Organic & Biomolecular Chemistry Blog

Terpenes and other polycycles are very common in nature and as many are biologically active, have been a key target for synthetic organic chemists. Rama Heng and Samir Zard from Ecole Polytechnique in France have demonstrated a general approach to polycyclic structures featuring the direct formation of six-, seven-, and eight-membered rings. This very powerful, yet concise and highly flexible, approach to both fused and bridged polycyclic structures overcomes the limitations imposed by intrinsically slow radical transformations, opening numerous synthetic opportunities. Our referees were very enthusiastic about this paper and we think you will be too – expect to see more about this exciting new method!

This HOT article is available free until 21st April 2011! Read it today in OBC.

A flexible, unified radical-based approach to polycyclic structures
Rama Heng and Samir Z. Zard
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB00024A

Researchers from Kaohsiung Medical University, Taiwan, have synthesised and tested a number of 2,3-diarylquinoline derivatives for anticancer activities, one of which showed significant potential preventing cell growth in certain cancer cell lines.

Cherng-Chyi Tzeng and colleagues synthesised the 2,3-diarylquinoline derivatives as part of a continuing study to explore potent anticancer drug candidates.  The quinoline skeleton is prevalent in many natural and synthetic heterocycles with a wide range of biological effects, including antitumor activity.  The structures of tamoxifen and combretastatin A-4, two potent anticancer agents, were modified to include the quinoline moiety and various side chains to improve their activity.

Testing against six cancer cell lines, including human hepatocelluar carcinoma, non-small cell lung cancer and breast cancer, revealed one compound that was more active than tamoxifen.  6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline-otherwise known in this paper as the more manageable 16b-was shown to induce cell cycle arrest at the G2/M phase, resulting ultimately in cell death in half of the tested cell lines.  Work is ongoing to optimise the structure.

This HOT article is free to access for the next month – download it today!

Synthesis and antiproliferative evaluation of 2,3-diarylquinoline derivatives
Chih-Hua Tseng, Yeh-Long Chen, Kuin-Yu Chung, Chi-Huei Wang, Shin-I Peng, Chih-Mei Cheng and Cherng-Chyi Tzeng
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01225D

Although the presence of ozone and NO_x gases (i.e. NO^. and NO₂^.) are often linked to an increase in respiratory conditions such as asthma, the mechanism by which these pollutants cause respiratory distress is still not clear. Interestingly, the highly reactive NO₃^. (formed in the atmosphere at night by reaction of O₃ and NO₂^.) has been somewhat overlooked as a possible respiratory irritant despite numerous studies on its role in the atmosphere.

In this HOT paper Uta Wille and colleagues at the University of Melbourne follow up a previous study published in Chem. Comm. which identified the products of the reaction of the NO₃ radical with amino acids.  Now, they have simulated the exposure of proteins present at the surface of the respiratory tract to a number of environmental pollutants, determining clear reaction pathways resulting in aromatic ring nitration of the amino acids studied.  They note that nitrated aromatic amino acids are often observed in a wide range of inflammatory-immune responses such as asthma and cystic fibrosis, leading them to suggest that the NO₃ radical could actually be the real culprit in certain pollution-related diseases.

You can read the full details of this interesting study online here (it’s free to access for the next month!).

This paper is included in the OBC special we themed issue on radical chemistry that will be published soon. Keep an eye on it!

Damage of aromatic amino acids by the atmospheric free radical oxidant NO3˙ in the presence of NO2˙, N2O4, O3 and O2
Catrin Goeschen, Natalia Wibowo, Jonathan M. White and Uta Wille
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01186J

And the previous Chem. Comm. paper can be found here:

Can the night-time atmospheric oxidant NO3˙damage aromatic amino acids?
Duanne C. E. Sigmund and Uta Wille
Chem. Commun., 2008, 2121-2123
DOI: 10.1039/B803456G