3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid → Methyl alpha-methyl-D-tryptophanate

Beteiligte Stoffe

Reaktionsschritte

To a suspension of (±)-α-methyltryptophan methyl ester (102.8 mg, 0.443 mmol) in 25 mL of 50 mM sodium phosphate buffer pH 6.0 was added carboxypeptidase P from Penicillium janthinellum (3.2 rag of protein). The resulting suspension was stirred at ambient temperature. After 2 h, 50% conversion was observed by HPLC (C18 column, 254 nm detection, acid tR =9.0 min and ester tR =11.9 min). The reaction was adjusted to pH 10 by the addition of 2N KOH and then was extracted with 3×25 mL ethyl acetate. The combined extracts were treated with brine, dried with magnesium sulfate, then concentrated in vacuo to yield (R)-α-methyltryptophan methyl ester (40 mg, 172 mmol, 38.8%): 1H NMR (400 MHz, CDCl3 -THS) δ8.34 (bs, 1H) , 7.61 (d, 7.9 Hz, 1H) , 7.30 (d, 8.54 Hz, 1H) , 7.16 (dd, 7.0, 7.0 Hz, 1H) , 7.10 (dd, 7.6, 7.6 Hz, 1H), 6.98 {s, 1H) , 3.64 (s, 3H), 3.29 (A of AB, JAB=14.6 Hz, 1H), 3.01 (B of AB, JAB=14.6 Hz, 1H) , 1.92 (bs, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ177.85, 135.99, 128.08, 123.30, 121.91, 119.44, 119.09, 111. 07, 110.65, 59.14, 52.09, 36.38, 26.61. A portion of this (R)-α-methyl amino ester (1.6 mg, 6.89 mmol) was refluxed in 20 mL 6N HCl for 2 h then concentrated in vacuo to afford (R)-α-methyltryptophan hydrochloride (1.6 mg, 6.28 mmol, 91.1%). The enantiomeric excess of the amino acid was determined by HPLC analysis ((D)-Penicillinamine column from Phenomonex, detection 254 nm, (R)-enantiomer tR =12.4 min and (S)-enantiomer tR =14.6 min) to be >99% (R)-enantiomer.

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