WERNER HEW, KARLDITTMER AND STANLEY J. CRISTOL
504
VOl. 70
[CONTRIBUTIONFROM THE DEPARTMENT OF CHEMISTRY, UNIVERSITY OF COLORADO]
Alkylation of Substituted Malonic and Cyanoacetic Esters with 2-Diamethylaminomethylpyrrole. A Proposed Synthesis of p-2-Pyrrolealanine1 BY WERNER H E R ZKARL ,~ DITTMER AND STANLEY J. CRISTOL P-2-Thienylalanine3s4t5 and P-2-furylalanine6 have been shown to inhibit microbial growth, presumably due to their structural similarity to phenylalanine. The corresponding nitrogen analog, /3-2-pyrrolealanine, is not described in the literature. As part of a program to correlate the structure of amino acids with their biological activity, it seemed desirable to prepare this substance so that it might be available for microbiological study. €IC-
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Purc P-2-pyrrolealanine could not be isolated, but fractions containing it were obtained. The amino acid was characterized by its phenylurea derivative. These fractions showed strong inhibition of growth of certain microorganisms, and this inhibition was found to be reversed by phenylalanine. Alkylation with Dimethylaminomethylpyrrole. -The scheme outlined for the preparation of p-2-pyrrolealanine was
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Attempts to synthesize p-2-pyrrolealanine by condensation of 2-pyrrolealdehyde with compounds containing active methylene groups' were abandoncd when adaptation of recently-developed methods for the synthesis of tryptophan**g~*O appeared more proniisipg. The present paper describes the use of 2-di~nethylaminometliylpyrrole~in alkylation reactions with ethyl malonate, ethyl cyanoacetate, ethyl acctsmidomalonate, ethyl acetamidocyanoacetate, and ethyl phthalimidomalonate and hydrolysis experiments of such of these products as were intermediates for the projected synthesis. (1) This work was supported in part under a contract from the Office of Naval Research. ( 2 ) Present address: Departmeut of Chemistry, University of Illinois. Url,aiia, Illinois. (3) ( 1 i i Vignentid, McKennis, Sirninonds, Dittiilcr and l3rown, J . I
