Orthoamides and Iminium Salts, LXXX [1]. C-Glycosyl Alkynecarboxylic Acid Orthoamides. Versatile Intermediates in the Synthesis of New Types of Highly Substituted C-Nucleoside Analogs

Abstract

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 14-16, 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 32-35, pyrimidines 24-31, and 2-pyridones 36-39 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.