Reaction methodologies that can selectively target one reactive site among many that are functionally similar within a complex molecule could significantly improve synthetic efficiency and help in the identification of new drug leads. A collection of articles in this focus highlight some of the latest advances in this area, explaining the complementary approaches taken by researchers to this challenge.
doi:10.1038/nchem.1521
A collection of articles in this issue focuses on the ability to selectively perform a reaction at just one specific site in a complex molecule that contains many other similarly reactive sites.
Full Text - Take aim | PDF (168 KB) - Take aim
Subject terms: Organic chemistry | Synthesis
Pamela M. Tadross & Eric N. Jacobsen
doi:10.1038/nchem.1509
Bioactive molecules frequently contain several very similarly reactive functional groups and it can thus be difficult to cause one to react selectively. Now, two separate studies present complementary approaches to this desirable goal.
Full Text - Site-selective reactionsRemodelling by diversity and design | PDF (284 KB) - Site-selective reactionsRemodelling by diversity and design
Subject terms: Organic chemistry | Synthesis
See also: Article by Lichtor & Miller | Article by Wilcock et al.
Phillip A. Lichtor & Scott J. Miller
doi:10.1038/nchem.1469
Aspartic acid-based catalysts that are selective for oxidation of either the 2,3 position or the 6,7 position of certain isoprenols have been discovered. The catalysts emerged from a diversity-based approach employing the one-bead-one-compound libraries. The site-selectivity of the catalysis seems to derive from the hydroxyl group in the substrate, although the details of this are not yet known.
Abstract - Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation | Full Text - Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation | PDF (842 KB) - Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation | Supplementary information | Chemical compounds
Subject terms: Catalysis | Organic chemistry | Synthesis
See also: News and Views by Tadross & Jacobsen
Brandon C. Wilcock, Brice E. Uno, Gretchen L. Bromann, Matthew J. Clark, Thomas M. Anderson & Martin D. Burke
doi:10.1038/nchem.1495
Site-selective functionalizations of complex small molecules can generate targeted derivatives with exceptional step-efficiency, but general strategies for maximizing selectivity in this context are rare. Investigations with the ion-channel-forming natural product amphotericin B have revealed that site-selectivity can be tuned by simply modifying the electronic nature of the reagents.
Abstract - Electronic tuning of site-selectivity | Full Text - Electronic tuning of site-selectivity | PDF (477 KB) - Electronic tuning of site-selectivity | Supplementary information | Chemical compounds
Subject terms: Catalysis | Organic chemistry | Synthesis
See also: News and Views by Tadross & Jacobsen
Scott K. Silverman
doi:10.1038/nchem.1468
Nucleic acid aptamers have been employed to shield small molecules so that one among many similar reactive functional groups can be modified. This provides access to new chemical entities with potentially interesting properties while avoiding the use of covalent protecting groups.
Full Text - Selective functionalizationShields for small molecules | PDF (290 KB) - Selective functionalizationShields for small molecules
Subject terms: Organic chemistry | Synthesis
See also: Article by Bastian et al.
Andreas A. Bastian, Alessio Marcozzi & Andreas Herrmann
doi:10.1038/nchem.1402
Selective modifications of structurally complex molecules bearing multiple reactive functional groups often require cumbersome multistep synthetic efforts. Here, aptameric protective groups based on short RNA sequences are described — they bind to neamine antibiotics, simultaneously protecting several functionalities and enabling regio- and chemoselective functionalizations.
Abstract - Selective transformations of complex molecules are enabled by aptameric protective groups | Full Text - Selective transformations of complex molecules are enabled by aptameric protective groups | PDF (749 KB) - Selective transformations of complex molecules are enabled by aptameric protective groups | Supplementary information | Chemical compounds
Subject terms: Organic chemistry | Synthesis
See also: News and Views by Silverman
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