Oleksandr

Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols

Nature 532, 7599 (2016). doi:10.1038/nature17191

Authors: Shi-Liang Shi, Zackary L. Wong & Stephen L. Buchwald

The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

Nature Chemistry. doi:10.1038/nchem.2495

Authors: Wenjing Meng, Richard A. Muscat, Mireya L. McKee, Phillip J. Milnes, Afaf H. El-Sagheer, Jonathan Bath, Benjamin G. Davis, Tom Brown, Rachel K. O'Reilly & Andrew J. Turberfield

Molecular machines that assemble polymers in a programmed sequence are fundamental to life. Now, synthetic machinery built from DNA has been used to execute a molecular program that produces peptides, or olefin oligomers, with a defined sequence. The oligomeric product is linked to a double-stranded DNA product that records the sequence of reactions that were executed.

By combining chemical knowledge with network theory and chess-like algorithms, computers can, at last, design synthetic pathways to non-trivial targets. The picture shows a cost-optimized synthesis of Taxol (large yellow node) selected by the Chematica program from amongst 400+ million possibilities in just 7 s. Red nodes are commercially available chemicals, blue are intermediates, green are side products, and yellow halos indicate regulated substances.

[Review]
Sara Szymkuć, Ewa P. Gajewska, Tomasz Klucznik, Karol Molga, Piotr Dittwald, Michał Startek, Michał Bajczyk, Bartosz A. Grzybowski
Angew. Chem. Int. Ed., April 08, 2016, DOI: 10.1002/anie.201506101. Read article

Two sides to the story: The use of two consecutive reduction and covalent addition steps leads to the monotopic and ditopic functionalization of individual graphene layers on substrates (one side blocked) as well as graphene in dispersion (both sides accessible).

[Communication]
Kathrin C. Knirsch, Ricarda A. Schäfer, Frank Hauke, Andreas Hirsch
Angew. Chem. Int. Ed., April 01, 2016, DOI: 10.1002/anie.201511807. Read article

Nature Chemistry. doi:10.1038/nchem.2472

Authors: Yang Yang, Jing Wang, Hideki Shigematsu, Weiming Xu, William M. Shih, James E. Rothman & Chenxiang Lin

Precise control of vesicle size is highly desirable both for basic biochemical research and biomedical applications. Now, monodispersed sub-100-nm vesicles with predefined sizes have been produced using a method based on membrane self-assembly within a DNA-nanostructure guide.

Dr. Tomohisa Sawada, Motoya Yamagami, Dr. Kazuaki Ohara, Prof. Dr. Kentaro Yamaguchi and Prof. Dr. Makoto Fujita

It's all about topology: Upon complexation with silver(I) the tripeptide ligand (Pro-Gly-Pro) simultaneously folds into an Ω-looped conformation and self-assembles into a discrete peptide [4]catenane with the crossing number of 12. Within the [4]catenane each of the four equivalent M₃L₃ macrocycles is interlocked with the other three rings with tetrahedral symmetry.

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