Model Experiments on Surugatoxin Synthesis. IV. Construction of the Dehydrated Surugatoxin Ring System (1)

Abstract

Unexpected results in the initial experiments for the construction of the pentacyclic surugatoxin framework from debromo-nitro-ketone 9 are described in this paper. Treatment of 9 with pyruvoyl chloride in pyridine gave nitro-enol lactone 10 which was reduced with Zn/AcOH to give amino-enol lactone 11. When a solution of 11 in CH₂Cl₂ was kept at room temperature, 11 was gradually decomposed to tetrahydropteridine 13. On the other hand, 9 was transformed to amide 16 by the sequence 1) conversion to methoxymethyl enol ether 14 by the treatment with K₂CO₃ in N, N-dimethylformamide and subsequent reaction with chloromethyl methyl ether, 2) reduction of the nitro group to amine 15 (Zn/AcOH), and 3) acylation of 15 with 2-methoxyacrylic acid-dicyclohexylcarbodiimide. When 16 was treated with 20% trifluoroacetic acid in CH₂Cl₂, unexpected ring closure occurred to form tetrahydropteridine 18.