Tryptophans enantiomeric purity

Since tryptophan synthase does not (or poorly) tolerate the substitution of indoles by large groups (iodo- and nitro-groups), such cases have lead to the development of a facial chemical synthesis of racemic A-oc-acetyltryptophan derivatives from 5- and 6-monosubstituted indoles and L-serine, followed by an enzymatic resolution step using acylase Amano resulting in substituted L-tryptophans in high yields and enantiomeric purity of 91-100% ee [66] (Fig. 4). 

Limits of detection for many amino acids were enhanced considerably by pre-column derivatization with the achiral reagent dansyl chloride whose function it was to increase their specific rotation [17]. Determinations of the enantiomeric purities for mixtures of D-and L-tryptophan [18] and of isomeric ratios for mixtures of pseudoephedrine and its diastereomer ephedrine [19], were effected using diode-laser polarimetry and using OR detection in series with UV absorbance detection respectively. 

A recent report (41) has highlighted the usefulness of CE to determine the enantiomeric purity of individuals coming from parallel synthesis, either during chemical assessment to help revising the experimental protocols and as a library QC tool to determine the stereochemical quality and purity of chiral libraries. The authors studied the Pictet-Spengler reaction of chiral tryptophans with carbonyl compounds on SP to provide tetrahydro-P-carbolines, and clearly highlighted the reaction conditions-dependent racemization of the reaction products. 

Cook and co-workers (212) have developed a strategy that permits an enantiospecific synthesis of compound 126. A b-Benzyl D-(+)-tryptophan methyl ester (127) was transformed with methyl 4,4-dimethoxybutyrate (or methyl y-aldobutyrate) to the trans diester 128, which, after 60 hours reflux (NaH/MeOH/toluene) led, via epimerization and Dieckmann condensation, to the /3-ketoester 129 (enantiomeric purity s 98%). Acid-induced decarboxylation of the /3-ketoester 129 afforded the desired compound 126... 

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