- A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles
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Here we show a seven-step chemical synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed.
- Stress, Cedric J.,Sauter, Basilius,Schneider, Lukas A.,Sharpe, Timothy,Gillingham, Dennis
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supporting information
p. 9570 - 9574
(2019/06/24)
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- A short scalable route to (-)-α-kainic acid using Pt-catalyzed direct allylic amination
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An increased supply of scarce or inaccessible natural products is essential for the development of more sophisticated pharmaceutical agents and biological tools, and thus the development of atom-economical, step-economical and scalable processes to access these natural products is in high demand. Herein we report the development of a short, scalable total synthesis of (-)-α-kainic acid, a useful compound in neuropharmacology that is, however, limited in supply from natural resources. The synthesis features sequential platinum-catalyzed direct allylic aminations and thermal ene-cyclization, enabling the gram-scale synthesis of (-)-α-kainic acid in six steps and 34% overall yield.
- Zhang, Ming,Watanabe, Kenji,Tsukamoto, Masafumi,Shibuya, Ryozo,Morimoto, Hiroyuki,Ohshima, Takashi
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supporting information
p. 3937 - 3941
(2015/10/19)
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- Generation, electrocyclic ring opening, and unprecedented conversion of a 3-acylaminoazetinone into cis-3,4-disubstituted azetidinones
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An attempt to synthesize the nucleus of cefaclor by insertion of an appropriately functionalized rhodium carbene into a β-lactam N-H bond leads instead to attack at sulfur, followed by fragmentation into a four-membered thietanone and a four-membered 3-acylaminoazetinone. The azetinone undergoes electrocyclic ring opening, with a calculated half-life of 11 s at 40°C, to a trans-disubstituted vinyl isocyanate, but can be trapped by saturated, unsaturated allylic and benzylic alcohols to form 3,4-disubstituted azetidinones in which the cis- isomer predominates.
- Wolfe,Ro,Shi
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p. 1259 - 1271
(2007/10/03)
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