Archive for February, 2012

Review on microwave synthesis of small molecules to target TB, HIV/AIDS, malaria and hepatitis C

Mats Larhed and colleagues from the University of Uppsala provide an extremely accessible introduction to microwave synthesis in this review article, demonstrating the use of single-mode microwave synthesis for laboratory-scale preparation of small molecules.  They focus of the synthesis of potential treatments of four of the world’s most infectious diseases; tuberculosis, HIV/AIDS, malaria and hepatitis C.


Microwave-assisted synthesis of small molecules targeting the infectious diseases tuberculosis, HIV/AIDS, malaria and hepatitis C
Johan Gising, Luke R. Odell and Mats Larhed
DOI: 10.1039/C2OB06833H

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Building a nation of scientists

Goverdhan Mehta talks to Sheena Elliott and Elinor Richards about the progress of science in India and the challenges scientists face

Goverdhan Mehta is a researcher, specialising in organic synthesis. He has helped to build institutions in India – the Indian Institute of Technology, Kanpur, the University of Hyderabad, and the Indian Institute of Science, Bangalore. He was director of the Indian Institute of Science (1998-2005) and vice chancellor of the University of Hyderabad (1994-1998).

Your research is focused on organic chemistry. What attracted you to that field?

There is something intrinsically fascinating about organic chemistry. In my early high school years, when I was exposed to interesting chemical structures, I was attracted to them. I had a sense of appreciation for art and organic molecules to me provided a wonderful expression of art at a molecular level.

What are your main achievements in the field?

I have worked in many areas of organic chemistry, but it’s synthesis that’s given me the greatest pleasure. As organic chemistry advanced, different contemporary challenges came to my attention. The main driver for me to pursue those challenges was the intricacy of the target structure synthesis. There was also an element of expectation that perhaps our research might become useful to society. We continue to need new drugs for a variety of disorders, so we synthesised a large number of natural products; many of them are biologically active and it is quite possible that some of them can provide leads for new drug discovery.

Over the last few years, I have become interested in how to address a problem that the ageing population is facing – neurodegeneration. It has been shown that some natural products can slow down neurodegeneration. In some cases, there is also an indication that they can help restore lost cognitive function. So I have been working on the synthesis of such lead molecules. As I’m getting older, I recognise the need for doing something in that area!

You’ve won numerous awards. Which achievements are you most proud of?

I don’t think that awards and recognition have necessarily brought me a great sense of joy. They do bring a sense of satisfaction because your peers have recognised your work. But I don’t think any serious researcher works for awards. It is the sheer joy of research that keeps people going. Recognition has come my way, but don’t think that I can equate that with the joy of doing research.

What are the challenges facing scientists in India and how could these be overcome?

Scientists all over the world are facing challenges on two fronts. The first problem is that scientists are not being supported by society as much as they should and some governments are not always forthcoming in terms of providing budgetary support. The second problem is that scientists, and science in general, have become isolated both in terms of discipline and, to some extent, in terms of geographical location. This is being redressed now with increasing international collaborations, so in the geographical sense, the isolation is being reduced. But I think disciplinary isolation vis a vis other knowledge streams and fragmentation of science is still a serious challenge.

It is a good time for scientists in India because the government is very supportive of science. Funding is no longer as serious a problem as it is in other parts of the world. Recently, our prime minister said that the budget for science will be almost doubled over the next few years. But I’m not too sure that we as a scientific community are steering science in India in the direction that it ought to be heading. I believe that the government and the scientific community must set a goal that in the next 10 years, India will be among the world’s leading scientific countries.

What is your opinion on the perception that Indian science and research is falling behind the rest of the world, following recent comments by Prime Minister Manmohan Singh?

Prime Minister Singh’s statement referred mainly to China. China has made more progress in science and technology than India. Scientific productivity in India has increased, but not as much as in China. Since we are behind, to simply say that we are walking and walking well is not enough. We should be galloping to catch up. My judgement is that our progress is not commensurate with the support that the government is providing, and not commensurate with the capacity, capability, enthusiasm and the vibrancy that our youth have. We can achieve much more.

How do the different industries compare (the pharmaceutical industry in particular or the more general chemical industry)?

It is only over the last 10 or 12 years, since the economic reforms, that industry in India has grown at such a rate so as to be in a position to invest in research and development. I expect that investment by industry is going to rise; however, the current level of investment is not in an acceptable range. There are certain sectors – pharma, for example – and some other chemical industries, where I think India’s potential is immense, but there are some challenges with the policies that are being pursued. We have to devise a well thought out strategy.

The prime minister’s Science Advisory Council reported that there in an absence of any Indian universities among the world’s best. What is your opinion on the quality of universities in India?

I’m not a great believer in the ranking systems being followed, but the fact is that no Indian university features among the top few hundred  universities. However, if we were to look at undergraduate teaching, India has institutions that produce graduates through excellent teaching and training. The graduates are probably as good as they are anywhere else in the world. If you were to grade an institution on the quality of undergraduates, I would say that the Indian Institutes of Technology rank among the top 10 institutions in the world. But, if you bring in research and other elements, they will not feature anywhere near the top. So the quality of research is a serious problem. I think it is high time that the scientific community and scientific leadership in our country sort out an effective, implementable strategy to make a major shift.

You experienced difficulty obtaining a visa to travel to the US in 2006, when you were invited to give a lecture at the University of Florida. At the time, a report from the National Academy of Sciences in the US said that at least 3000 scientists had faced a similar problem. Have things improved since then or do you believe that the visa problem is hampering scientific progress and career development for scientists?

It was ironic that I and a leading scientist from the US, Jane Lubchenco (who at that time was president of the International Council for Science before I succeeded her), wrote an editorial about the principle of universatility of science and the visa regime in Science a few months before this happened. We wrote that it was important for the international growth of science that scientists were able to travel. Little did I realise that soon I would be a victim of this! I think the situation has improved, but a lot more needs to be done. While the US National Academy of Sciences is playing a very positive role towards this end, the academies can only do the advocacy. Eventually, it is the government and the state department of security staff that makes the final judgement.

If you have any spare time, how do you fill it?

For most scientists, and I’m no exception, your research is a hobby. What other profession can give you that pleasure and privilege? In a previous interview, I was asked what I would wish for. I said we Indians believe in rebirth and so the only wish I have is that if I were to be born again, I would be a scientist. I would like to be a chemist, hopefully a better one.

Read some of Goverdhan Mehta’s recent research:

Towards a temperature-guided molecular switch: an unusual reversible low-temperature polymorphic phase transition in a conformationally locked environment
Goverdhan Mehta and Saikat Sen, Chem. Commun., 2009, 5981
DOI: 10.1039/b905651c

Understanding the self-assembling process in crystalline cyclooctitols: an insight into the conformational flexibility of medium-sized rings
Goverdhan Mehta, Saikat Sen and Kotapalli Pallavi, CrystEngComm, 2008, 10, 534
DOI: 10.1039/b712877k

Additive induced polymorphous behavior of a conformationally locked hexol
Goverdhan Mehta, Saikat Sen and Kailasam Venkatesan, CrystEngComm, 2007, 9, 144
DOI: 10.1039/b613949c

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Top 10 Emerging Area articles from Organic & Biomolecular Chemistry

Continuing with our countdown to OBC’s 10th anniversary celebratory issue we’ve made the top cited Emerging Area articles from the journal free to access for one week:

Asymmetric organocatalysis
Jayasree Seayad and Benjamin List
DOI: 10.1039/B415217B

The golden gate to catalysis
Anja Hoffmann-Röder and Norbert Krause
DOI: 10.1039/B416516K

Organocatalysis: asymmetric cascade reactions catalysed by chiral secondary amines
Xinhong Yu and Wei Wang
DOI: 10.1039/B800245M

A hitchhiker’s guide to G-quadruplex ligands
David Monchaud and Marie-Paule Teulade-Fichou
DOI: 10.1039/B714772B

Advanced organic synthesis using microreactor technology
Batoul Ahmed-Omer, Johan C. Brandt and Thomas Wirth
DOI: 10.1039/B615072A

Diversity-oriented synthesis; a challenge for synthetic chemists
David R. Spring
DOI: 10.1039/B310752N

“Frustrated Lewis pairs”: a concept for new reactivity and catalysis
Douglas W. Stephan
DOI: 10.1039/B802575B

Synthesis of protein–polymer conjugates
Karina L. Heredia and Heather D. Maynard
DOI: 10.1039/B612355D

Catalytic asymmetric hydroamination of non-activated olefins
Kai C. Hultzsch
DOI: 10.1039/B418521H

Out of the oil bath and into the oven—microwave-assisted combinatorial chemistry heats up
Helen E. Blackwell
DOI: 10.1039/B301432K

Want to write a new emerging area that you think is going to be big in the future? Why not get in contact – we’d love to hear your ideas.

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Mouth bacteria makes metabolite that could prevent yeast infections

A bacteria present in the mouth – Streptococcus mutans – has been shown to generate the metabolite mutanobactin A by scientists from the US. They found that the metabolite inhibits biofilms formed by the fungal oral pathogen Candida albicans, which causes yeast infections.

In biofilms, pathogens are less susceptible to antibiotics, so this finding could have implications for treating yeast infections.

Fungal biofilm inhibitors from a human oral microbiome-derived bacterium
Xiaoru Wang, Lin Du, Jianlan You,  Jarrod B. King and Robert H. Cichewicz
DOI: 10.1039/C2OB06856G

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Multivalent scFvs, mitomycin C stereochemistry, peptide dendrimers and NET ligands in Issue 8

On the cover of Issue 8 we have two cancer-related articles from Jacquelyn Gervay-Hague (University of California Davis) on multivalent single chain variable fragments with increased tumor-associated antigen affinity and from Federico Gago (Universidad de Alcalá) modelling the binding of mitomycin C and analogues to DNA.

A general chemical synthesis platform for crosslinking multivalent single chain variable fragments
Joan G. Schellinger, Avinash Kudupudi, Arutselvan Natarajan, Wenjun Du, Sally J. DeNardo and Jacquelyn Gervay-Hague
DOI: 10.1039/C0OB01259A

Rationale for the opposite stereochemistry of the major monoadducts and interstrand crosslinks formed by mitomycin C and its decarbamoylated analogue at CpG steps in DNA and the effect of cytosine modification on reactivity
Juan A. Bueren-Calabuig, Ana Negri, Antonio Morreale and Federico Gago
DOI: 10.1039/C1OB06675G

The issue also contains a review from Jean-Louis Reymond and Tamis Darbre on combinatorial libraries of peptide and glycopeptide dendrimers and hot papers on creating (D)-sugars from (L)-amino acids from Paul Clarke and stilbazolium dimers as NET ligands from James N. Wilson.

View the issue

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HOT article: (D)-sugars from (L)-amino acids – a step closer to understanding the origin of life

A conundrum for anyone studying the prebiotic world is how chirality first occurred, and why D-sugars are the natural isomers, whereas natural amino acids have the L-configuration. In this hot paper Paul Clarke and Christopher Hayes from the Universities of York and Nottingham have shown how carbohydrates could have formed in prebiotic conditions by producing (D)-erythrose and (D)-threose sugars with (L)-amino acid catalysts.

Having first used proline esters to catalyse the aldol reaction of TIPS-protected glycolaldehyde in water with good yields and moderate diastereo- and enantioselectivity, the group hypothesised that other proteinogenic amino acids (i.e. amino acids found in proteins) could also catalyse this reaction.  Using N-methyl derivatives of the amino acid esters of (L)-alanine, (L)-leucine and (L)-valine they were able to produce the expected sugars, but were surprised to see that the (D)-enantiomer was the major product in all reactions. “This offers one potential explanation to account for the relationship between (L)-amino acids and (D)-sugars in nature” concludes Clarke.

This remarkable find has obviously generated a lot of interest in both scientific and the wider press: see articles in The Daily Mail, The Huffington Post, on Science Daily or the press release from University of York.

Asymmetric organocatalytic formation of protected and unprotected tetroses under potentially prebiotic conditions
Laurence Burroughs, Paul A. Clarke, Henrietta Forinto, James A. R. Gilks, Christopher J. Hayes,  Matthew E. Vale , William Wade and Myriam Zbytniewski
DOI: 10.1039/C1OB06798B

This article is also part of our joint web theme issue with ChemComm on Organocatalysis and as with all our hot articles will be free to access for 4 weeks.

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Countdown to OBC 10th Anniversary continues


As you know, we are celebrating the journal’s 10th Anniversary, and counting down the Top 10 most cited Organic & Biomolecular Chemistry research works from our different formats, according to ISI*. This week, find out which are our most cited ever Full Papers.

In addition all of these articles will be FREE for you to read until the end of next week.

10. Tandem oxidation processes for the preparation of nitrogen-containing heteroaromatic and heterocyclic compounds
Steven A. Raw,  Cecilia D. Wilfred and Richard J. K. Taylor
Org. Biomol. Chem., 2004, 2, 788-796 DOI: 10.1039/B315689C

9. Novel molecular drug carrier: encapsulation of oxaliplatin in cucurbit[7]uril and its effects on stability and reactivity of the drug
Young Jin Jeon, Soo-Young Kim, Young Ho Ko, Shigeru Sakamoto, Kentaro Yamaguchi and Kimoon Kim
Org. Biomol. Chem., 2005, 3, 2122-2125 DOI: 10.1039/B504487A

8. Organocatalytic enantioselective indole alkylations of α,β-unsaturated ketones
Wei Chen,  Wei Du,  Lei Yue,  Rui Li,  Yong Wu,  Li-Sheng Ding and Ying-Chun Chen
Org. Biomol. Chem., 2007, 5, 816-821 DOI: 10.1039/B616504D

7. Promoting laccase activity towards non-phenolic substrates: a mechanistic investigation with some laccase–mediator systems
Paola Baiocco,  Anna Maria Barreca,  Maura Fabbrini,  Carlo Galli and Patrizia Gentili
Org. Biomol. Chem., 2003, 1, 191-197 DOI: 10.1039/B208951C

6. Synthesis and photophysical evaluation of charge neutral thiourea or urea based fluorescent PET sensors for bis-carboxylates and pyrophosphate
Thorfinnur Gunnlaugsson,  Anthony P. Davis,  John E. O’Brien and Mark Glynn
Org. Biomol. Chem., 2005, 3, 48-56 DOI: 10.1039/B409018G

5. Nitrophenyl derivatives of pyrrole 2,5-diamides: structural behaviour, anion binding and colour change signalled deprotonation
Salvatore Camiolo,  Philip A. Gale,  Michael B. Hursthouse and Mark E. Light
Org. Biomol. Chem., 2003, 1, 741-744 DOI: 10.1039/B210848H

4. Comparison of topological descriptors for similarity-based virtual screening using multiple bioactive reference structures
Jérôme Hert,  Peter Willett,  David J. Wilton,  Pierre Acklin,  Kamal Azzaoui,  Edgar Jacoby and Ansgar Schuffenhauer
Org. Biomol. Chem., 2004, 2, 3256-3266 DOI: 10.1039/B409865J

3. Design, synthesis and photophysical studies of simple fluorescent anion PET sensors using charge neutral thiourea receptors
Thorfinnur Gunnlaugsson,  Anthony P. Davis,  Gillian M. Hussey,  Juliann Tierney and Mark Glynn
Org. Biomol. Chem., 2004, 2, 1856-1863 DOI: 10.1039/B404706K

2. Urea vs. thiourea in anion recognition
David Esteban Gómez,  Luigi Fabbrizzi,  Maurizio Licchelli and Enrico Monzani
Org. Biomol. Chem., 2005, 3, 1495-1500 DOI: 10.1039/B500123D

1. Organocatalysis with proline derivatives: improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions
Alexander J. A. Cobb,  David M. Shaw,  Deborah A. Longbottom,  Johan B. Gold and Steven V. Ley
Org. Biomol. Chem., 2005, 3, 84-96 DOI: 10.1039/B414742A

Why do you think these papers have been so highly cited? Do you remember when these articles were first published? Perhaps they had an impact on your own research? We’d love to find out more – tell us by posting a comment on the blog in the box below……

Have you missed the Top 10 cited OBC communications? Find them in our earlier post here.

*Top cited articles according to ISI on the 1st of February 2012

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