Organic & Biomolecular Chemistry Blog

Supplying an organism with modified precursor materials for biosynthesis is a great way of hijacking the synthetic machinery of an organism to make the compounds you want. In this paper Cormac Murphy and colleagues from University College Dublin and Ecole Normale Superieure demonstrate that precursor-directed biosynthesis is a convenient way to create analogs of rumbrin with tunable potency and selectivity, also showing that the 3-chloropyrrole moiety is not absolutely essential for biological activity in this class of polyenes. One of the compounds prepared showed dramatically improved activity against lung cancer cells.

Interested? Read this article in OBC, it is free to access for the next four weeks!

Production of anticancer polyenes through precursor-directed biosynthesis
Benjamin R. Clark, Stephen O’Connor, Deirdre Fox, Jacques Leroy and Cormac D. Murphy
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C1OB05667K

The enormous success of antibiotics is seriously threatened by the development of resistance to many drugs available on the market. So the search for new antibiotics that are less prone to resistance is on.

Antimicrobial peptides (AMPs) are a possible solution that has attracted considerable attention but they have some drawbacks including high cost of manufacturing. Now Steven Firestine and colleagues at Wayne State University in the US have examined the potential of a new class of benzophenone-based membrane targeted antibiotics (BPMTAs).

Firestine shows that these agents release potassium ions from treated bacteria which  results in disruption of the bacterial membrane potential. This membrane-targeted disruption means that BPMTAs have excellent activity against antibiotic-resistant strains like MRSA and VRSA.

The team have demonstrated the promising potential of these agents by using them to cure mice of a lethal MRSA infection. They were also unable to develop a mutant resistant to the agents.

Interested? Read the article in OBC that is free to access for the next four weeks!

Examination of a synthetic benzophenone membrane-targeted antibiotic
Sunil K. Vooturi, Mahender B. Dewal and Steven M. Firestine
Org. Biomol. Chem., 2011, DOI: 10.1039/C1OB05643C

The butenolide skeleton is one of the more common to natural products and bioative compounds, thus its synthesis has afforded much attention from synthetic chemists in recent years.  Here, Xiamong Feng and colleagues from the Key Laboratory of Green Chemistry and Technology at Sichuan University have devised a simple route that affords the desired γ-butenolide compounds in high yields with high levels of selectivity.

By using a chiral N,N‘-dioxide-scandium catalyst in an asymmetric vinylogous Mukaiyama–Michael reaction they were able to form highly functionalized chiral γ-substituted butenolides with broad substrate scope, with up to 92% ee.  The pathway is air stable and produces product on a gram scale.

For the full details download the article – it’s free to access for the next four weeks:

Highly enantioselective synthesis of γ-substituted butenolides via the vinylogous Mukaiyama–Michael reaction catalyzed by a chiral scandium(III)–N,N′-dioxide complex
Qi Zhang, Xiao Xiao, Lili Lin, Xiaohua Liu and Xiaoming Feng
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05558E

New potentially useful therapeutic tools for the sexually transmitted HIV infection have been identified by Anna Bernardi at the University of Milan, Franck Fieschi and colleagues in France, Spain and Italy.

DC-SIGN and Langerin are two C-type lectins involved in the initial steps of HIV infection: the former acts as a viral attachment factor and facilitates viral invasion of the immune system, while the latter has a protective effect. Bernardi and Fieschi have successful synthesised potential antiviral compounds targeted against DC-SIGN using a common fucosylamide anchor.

Their DC-SIGN affinity was found to be similar to that of the natural ligand Lewis-X (LeX). The compounds were also found to be selective for DC-SIGN and to interact only weakly with Langerin. All these results point to the potential for these molecules to be used as therapeutic tools to fight the disease.

This hot piece of synthesis is currently free to access for four weeks:

Second generation of fucose-based DC-SIGN ligands : affinity improvement and specificity versus Langerin
Manuel Andreini, Daniela Doknic, Ieva Sutkeviciute, José J. Reina, Janxin Duan, Eric Chabrol, Michel Thepaut, Elisabetta Moroni, Fabio Doro, Laura Belvisi, Joerg Weiser, Javier Rojo, Franck Fieschi and Anna Bernardi
Org. Biomol. Chem., 2011, DOI: 10.1039/C1OB05573A,

A new nucleophilic heterocyclic carbene mediated transformation of 2H-chromene-3-carboxaldehydes has been reported by Vijay Nair, CSIR, et al.

The team were attempting to make endocyclic homoenolates from 2H-chromene-3-carboxaldehyde, but instead discovered a novel transformation which resulted in 3-methyl coumarin.  Coumarins have demonstrated important bioactives and therefore the group envisage that this reaction may be a useful future route to coumarin derivatives.

This hot piece of synthesis is currently free to access for four weeks:

A novel NHC-catalyzed transformation of 2H-chromene-3-carboxaldehydes to 3-methyl-2H-chromen-2-ones
Vijay Nair, C. R. Sinu, R. Rejithamol, K. C. Seetha Lakshmi and Eringathodi Suresh
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05325F