Scheme 21. Synthesis of tetramic acids.
Cyclative cleavage:lo resins 76 or 78 (0.108 mmol) was added 0.1 M NaOEt (2.1 mL, 0.216 mmol) and the material was heated with vigorous shaking at 85° C for 24 h.The mixtures were cooled to rt and filtered, and the resins were repeatedly washed with ethanol and CH2CI2.The combined washings were evaporated and the crude residue was dissolved in methanol (2 mL) and eluted through a COOH ion-exchange column with MeOH to yield 77 and 79 (100 %).
When N-acylation of the amino acid derivatives was performed with acylated Meldrum's acid 20, the products were 3-acyl-tetramic acids 80. The best conditions for cleavage in this case are DIPEA/dioxane (3:7) at 80° C (Scheme 22) .
The formation of phosphor moieties able to couple to carbonyl groups turned out to be a versatile method for the cyclative cleavage approach under formation of C-C double bonds. The stoichiometric phosphine oxide byproducts which must be separated from the products when performing the reaction in solution phase remain bound to the solid phase and can, there-
Was this article helpful?