Z-Trp-Trp-OH

Chemical Properties

White to off-white powder

Synthesis

Cbz-tryptophanyl-tryptophan was synthesized from the compound (CAS: 17689-58-6) using the saponification method of McDermott et al. (Journal of the American Chemical Society 1982, 104, 3002-3007). The procedure is as follows: the di-protected dipeptide (0.425 g, 0.79 mmol) is dissolved in methanol (20 mL), followed by the addition of 1N NaOH (5 mL) to the solution. The reaction scale could be expanded to twofold or threefold as required without affecting the progress of the reaction. The progress of the reaction was monitored by TLC during the reaction. After 2 hours of reaction, water (20 mL) was added and washed with ether (2 x 20 mL) to remove unreacted material. Subsequently, the aqueous layer was acidified with concentrated hydrochloric acid to pH 2. Hydrochloric acid and ethyl acetate (20 mL) were added rapidly to separate the ethyl acetate layer, and the aqueous layer was then extracted with two parts of ethyl acetate (20 mL). The organic phases were combined, dried over magnesium sulfate and concentrated, and the resulting oil was recrystallized by ethyl acetate/hexane and subsequently recrystallized again from methanol/water. The final white solid obtained was dried under vacuum. The product was Cbz-Trp-Trp-OH (Cbz-L-Trp-L-Trp-OH) as a white solid (0.257 g, 87.3% yield) with a melting point of 207-210 °C (literature value 209-210 °C) and [α]D25 +19.2 (c 0.8 in acetic acid; literature value +23.7, c 0.8 in acetic acid).TLC analysis showed Rf values A: 0.74, B: 0.69. IR spectrum (vmax) showed characteristic absorption peaks: 3412 (NH), 3372 (NH), 3334 (NH), 3054 (aromatic CH), 2921 (CH), 1729 (COOH), 1695 (C=O), 1659 (C=O), 1515 (aromatic C=C) cm -1. Nuclear magnetic resonance hydrogen (1H NMR) and carbon (13C NMR) spectral data were consistent with the structure. The mass spectrum (FAB) showed the molecular ion peak m/z: 525.2 [M+H]+.

References

[1] Patent: WO2006/125324, 2006, A1. Location in patent: Page/Page column 128-129
[2] Tetrahedron Letters, 1982, vol. 23, # 19, p. 1985 - 1988