Preparação de aminoacidos não proteinogenicos, estruturalmente relacionados ao adoçante natural Monatina

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

Monatin is a natural amino acid, which exhibits sweetener potency 1400 times bigger than glucose. When mixtured with other sweeteners this compound increases the taste and the flavor of some preparation. This feature increases the biological and commercial importance of Monatin. This amino acid has been isolated from the roots of the south African plant Schlerochiton illicifolius and could be seen as the combination of two amino acid residues: glutamic acid and triptofan. In the literature there are no systematic study describing the relationship between the structure and the biological activity of Monatin derivatives. This fact increases the interest in Monatin as a potential prototype for the development of a new class of artificial sweetener. In this work we describe our results focused on the evaluation of the efficiency of two new different strategies for the preparation of Monatin derivatives. One which started with pyroglutamic acid (1) and the other using 4-hydroxyproline as substrate (1a). The strategies were started with compounds 1 and 1a. In the first strategy we decided to use a methodology already available in our laboratory and developed by us. The methodology based on the utilization of 4-hydroxyproline (1a) was established during the development of this work. Then, the oxidation of 1, in position 4 was accomplished with a chemical yield of 53%, using dibenzyl dicarbonate peroxide as oxidizing agent. The alkylation reaction of a derivative of 1 led to preparation of several Monatin derivatives with a chemical yield of 10-40%. In order to increase the chemical yield of the oxidation and alkylation steps of 1, several modifications were tested. Unfortunately, we are unable to obtain better results. When 4-hydroxyproline was used as substrate we observed an increasing in the global yield of the strategy. Depending on the electrophile used it was possible to observe a good level of diastereoselectivity in the alkylation step for the both substrates employed. The degree of diastereoselection observed varied from 55:45 to 95:5. Apparently, the diastereoselectivity observed has a direct relationship with the size of electrophile. The relative stereochemistry of the alkylated derivatives (obtained from pyroglutamic acid and from 4-hydroxyproline) was readily determined through differential nOe experiments. The alkylated products 8a, 9a and 10a were then treated with concentrated HCl in order to remove the protecting groups (OTBS and Boc) and hydrolyse the ester function of these compounds. This sequence led to the preparation of compounds 14a, 15a and 16a, however the chemical yields obtained were very low (10-15%). Hydrolysis of the lactam core will afford the Monatin derivatives (17a, 18a and 19a). Later, these compounds will be biologically evaluated.

ASSUNTO(S)

testes quimicos e reagentes adoçantes artificiais

ACESSO AO ARTIGO

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