An efficient preparation of (S)-y-isopropyl-a-methyl-P-tetramic acid has been established, and the a nucleophilicity of the acid has been also examined.In the preceding paper,' we reported the chirality transfer on the tetronic acid templates using the alkylation or the Michael reaction at the a-position.P-Tetramic acid nucleus, the nitrogen homologue of tetronic acid, has been found in the biologically active natural products, such as tirandamycin, enhroskyrine, tenuazonic acid, ikarugamycin, and althiomycin, therefore, numerous efforts to prepare this ring system have been reported.However, no example of the fundamental study on the alkylation of this acid has been reported.In this Note, we wish to repon an efficient preparation of (S)-y-isopropyl-a-methyl-pteuamic acid (1) and the chimlity transfer on the acid using the alkylation or Michael reaction at the aposition.The first method2 for the preparation of the acid is the Dieckmann cyclization of the m i & ester.This method, however, is not applicable to the preparation of optically active tetramic acid because of racemization at the y-position.3The second method4 is the condensation of amino acid with meldrum's acid to give a y-substituted a-tetramic acid.This condensation is an excellent methodfor the preparation of optically active p-tetramic acid, however, not applicable to the preparation of a,y-disubstituted tebamic acid.The third method5 is the cyclization of amino P-keto ester.This method seems to be applicable to wide variety of optically active mono-or disubstituted p-tetramic acids.Therefore, we applied the third method for the preparation of 1. Protection of amino group in L -d i n e with carbobenzyloxy chloride (CbzCI) afforded the carboxylic acid (2).Construction of the P-keto ester moiety was performed by the sequence of activation of the carboxyl with carbonyldiimidazole (CDI) followed by the substitution of the resulting imidazolide with lithium enolate of methyl propionate to give the P-keto ester (3).Finally, hydrogenolysis of 3 and spontaneous cyclization of the resulting amino ester furnished the desired tetramic acid (1) in good yield.
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