry Editorial Board Chair. Tony returns to the Board after serving for many years as an Editorial Board member and we are very pleased to welcome him to his new role as Chair.

 

Tony is a Professor of Supramolecular Chemistry at the University of Bristol, with research focusing on anion recognition and transport, carbohydrate recognition, and crystal engineering. He started his chemistry career at Oxford University, obtaining both his undergraduate degree and D.Phil (in the group of Dr Gordon Whitham), followed by two years of postdoctoral work under the supervision of Prof. Jack Baldwin. He joined the group of Prof. Albert Eschenmoser in 1981, working as a Royal Society European Exchange Fellow, before becoming a Lecturer in Organic Chemistry at Trinity College, Dublin, in 1982. In September 2000, he moved to his current institution, and you can find out more about his current group on the research group webpage.

 

Tony is also a co-founder of Ziylo, a biotechnology company focusing on the development of new treatments for diabetes patients, which was recently sold to Novo Nordisk. A second company spun out of Ziylo, Carbometrics, continues to work on carbohydrate sensing.

 

Prof. Davis is the recipient of numerous awards including the Tilden Medal and the RSC Award for Physical Organic Chemistry. He has published hundreds of articles, and you can see a selection of his great work below.

 

Upon becoming Chair, Tony commented, “OBC is a cornerstone of organic chemical publishing, and I’m delighted to take on this responsibility.”

 

Read some of Tony’s latest publications:

Maltodextrin recognition by a macrocyclic synthetic lectin

Chem. Commun., 2018, 54, 8649-8652

 

Anion transport by ortho-phenylene bis-ureas across cell and vesicle membranes

Org. Biomol. Chem., 2018, 16, 1083-1087

(Included in the 2018 OBC HOT article collection)

 

Enantioselective carbohydrate recognition by synthetic lectins in water

Chem. Sci., 2017, 8, 4056-4061

 

Synthesis and evaluation of a desymmetrised synthetic lectin: an approach to carbohydrate receptors with improved versatility

Org. Biomol. Chem., 2016, 14, 1930-1933

(Included in the 2016 OBC HOT article collection)

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Harnessing biosynthetic pathways to efficiently derivatize biologically active natural products

Nature is unrivaled in its ability to produce structurally complex molecules with high biological potency. Natural products have been used medicinally for centuries and have provided a profitable source of potential drug leads. Developing efficient strategies for their total synthesis, as well as the production of analogues, has always been challenging.

In a recent OBC publication, Professor Shuangjun Lin of Shanghai Jiao Tong University has identified a key enzyme in the biosynthesis of the natural product, Streptonigrin, a highly fictionalized aminoquinone isolated from the bacterium Streptomyces flocculus.

 

Streptonigrin has a long history and has attracted considerable attention from both the synthetic and biochemical communities due to its challenging molecular framework and potent antimicrobial and broad-spectrum anticancer activities. In the 1970’s, Streptonigrin reached phase-II clinical trials, though ultimately failed due to high levels of toxicity and side effects. Nevertheless, interest in its medicinal properties still remains, and many studies detailing its chemical and biosynthesis have been reported, with the hopes of enabling the production of Streptonigrin-based analogues, which would mitigate the natural product’s cytotoxicity while harnessing is broad biological capabilities.

Prof. Lin reports that previous genetic and biochemical studies successfully identified a key β-carboline (3) intermediate in the biosynthetic pathway of Streptonigrin. The β-carboline moiety is a common structural feature within a large group of natural and synthetic indole alkaloids however, the enzymes catalyzing their formation have not been well characterized or reported. Lin and coworkers have identified a protein, StnK2, which they propose catalyzes a Pictet-Spengler reaction responsible for β-carboline formation from (2S,3S)-β-methyl tryptophan and erythrose (Figure).

The study focussed on the biochemical characterization of StnK2 as a Pictet-Spenglerase, analyzing in detail its stereoselectivity and substrate specificity. StnK2 exhibited exclusive aldehyde specificity, though was flexible towards various tryptophan analogues. Additionally, StnK2 demonstrated high stereoselectivity, only recognizing S-enantiomers and producing the (R)-C-1 of the β-carboline scaffold.

This study has not only contributed to our knowledge of Pictet-Spenglerase enzymes, but has established a new means through which Streptonigrin analogues can be efficiently generated and their medicinal properties explored.

To find out more see:

StnK2 catalysing a Pictet–Spengler reaction involved in the biosynthesis of the antitumor reagent streptonigrin
Xiaozheng Wang, Dekun Kong, Tingting Huang, Zixin Deng and Shuangjun Lin
DOI:10.1039/C8OB02710B

For more papers from the OBC Biosynthesis Themed Collection


Victoria Corless completed her Ph.D. in organic chemistry with Prof. Andrei Yudin at the University of Toronto. Her research centered on the synthesis of kinetically amphoteric building blocks with particular emphasis on creating novel biologically active molecules. She is passionate science and communicating new discoveries to enhance science literacy.

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Introducing Professor Santanu Mukherjee, OBC Associate Editor

OBC is delighted to welcome our new Associate Editor, Professor Santanu Mukherjee, to the Editorial Board.

Santanu started his career in chemistry at R. K. Mission Residential College, Narendrapur, India, obtaining his BSc in 2000. He went on to study for his MSc in chemistry at IIT, Kanpur, 2002, before joining Professor Albrecht Berkessel at Universität zu Köln for his doctoral studies. After completing these in 2006, he worked as a postdoctoral fellow with Professor Benjamin List at Max-Planck Institut für Kohlenforschung in Mülheim an der Ruhr until 2008 and with Professor E. J. Corey at Harvard University from 2008-2010. In 2010, Santanu 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.

His research interests focus on asymmetric catalysis, with a particular emphasis on the discovery of new enantioselective transformations, and recently, on iridium-catalyzed asymmetric allylic substitution reactions. To find out more about his research interests, you can visit the group webpage.

Santanu is a recipient of numerous recognitions and awards, and has published a large number of papers in high quality journals. Below are just a few examples of these publications:

 

Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of coumarins

Chem. Sci., 2018, 9, 5767-5772,  Edge Article

“On water” catalytic enantioselective sulfenylation of deconjugated butyrolactams

Org. Biomol. Chem., 2017, 15, 6921-6925,  Paper

Nitro-enabled catalytic enantioselective formal umpolung alkenylation of β-ketoesters

Chem. Sci., 2017, 8, 6686-6690,  Edge Article

Catalytic enantioselective cascade Michael/cyclization reaction of 3-isothiocyanato oxindoles with exocyclic α,β-unsaturated ketones en route to 3,2′-pyrrolidinyl bispirooxindoles

Org. Biomol. Chem., 2016, 14, 10175-10179,  Communication

 

Submit a manuscript for Santanu to handle today

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Bristol Synthesis Meeting 2019

Organic & Biomolecular Chemistry are proud to sponsor the 2019 Bristol Synthesis Meeting, to be held in the Victoria Rooms, University of Bristol, 9th April 2019.

The meeting boasts a fantastic line up of speakers including OBC Advisory Board members Helma Wennemers (ETH Zurich) and Ilan Marek (Technion, Israel Institute of Technology).

Registration is now open, so for the full list of speakers and to register, see the Bristol Synthesis Meeting webpage.

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Novel application of fluorescent peptide displacement for small molecule screens against RNA targets

Recent advances in our understanding of RNA have expanded its role beyond just a carrier of genetic information. Modern views of RNA encompass a diverse range of molecules, which play a central role in modulating a number of important biological processes, including the progression of various cancers and nontumorigenic diseases.

In her recent OBC publication, Professor Amanda Hargrove of Duke University has created a general, high throughput screening technique for the identification of small molecule inhibitors of different RNA proteins using a fluorescence indicator displacement (FID) assay.

Small molecule RNA inhibitors offer advantages such as enhanced absorption, distribution, and oral bioavailability over commonly employed oligonucleotides used in antisense technologies. Fluorescence-based assays are widely used techniques used to screen small molecule libraries, however, the incorporation of fluorescent tags can lead to alterations in the RNA’s native structure and often pose synthetic challenges. FID, on the other hand, is a ‘tagless’ approach in which the indicator displays different fluorescent properties in the presence or absence of an oligonucleotide.

The Hargrove group implemented the Tat FID assay in order to simultaneously screen a library of small molecules against multiple RNA targets. This provides an efficient means of measuring binding affinity as well as evaluating specificity. The Tat FID assay requires a Tat peptide construct labeled with a Förster Resonance Enhancement Transfer (FRET) pair—a 5-carboxyfluorescein (FAM) at the N-terminus and 5-carboxytetramethylrhodamine (TAMRA) at the C-terminus (see figure). When the peptide is bound to RNA, the distance between fluorophores allows for excitation of FAM and emission detection from TAMRA. Displacement of the Tat peptide results in quenching of the fluorescent signal, which can be used to quantify binding affinity.

A library of 30 small molecules (including known RNA binding small molecules) was screened against four select RNA structures. The assay was successful in identifying hits for all four RNA molecules and identified indiscriminate and differential binding of individual small molecules. Binding results correlated with known literature results and statistical analysis was used to clarify the relationship between small molecule structures/RNA based on their binding affinity and selectivity.

As with any fluorescence-based assay, the Tat FID assay possesses inherent limitations. However, it has been shown to be a powerful high throughput technique as a result of its ease of operation, low concentration requirement for both ligand and target, and its ability to rapidly assess small molecule/RNA binding interactions.

To find out more see:

Fluorescent peptide displacement as a general assay for screening small molecule libraries against RNA
Neeraj N. Patwardhan, 
DOI:10.1039/C8OB02467G


Victoria Corless has recently completed her Ph.D. in organic chemistry with Prof. Andrei Yudin at the University of Toronto. Her research is centered on the synthesis of kinetically amphoteric building blocks which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules. She is passionate about communicating new discoveries to enhance science literacy.

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Sustainable fertilisers derived from canola oil and elemental sulfur

Developing efficient crop fertilisation has become an ever-growing concern given the increasing demand for global food production. Slow-release fertilisers have been developed as a strategy to increase the efficiency of crop production while minimizing nutrient waste, reducing negative environmental impacts and enhancing crop yield. Mechanisms for controlled nutrient diffusion include semi-soluble or complex forms of the nutrient, slow hydrolysis of water-soluble compounds, and encapsulation of the nutrient within semipermeable or permeable coatings for controlled solubility/release (among many others). While slow-release strategies are promising, technical limitations such as the brittle nature of inorganic coatings and composites or the imperishable nature of synthetic polymer coatings hinder their industrial utility.

In a collaborative study published by Professor Justin Chalker of Flinders University, the group sought to develop an efficient and durable slow-release fertiliser derived from canola oil and elemental sulfur. Sulfur is highly appealing given its low cost, abundance, and that it is a secondary plant nutrient and fungicide. Numerous studies and years of research, however, have demonstrated that a persistent limitation of sulfur-coated fertilizers is their brittle nature. The present study, therefore, focused on converting sulfur to a more durable polymer form to be used as a composite with or encapsulate NPK (nitrogen, phosphorous, and potassium) nutrients.

Inverse vulcanisation was used to prepare the sulfur polymer. In this process, elemental sulfur is heated to promote the production of thiyl radicals which can react with an unsaturated small-molecule cross-linker. In this case, canola oil was used as the cross-linker to form a polysulfide polymer capable of encapsulating NPK nutrients.

Elution studies in which fertiliser is placed in a soil column and conductivity of the outflow is measured demonstrated the superior capabilities of the sulfur-encapsulated NPK fertiliser in controlling NPK nutrient release relative to free NPK. A small-scale plant growth study also found that plants treated with the composites were significantly healthier and produced more fruit relative to other groups. What’s even more exciting is the fact that the canola oil polysulfide can be made from recycled cooking oil, converting food waste into valuable fertilisers.

With the rising challenge of feeding a rapidly growing population while also mitigating damaging environmental impacts, studies such as this that make significant strides toward efficient and sustainable agricultural practices are more important than ever.

To find out more see:

Sulfur polymer composites as controlled-release fertilisers 
Maximilian Mann, 
DOI:10.1039/C8OB02130A


Victoria Corless has recently completed her Ph.D. in organic chemistry with Prof. Andrei Yudin at the University of Toronto. Her research is centered on the synthesis of kinetically amphoteric building blocks which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules. She is passionate about communicating new discoveries to enhance science literacy.

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Peptide anchors for water-resistant sunscreen

The risks associated with excessive exposure to ultraviolet (UV) radiation are well studied and many national healthcare initiatives have been pushing for large-scale sun protection programs. Despite this drive for a broader public awareness, recent studies have disclosed that skin cancers, such as melanoma, basal cell carcinoma, and squamous cell carcinoma, have become the most common form of cancer worldwide, with more new cases of skin cancer diagnosed in the U.S. than breast, prostate, lung and colon cancer combined.

In a recent OBC study by Professor Ronald Raines of MIT, the researchers identify that although the risk of skin cancer and visible signs of aging can be minimized by using sunscreen, there is still a need to develop more durable, non-greasy sunscreens that are not readily washed away with water or sweat.

Sunscreens typically form a protective barrier on the skin and protect against various types of UV radiation by either absorbing or reflecting UV light before it can reach DNA. Typical absorbing filters are small aromatic compounds, such as salicylates, cinnamates, benzophenones, or derivatives of p-aminobenzoic acid.

Previous studies have been carried out wherein small molecule UV filters have been attached to lipophilic moieties to minimize the amount of sunscreen washed away during physical activity. However, such compounds have not been shown to effectively withstand ‘washing’ and are often undesirably greasy, which according to the authors diminishes public compliance to use them.

Raines and coworkers propose that collagen mimic peptides (CMPs) could be used to effectively anchor pendent UV-filters to the skin. Natural collagen contains loops and interruptions in its overall 3D structure which provide numerous binding sites for CMPs (as demonstrated in the Raines group’s previous work). Since collagen is the primary component of skin, this would provide a means for efficiently tethering UV filters to the skin in order to create an effective, water-resistant sunscreen. Raines and coworkers showed the successful anchoring of a salicylic acid bound CMP and its retention on collagen-containing skin surrogates after repeated water washes. This strategy is highly modular and provides an excellent proof-of-concept for the development of more effective and durable sunscreens to address a worldwide concern.

To find out more see:

A pendant peptide endows a sunscreen with water-resistance
Aubrey J. Ellison and 
DOI:10.1039/C8OB01773E


Victoria Corless has recently completed her Ph.D. in organic chemistry with Prof. Andrei Yudin at the University of Toronto. Her research is centered on the synthesis of kinetically amphoteric building blocks which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules. She is passionate about communicating new discoveries to enhance science literacy.

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OBC welcomes new Editorial Board member Corinna S. Schindler

We are delighted to introduce Assistant Professor Corinna S. Schindler as the newest member of our Editorial Board.

Originally from Schwaebisch Hall, Germany, Corinna carried out her undergraduate studies at the Technical University of Munich, completing her Diploma Thesis under the supervision of K. C. Nicolaou at the Scripps Research Institute in La Jolla. She then joined the Carreira group at ETH Zurich for her Ph.D., before accepting a postdoctoral position with Eric N. Jacobsen at Harvard University. In 2013 she moved to her current faculty as an Assistant Professor at the University of Michigan.

Over the course of her career, Corinna has worked in various areas of organometallic and organic synthetic chemistry. Currently, her research lab in Michigan focuses primarily on developing new synthetic methodologies to access biologically active structures, and you can find out more by visiting the group webpage.

Corinna has been recognized by numerous awards including the NSF Career Award, c&en’s Talented Twelve Award, the American Chemical Society Green Chemistry Institute GreenX: Rising Star Award and an Alfred P. Sloan Foundation Fellowship.

 

Read her publications, including:

Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors

Chem. Commun., 2015, 51, 8990-8993, DOI: 10.1039/C5CC02918J

Photoredox activation and anion binding catalysis in the dual catalytic enantioselective synthesis of β-amino esters

Chem. Sci., 2014, 5, 112-116, DOI: 10.1039/C3SC52265B

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Harnessing ring strain to drive the classically forbidden thermal [2+2] addition of cycloalkenes

The cyclobutane ring is a unique structural element found in a wide variety of biologically active natural products and synthetic molecules. Although cyclobutanes have been known for centuries, as a result of inherent ring strain, their application in synthesis has only become more popular in the last 40-50 years.

The photochemical [2+2] cycloaddition of alkenes represents a powerful strategy for the synthesis of cyclobutane rings. However, direct irradiation of cycloalkenes with UV light often leads to unwanted and difficult to control rearrangement pathways.

Professor Jimmie Weaver of Oklahoma State University proposes an alternative to direct irradiation of cycloalkenes by instead capturing energy in the form of ring strain. The Weaver group has applied their mild and efficient methodology toward the synthesis of cyclobutane rings imbedded within a C2-symmetric tricyclic framework.

It is well known that thermal [2+2] cycloadditions are ‘forbidden’ processes due to unfavourable orbital overlap of the reaction partners during the transition state. However, a common exception to this is the [π2s+π2a] addition of alkenes and ketenes. The Weaver group proposes that a thermal [π2s+π2a] cycloaddition could take place for ground state alkenes by generating a high energy intermediate, which would result in a decreased relative energy barrier for the thermal cycloaddition.

This method uses an iridium-based photocatalyst to generate the highly strained trans-cycloheptene intermediate—which possesses 27-36 kcal/mol of ring strain—in order to drive the thermal [2+2] cycloaddition of cycloheptenes and various cycloalkene substrates. Interestingly, the reaction results in four new stereocenters which are generated with excellent stereoselectivity and regioselectivity. An added advantage of using light within the visible spectrum to activate the photocatalyst minimizes competitive photochemical [2+2] addition pathways.

This study is an excellent example of the application of basic principles to drive previously inaccessible mechanistic pathways. The authors hope that their study will encourage other applications of visible light energy to drive unfavourable endergonic reactions.

To find out more see:

An elusive thermal [2+2] cycloaddition driven by visible light photocatalysis: tapping into strain to access C2-symmetric tricyclic rings
Kamaljeet Singh, 


Victoria Corless has recently completed her Ph.D. in organic chemistry with Prof. Andrei Yudin at the University of Toronto. Her research is centred on the synthesis of kinetically amphoteric building blocks which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules. She is passionate about communicating new discoveries to enhance science literacy.

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