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Z. Naturforsch. 2012, 67b, 699 – 716
doi:10.5560/ZNB.2012-0108
Orthoamides and Iminium Salts, LXXX. C-Glycosyl Alkynecarboxylic Acid Orthoamides. Versatile Intermediates in the Synthesis of New Types of Highly Substituted C-Nucleoside Analogs
Konstantin Drandarov1 and Willi Kantlehner1,2
1 Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
2 Fakultät Chemie/Organische Chemie, Hochschule für Technik und Wirtschaft, Beethovenstr. 1, D-73430 Aalen, Germany
Reprint requests to Prof. Dr. Willi Kantlehner. Fax: +49(7361)5762250. E-mail: willi.kantlehner@htw-aalen.de
Received April 24, 2012 / published online July 18, 2012
Dedicated to Professor Christian Vogel on the occasion of his 60th birthday
The C-glycosyl alkynecarboxylic acid orthoamides 22 and 23 are proposed as versatile precursors for the synthesis of new types of C-nucleoside analogs. The new synthetic strategy includes alkynylation of protected aldoses 13 or ketoses by Grignard ethynylation or Barbier propargylation, O-protection of the resulting alkynols 1416, and nucleophilic addition of the metalated protected terminal alkynes 20 and 21 to peralkylguanidinium salt 2 to afford the corresponding alkynecarboxylic acid orthoamides 22 and 23, which in reactions with mono or bis-nucleophiles could serve as building blocks for the construction of a wide variety of C-nucleoside-like binary conjugates. All the steps are demonstrated on 2,4,3,5-bis(4-methoxybenzylidene)-protected l-xylose 11 as a model compound. The synthesis of a representative series of C-glycosidic conjugates of highly substituted “push-pull” 1,3-butadienes 3235, pyrimidines 2431, and 2-pyridones 3639 is included. The stereochemistry of all described compounds is established by 2D-NMR techniques. A general character of the proposed synthetic strategy, when applied to different appropriately protected sugar derivatives, is suggested, and a biomedical applicability of the described type of conjugates is expected.
Key words: N,N,N′,N′,N′′,N′′-Hexamethylguanidinium Chloride, Alkynecarboxylic Acid Orthoamides, O-Protected Aldose, Ethynylation, Propargylation, Stereochemical Assignment, C-Nucleosides
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