Organic & Biomolecular Chemistry Blog

In this HOT communication Liming Zhang and colleagues at Hunan University demonstrate how α-oxo gold carbenes generated via intermolecular oxidation of terminal alkynes are highly electrophilic. So much so that they can effectively abstract halogens from halogenated solvents. They rationalise that this carbene is more electrophilic than related rhodium species due to the presence of only one α-carbonyl group, meaning it is less capable of back bonding.

Liming Zhang et al. believe that because of this differnece α-oxo gold carbenes may provide new opportunities for methodology development. To exemplify this they show that synthetically useful chloro/bromomethyl ketones can be prepared in one-step from terminal alkynes, avoiding the problems of poor regioselectivity and over-halogenation experienced by previous methods.

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Electrophilicity of α-oxo gold carbene intermediates: halogen abstractions from halogenated solvents leading to the formation of chloro/bromomethyl ketones
Weimin He, Longyong Xie, Yingying Xu, Jiannan Xiang and Liming Zhang
Org. Biomol. Chem., 2012,
DOI: 10.1039/C2OB25235J

Gang Zhaoet al. from University of Science and Technology of China present highly diastereoselective and enantioselective [4 + 2] cycloadditions between allenoates and dual activated olefins catalyzed by bifunctional N-acyl aminophosphine catalysts.

To demonstrate the potential of the N-acyl aminophosphine catalysts in asymmetric phosphine mediated reactions, Gang Zhao et al. have prepared a range of synthetically valuable cyclohexene structures based on α-substituted buta-2,3-dienoates, which bear three contiguous chiral centers with good to excellent diastereoselectivities and enantioselectivities.

Take a look and let us know what you think!

This HOT OBC article will be free to access for the next 4 weeks.

Highly enantioselective [4 + 2] cycloadditions of allenoates and dual activated olefins catalyzed by N-acyl aminophosphines
Hua Xiao, Zhuo Chai, Dongdong Cao, Hongyu Wang, Jinghao Chen and Gang Zhao
Org. Biomol. Chem., 2012,
DOI: 10.1039/C2OB25295C

In this HOT OBC paper Jun O. Liu and co-workers at Johns Hopkins University School of Medicine report structure–activity relationship studies of two oxines, which have been previously identified as hits in a high-throughput screen aimed at finding new anti-angiogenic agents, by characterising different analogues in human umbilical vein endothelial cell assays. In addition they have determined the effects of a subset of oxine derivatives on human methionine aminopeptidase and sirtuin 1 activities in endothelial cells and screened a selection of the potent inhibitors of human umbilical vein endothelial cells against two other malignant cells.

Through this they have been able to identify new oxine derivatives that exhibit improved inhibitory activity against endothelial cell proliferation, and furthermore, have made the surprising finding that subtle structural alterations can lead to dramatic changes in the mechanism of action of the resulting derivatives.

For all the in-depth details of this study check out this paper today! It’s free to access for the next 4 weeks!

Substituted oxines inhibit endothelial cell proliferation and angiogenesis
Shridhar Bhat, Joong Sup Shim, Feiran Zhang, Curtis Robert Chong and Jun O. Liu
Org. Biomol. Chem.,  2012, 10, 2979–2992
DOI: 10.1039/C2OB06978D

In this HOT OBC paper Heiko Ihmels and colleagues at University of Siegen present the fluorimetric detection of Mg²⁺ and DNA with 9-(alkoxyphenyl)benzo[b]-quinolizinium derivatives. Although there are quite a few fluorescent probes that enable the detection of different analytes from the same class of compounds, probes that allow optical detection of different types of analytes are much rarer. In this paper Heiko Ihmels et al. show that a benzo[b]quinolizinium-benzo-15-crown-5 ether conjugate can be used for the detection of both Mg²⁺ and DNA by a significant light-up effect and with different emission wavelengths for the two different analytes.

The authors investigated the light-up mechanism by comparison with the photophysical properties of methoxyphenyl-substituted benzo[b]quinolizinium reference compounds, revealing that the position of the methoxy functionality had a significant influence on the emission properties of the donor–acceptor systems.

Find the full paper here. It’s FREE to access for the four weeks, so why not take a peek!

Fluorimetric detection of Mg²⁺ and DNA with 9-(alkoxyphenyl)benzo[b]quinolizinium derivatives
Maoqun Tian, Heiko Ihmels and Shite Ye
Org. Biomol. Chem., 2012, 10, 3010–3018
DOI: 10.1039/C2OB06948B

A sensing system to detect cysteine (Cys), an essential amino acid, has been developed by scientists in the US and China. Elevated levels of Cys have been associated with neurotoxicity, while Cys deficiency is involved in a number of other disorders.

The sensing system works as a fluorescent chemodosimeter, which displays discrimination for cysteine over commonly occurring analytes that would be expected to co-exist in real samples, such as homocysteine and glutathione. Moreover, the system is desirable in that it displays off-to-on response to the target analyte and does so at a desirable long wavelength, which minimises potential interference by endogenous chromophores.

Due to its simplicity and very high selectivity, this chemodosimeter can be used to detect Cys at physiological levels.

Highly rated by the reviewers and Editorial office alike, this article has been selected as ‘Hot’ and will be FREE to access for the next 4 weeks – why not read it now!

A seminaphthofluorescein-based fluorescent chemodosimeter for the highly selective detection of cysteine
Xiaofeng Yang, Yixing Guo and Robert M. Strongin
Org. Biomol. Chem., 2012, Advance Article
DOI: 10.1039/C2OB25178G, Communication

In this HOT OBC Communication Mark E. Graham, Richard J. Payne and co-workers probe the effect of a recently discovered post-translational modification of threinine of the assembly protein AP180, a protein which plays a crucial role in clathrin coated vesicle formation in synaptic vesicle endocytosis.

Using pull down experiments on AP180 peptide fragments they aimed to explore how binding to proteins in rat brain lysate is influenced by this modification.

Read the article to find out more about the peptides used and the effect of this modification on the affinity towards synaptic proteins.

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Synthesis and protein binding studies of a peptide fragment of clathrin assembly protein AP180 bearing an O-linked β-N-acetylglucosaminyl-6-phosphate modification
Mark E. Graham, Robin S. Stone, Phillip J. Robinson and Richard J. Payne
Org. Biomol. Chem., 2012, 10, 2545-2551
DOI: 10.1039/C2OB07139H

In this OBC ‘Hot paper’ John C. Vederas and coworkers describes studies on a key enzyme (DscC) in the biosynthesis of the important antibiotic D-cycloserine – commonly used against Mycobacterium tuberculosis when resistance to other antibiotics is observed.

The enzyme is proposed to be an epimerase based on sequence similarity to a known enzyme DapF (diaminopimelate epimerase), and the authors show that DscC indeed displays the predicted activity, namely O-ureidoserine racemization.

The determination of the 3D stucture of the enzyme is underway.

‘Comparison of the enzymatic residues that are responsible for recognition of the non-reacting distal site of the enzyme could lead to the ability to rationally design enzymes that can induce epimerization of other amino acids’, conclude the authors.

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Characterization of DcsC, a PLP-independent racemase involved in the biosynthesis of D-cycloserine
David Dietrich, Marco J. van Belkum and John C. Vederas
Org. Biomol. Chem., 2012, 10, 2248-2254
DOI: 10.1039/C2OB06864H,