Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

2.2.3.3 Punication Met-
Once the arnino acid was deprotected, ion-exchange chromatography was used to
purify the product from the salts of the cleavage reaction. Cation purification was
generally used for the Cs2C03 based cleavages and volatile bases (5% Et3N in H D or 0.5
N NWH) employed for elution, allowing for the isolation of the free amino acid. The
solution from the Csa3 cleavage was acidified before loading ont0 the resin. Most
often, contamination resulted from incomplete hydrolysis of the rnhpd ester 2.62. Anion
exchange chrornatography effectively removed the rnhpd ester during column loading
and washing, and elution with either 0.5 N acetic or formic acid allowed the free amino
acid to be isolated. Anion exchange chromatography was most often used during
purification of the p-diallcyl-p-hydroxy amino acids in order to rninimize exposure of the
dehydration sensitive p-dialkyl-p-hydroxy moiety to basic conditions. Although strong
anion exchange resins incorporate a basic, polymer supported tetra alkylammonium
hydroxide, no racemization has been observed in previous reports from this laboratory."
Cnide yields after ionexchange chromatography varied from 40-8 1 %, however,
generally in the 50% range.
Many of the synthesized amino acids were difficult to recrystallize although
spectroscopie techniques indicated high purity after ionexchange chromatography.
Diastereomeric ratios could be determined by 'H-NMR and both diastereomeric and
enantiomeric ratios assigned after derivatization and HPLC analysis (Section 2.2.4).
Good agreement was found between the two methods.