The absolute configuration of β‐hydroxyvaline

Abstract

The optical rotatory dispersion spectra of the enantiomers of B-methoxyvaline were measured between 200 and 400 nm. From the Cotton effect at 210 nm follow the absolute configurations, and consequently those of the derived hydroxy amino acids : D-( -)-and L-( i-)-P-hydroxyvaline.P-H ydroxyvaline was formerly mentioned as a natural amino acid 1-3. This occurrence in nature was later called into question 4-7. The compound, however, remains interesting as a potential biogenetical precursor of compounds which have been derived from amino acids; these are in particular the alkaloids from ergot and the antibiotics penicillin and cephalosporin, all of them metabolic products of fungi. Cephalosporin is a research subject of this Laboratory 8 .In this connection it would seem useful to know the absolute configuration of the enantiomers of /3-hydroxyvaline. An assignment 9 exclusively on the basis of the Clough-Lutz-Jirgenson rule gives insufficient certainty. We therefore examined both optical antipodes (as 0-methyl derivatives) with the aid of optical rotatory dispersion (ORD). Our assignment of the configurations D-( -)-and L-(+)-P-hydroxyvaline is in agreement with an independent and simultaneously performed chemical correlation with D-( -)-valine 10.. . Racemic B-hydroxyvaline has repeatedly been prepared 49 9-14, We followed the route : 3,3-dimethylacrylic acid + 2-bromo-3-methoxyisovaleric acid 12 + 8-methoxyvaline *$9911. We chose this route, inter alia, because the enantiomers of the last-mentioned compound have been converted into the antipodes of /?-hydroxyvaline and the resolution of Bmethoxyvaline has already been carried out twice, viz. via the N-formyl derivative by means of brucine 15 and directly with the aid of (+)-locamphorsulfonic acid 9. The latter resolution presents a number of advantages and was applied by us with a few modifications. In the cited chemical correlation use was made of (-))-N-benzoyl-B-hydroxyvaline which had been obtained by resolution of the corresponding racemate with the aid of (-))-a-methylbenzylamine 10. S. B. SchryverIn hydroxy and amino acids the chromophore of the longest-wavelength absorption is the carboxyl group, the n +-7t* carbonyl transition of which occurs at about 220 nm. Until 1964 the ORD spectra of a-amino acids were measured no further down than to about 240 nm, and consequently only plain curves were observed. Dirkx and Sixma 16 were the first to make use of the Cotton effect around 210 nm. Similar experiments were performed by Cymerman Craig and Roy 17, and by othersl8. A positive Cotton effect around 210 nm was observed for the L-a-amino acids which have been investigated.19 (+)-p-Methoxyvaline hydrochloride shows a positive Cotton effect and accordingly belongs to the L-series; thus so does the correlated (+)-Bhydroxyvaline. The ORD of the antipode is identical with the mirror image within the limits of error and consequently shows a negative Cotton effect.