L-KYNURENINE SULFATE synthesis

Yield:16055-80-4 65%

Reaction Conditions:

Stage #1: (S)-4-(2-aminophenyl)-2-(((benzyloxy)carbonyl)amino)-4-oxobutanoic acidwith hydrogenchloride;palladium 10% on activated carbon;hydrogen in 1,4-dioxane;water;
Stage #2: with sulfuric acid

Steps:

(S)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid sulfate, L-Kynurenine sulfate (4)

Cbz-protected L-kynurenine (3) (3.56 g, 10.0 mmol) was dissolved/suspended in a mixture of dioxane (60 mL) and 0.5 M HCl (240 mL). 10% Pd/C (300 mg) was added and the mixture was stirred under H₂ (balloon pressure) overnight. The catalyst was then removed by filtration over celite and the filtrate concentrated under vacuum. A slight excess of 1M H₂SO₄ (12.3 mL) was then added and the solution once more concentrated under vacuum. The solid that remained was then recrystallized from 66% EtOH (250 mL) overnight at 4 oC. The precipitated product was collected by filtration and dried under vacuum to yield pure Lkynurenine sulfate as a light yellow solid (2.44 g, 65%). Analytical data: Mp: 185 oC (decomp.); ¹H NMR (D₂O): δ 8.03-8.01 (m, 1H), 7.65-7.60 (m, 1H), 7.51-7.46 (m, 1H), 7.36-7.34 (m, 1H), 4.41-4.38 (m, 1H), 3.82-3.80 (m, 1H); ¹³C NMR (DMSO-d₆): δ 199.2, 171.0, 162.3, 135.8, 132.0, 130.8, 129.3, 126.8, 125.0, 48.4, 38.9; LRMS (ESI): calcd for C₁₀H₁₃N₂O₃ [M+H]⁺ 209.09, found 209.25; [α]²⁵_D : + 9.1 (c 1.0, H₂O) [lit., [α]²⁰_D : + 9.6 (c 1.0, H₂O)].²

References:

Kleijn, Laurens H.J.;Müskens, Frederike M.;Oppedijk, Sabine F.;De Bruin, Gerjan;Martin, Nathaniel I. [Tetrahedron Letters,2012,vol. 53,# 47,p. 6430 - 6432] Location in patent:supporting information