Author Topic: Translations of Articles Wanted  (Read 13666 times)

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java

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Transalte the theory.....
« Reply #40 on: July 05, 2004, 04:09:00 AM »
armageddon

The rxn mechanism/theoretical part would be nice  to understand the mechanism....thankx..java


armageddon

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Synthesis of N-monomethylamino acids translated
« Reply #41 on: July 12, 2004, 03:47:00 AM »
32. The synthesis of optically active N-monomethyl-amino-acids (1)

by P. Quitt, J. Hellerbach and K. Vogler (bumpy english by armageddon)
(7.XII.62)

During the last years, several naturally occuring peptide- and depsipeptide-antibiotics (containing unusual amino acids as building blocks) were discovered. Of these, the N-monomethylamino acids seem to have widespread occurence. For example, N-methyl-L-isoleucin was found in enniatin A (2), N-methyl-L-valin in enniatin B (2) and in actinomycins (3), N-methyl-L-leucin in sporidesmolid I (4), N,beta-dimethyl-L-leucin in Etamycin (3), N-methyl-L-phenylalanin and p-dimethylamino-N-methyl-L-phenylalanin in staphylomycin (6) or ostreogrycin (7) and finally N-methyl-L-phenylglycin in etamycin (5). Both actinomycin and etamycin contain also sarcosin.

Although the preparation of optically inactive or racemic methylamino acids doesn't present any problems, there is currently no satisfying synthesis of optically active methylamino acids. The common method consists in methylation of the tosyl derivatives, followed by cleavage of the tosyl group with sodium in ammonia or boiling hydrochloric acid.

This procedure, developed by FISCHER(8), usually gives partially racemized products (9), so that intermediate products have to be purified via salt formation with optically acitve bases (10). Especially during the methylation with dimethylsulfate or methyliodide (if it is desired to occur in good yield), significant racemization occurs. A tedious separation of the end products is necessary/highly recommended. Also invented by FISCHER(11) but later applied by COOK et al. (9) was the method of replacing bromine with methylamine on optically active alpha-bromo-fatty acids. But even when this method is used, the obtained products were strongly racemized, as we were able to confirm with own experiments.

In contrast to these, the reductive alkylation as performed by BOWMAN(12) on different amino acids using different aldehydes, proceeds without racemization. Although with higher aldehydes, only monoalkyl derivatives are obtained, the use of formaldehyde always results in dimethyl derivative formation(13) or - when only one equivalent of formaldehyde is used - a mixture of mono-, di- and unmethylated products, whereas the desired derivative is obtained only in 5-25% yield and its separation from side products is often very difficult to accomplish (14).

{it follows the reaction scheme:
"Benzaldehyd" is benzaldehyde - obvious...
"oder" means "or"..
"Eisessig" is GAA... (everything else should be self-explaining)}

Moreover, certain N-methylamino acids were made from actinomycines (15). The method described here dips into the principle of reductive alkylation by using benzaldehyde as the aldehyde compound (16). Like shown in the reaction scheme, this leads to a benzyl compound III, which can then be selectively monomethylated. The benzyl-methylamino acid IV, after hydrogenolytic debenzylation, finally gives the desired N-monomethylamino acid V. The benzylidene compounds of the amino acids II are only stable in their salt form and were first isolated by BERGMANN et al.(17) and later by WIELAND & SCHAEFER(18). They don't tend to racemize, a fact which was already observed before by GULLAND & MEAD(19) and by TAGUCHI & ISHIDA(20). Newly, benzaldehyde was also used to protect the epsilon-amino group of lysin (21), as it is easily spit off hydrolytically in acidic solutions.

Compound II isn't isolated, but reduced to the N-benzyl compound III in situ, either catalytically or with sodium borohydride. The isolation of N-benzyl amino acids is accomplished very easily because of their poor solubility (in water) at the isoelectric point {whatever this means!!}. The methylation of the benzyl compound III is done according to the method of LEUCKART & WALLACH (22). This method generally leads straight to the N-benzyl-N-methyl derivative IV which can be isolated - meanwhile, With basic and hydroxyl containing amino acids, side reactions are likely to occur. For example, partial decarbobenzoxylation occurs when N-carbobenzoxy-N-benzyl-L-lysin is treated with hot formic acid, which can lead to partial methylation of the epsilon-amino group. Therefore it is therefore necessary that minimal reaction times are met and that isolation of compound  IV isn't attempted. The same applies to the nitroarginin- and the serin derivative, as changes of unknown nature can happen to them as a result of too long reaction times. The kind of methylation procedure implies that after hydrogenolytic debenzylation has occured, the monomethylamino acid V appears in its salt-free form, even if compound IV cannot be isolated. In this last stage, it has to be considered that more hydrogenolysable protection groups can be removed from the molecule if present (Va, Vb). This involves for example the nitroarginin- and the N-carbobenzoxylysin derivative, with which unprotected methylamino acids are obtained without using sodium in liquid ammonia, contrasted to the N-tosyl derivative.

The specific rotations of the starting compounds, intermediates and end products are summarized in the table.

{table}



EXPERIMENTAL PART
1. N-benzyl-L-amino acids - Method A: 0.1 mol of the amino acid are dissolved in 50ml 2n NaOH soln. and 10.1ml (0.1 mol) freshly distilled benzaldehyde are added with good stirring. After 15-20 minutes, the solution has become homogenous. Then, 1.14g (0.03 mol) NaBH4 are added in small portions (alternatively, an aequous solution thereof is added dropwise). The temperature shouldn't exceed 15°C when doing this. After addition is finished, stirring is continued for 1/2 hour, and the procedure is repeated with fresh benzaldehyde and sodium borohydride. Stirring is then continued for 2 more hours before the mixture is washed 2x with ether and brought to pH 6-7 with 1n HCl with good stirring. The benzylamino acid usually precipitates rather quickly and is vacuum filtered, washed thoroughly with water and dried under vacuum. It is usually pure enough for the further reaction steps.





I put my comments into {braces} - I am not sure about the funky amino acid names, so I left them untouched....

Hope my translation is useful to you, java...

Greetz A