| Identification | Back Directory | [Name]
6-CHLORO-L-TRYPTOPHAN | [CAS]
33468-35-8 | [Synonyms]
L-6-CHLOROTRYPTOPHAN
6-CHLORO-L-TRYPTOPHAN
L-Tryptophan, 6-chloro-
6-Chloro-(s)-Tryptophan
6-Chloro-L-tryptophane
-2-Amino-3-(6-chloro-1H-indol-3-yl)
(S)-2-AMino-3-(6-chloro-1H-indol-3-yl)propanoic acid
(2S)-2-amino-3-(6-chloro-1H-indol-3-yl)propanoic acid | [Molecular Formula]
C11H11ClN2O2 | [MDL Number]
MFCD02683925 | [MOL File]
33468-35-8.mol | [Molecular Weight]
238.67 |
| Chemical Properties | Back Directory | [Appearance]
Colourless Prisms | [Melting point ]
244-246°C | [Boiling point ]
476.9±45.0 °C(Predicted) | [density ]
1.474±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
Aqueous Acid (Slightly), Methanol (Very Slightly, Heated) | [form ]
Solid | [pka]
2.22±0.10(Predicted) | [color ]
Off-White to Pale Beige | [InChI]
InChI=1S/C11H11ClN2O2/c12-7-1-2-8-6(3-9(13)11(15)16)5-14-10(8)4-7/h1-2,4-5,9,14H,3,13H2,(H,15,16)/t9-/m0/s1 | [InChIKey]
FICLVQOYKYBXFN-VIFPVBQESA-N | [SMILES]
C(O)(=O)[C@H](CC1C2=C(C=C(Cl)C=C2)NC=1)N | [CAS DataBase Reference]
33468-35-8 |
| Hazard Information | Back Directory | [Chemical Properties]
Colourless Prisms | [Uses]
The natural enantiomer of Chlorotryptophan | [Definition]
ChEBI:6-chloro-L-tryptophan is a non-proteinogenic L-alpha-amino acid that is L-tryptophan in which the hydrogen at position 6 on the indole ring has been replaced by a chlorine. It is a non-proteinogenic L-alpha-amino acid, a L-tryptophan derivative and an organochlorine compound. It is a tautomer of a 6-chloro-L-tryptophan zwitterion. | [Synthesis]
The general procedure for the synthesis of (S)-2-amino-3-(6-chloro-1H-indol-3-yl)propionic acid from AC-DL-6-chlorotryptophan was as follows:
1. 6-Chloroindole (500 mg, 3.31 mmol, 1 eq.) and L-serine (695 mg, 6.62 mmol, 2 eq.) were dissolved in acetic acid (10 mL) and acetic anhydride (3.1 mL, 33.1 mmol, 10 eq.) was added. The mixture was stirred at 73 °C for 4 hours under argon protection. Upon completion of the reaction, the mixture was concentrated to half the original volume, diluted with water and extracted with ethyl acetate (EtOAc). The organic layers were combined, dried over sodium sulfate and evaporated to give the crude product N-acetyl-6-chloro-D,L-tryptophan (686 mg, 74% yield).
2. N-Acetyl-6-chloro-D,L-tryptophan (686 mg, 1.45 mmol) was dissolved in pH 8.0 phosphate buffer (50 mL) containing 1 mM CoCl2-6H2O. Acylase I (500 mg) was added and stirred at 37 °C for 24 h, during which time the pH was adjusted with LiOH to 8.0. Upon completion of the reaction, the mixture was heated to 60 °C and kept at 60 °C for 5 min, cooled to room temperature and then filtered through diatomaceous earth. The filtrate was acidified with HCl to pH about 3 and extracted with EtOAc. The aqueous layer was lyophilized and used as crude product for the next reaction (estimated yield 43%, based on the theoretical yield of L-enantiomer, 125.4 mg).
3. 6-Chloro-L-tryptophan (125.4 mg, 0.527 mmol, 1 eq.) was dissolved in a water/acetone (1:1, v/v) solvent mixture and NaHCO3 (88.5 mg, 1.05 mmol, 2 eq.) was added. Fmoc-OSu (195.6 mg, 0.58 mmol, 1.1 eq.) was dissolved in acetone and added to the reaction mixture in batches over 3 hours. After completion of the reaction, the acetone was evaporated and the aqueous layer was acidified with acetic acid to pH about 3 and extracted with EtOAc. The organic layers were combined, dried over sodium sulfate and evaporated. The crude product was purified by fast column chromatography (eluent: hexane:EtOAc:AcOH = 10:9:1) to give pure Fmoc-6-chloro-L-tryptophan (237 mg, 98% yield). | [References]
[1] Patent: WO2015/153761, 2015, A2. Location in patent: Paragraph 00256 |
|
|