The structure of surugatoxin (1) is characterized by a highly functionalized spirooxindole moiety fused to a tetrahydropteridine ring. To establish a method for the construction of this unique ring system, the synthesis of 5'-ethoxycarbonyl-3'-hydroxy-3'-methyl-2-oxoindoline-3-spiro-4'-piperidine-2'-one (5) was first examined as a model compound corresponding to the spiro-oxindole moiety of 1. The procedure described in this paper involves the preparation of the spiro-oxindole 5 from ethyl 3-amino-2-(2-oxo-3-indolinyl) propionate hydrochloride (3) by acylation with 2-methoxyacrylic acid-dicyclohexylcarbodiimide followed by acidic hydrolysis (1% HCl-EtOH) and subsequent ring closure of the resulting pyruvoyl amide 4 to 5a-d as a separable mixture of four stereoisomers under basic conditions [tris buffer (pH 8.0)-EtOH or NH4OH-EtOH].
