Free radical analogs of histidine

Abstract

7028nm ( E 14); nmr (Dz0) 8.55 (s, 1 H), 4.18 (t, 2 H), 3.63 (singlet methyl superimposed on multiplet, 4 H), 1.7-2.8 (m, 2 H), 1.33 (d, 3 H); tlc [Iz detection, EtOH-0.1 N HCl, 2:1] one spot, Rf 0.43; tlc [Iz detection, rz-BuOH-HOAc-HzO, 4: 1 :5] one spot, Rf 0.31 after two elutions; mass spectrum (70 eV) m/e (re1 intensity) 97 (54, M+ -HCl), 96 (loo), 82 (34). Molecular Formula: Calcdfor C6H11N(Mt -HC1): 97.0891. Found: 97.0887. 1,3,3-Trimethyl-2-pyrr0lidinone-3,3-d~mer~~l-~~C (18).To 500 ml of anhydrous diethyl ether and 220 mmole (31 ml) of diisopropylamine (freshly distilled from BaO), cooled to -70", was added 131 ml (210 mmol) of rz-butyllithium (1.6 M in hexane). Then 4.95 g (50 mmol; 4.85 ml) of 1-methyl-2-pyrrolidinone was added, the solution was stirred for 15 min at -70", and 13.8 ml (220 mmol) of CH31-*4C* was added. Stirring was continued at room temperature for 16 hr, 150 ml of HzO was added, the ether layer was removed and evaporated in DUCUO, and the residue was dissolved in 100 ml of HzO. The combined aqueous solutions were continuously extracted with methylene chloride for 24 hr. Removal of the solvent and distillation of the residue at 95-97" (27 mm) gave 4.79 g (78z) of 18: nmr (CDCl8) 3.29 (t, 2 H), 2.79 (s, 3 H), 1.81 (t, 2 H), 1.04 (s, 6 H); glpc on 30% QF-1 on Chromosorb P (168'; 100 ml/min; 10 ft X 0.25 in.) one peak, 9.0 min. Arid. ,3-dimethylpyrrolidine (17). To 6 mmol of 1,3dimethyl-1-pyrrolinium chloride and 6 ml of HzO were added 35 ml of 1 N NaOH, 10 ml of HzO, 20 ml of ethanol, and 15 ml of ethyl acetoacetate. After stirring in the dark under nitrogen for 17 days, 50 ml of concentrated HCl was added. The reaction mixture was warmed on a steam bath for 5 hr, and concentrated to 5 ml in DUCUO. The residue was dissolved in 50 ml of water and made strongly alkaline with 6 N NaOH; the resulting aqueous solution was continuously extracted with methylene chloride for 4 days. Removal of the solvent gave 440 mg (47%) of 17: ir (thin film) 1730 cm-1 ( e o ) ; nmr (CDClJ 2.7-3.7 (m, 5 H), 2.69 (s, 3 H), 1.4-2.5 (m, 3 H), 2.30 (s, 3 H), 1.12 (d, 3 H); mass spectrum (70 eV) m/e (re1 intensity ) 155 (4, MT), 140 (2), 124 (28), 109 (21), 98 (100). Warming 17 with a saturated ethanolic solution of picric acid gave the picrate which was recrystallized from absolute ethanol: mp 147-151 dec; nmr (pyridine-db) 8.97 (s, 2 H), 3.Abstract: Some stable free radical analogs of histidine have been prepared which contain a nitronyl nitroxide ring system in place of the imidazole function. The esr spectra of these amino acids show magnetically nonequivalent methylene protons as shown by different hyperfine coupling constants of the P-methylene hydrogens. The 18) T. Kawamura.

Solid‐state ESR differentiation between racemate versus enantiomer

“…After this, the nonequivalence of diastereotopic hydrogens was observed by ESR spectroscopy for several classes of radicals (e.g., simple nitroxides, 4 nitronyl nitroxides, 3,5 and nitroanion radicals 6 ). Differences of the ESR parameters of the diastereomeric nitroxide radicals bearing two stereogenic carbons on both sides of the nitroxide function were observed for the first time by Jonkman et al in 1971.…”

Syntheses of optically active 2-amino-4-oxobutyric acid and N,O-protected derivatives

“…After amino protection, oxidative cleavage was also performed using performic acid and sodium metaperiodate through a lactone alcohol interme- Table 1. Oxidative cleavage of L-allylglycine derivatives according to (Black and Wright, 1955b) (a), (Chang and Walsh, 1981) (e), (Schindler and Viola, 1994), (Giorgianni et al, 1995) (Geze et al, 1983) (Jungheim et al, 1991) (Baldwin et al, 1988a) (Agami et al, 1992(Agami et al, , 1993) (a) (f) (Tudor et al, 1993) (a) (Blickling et al, 1997) (Neuberger and Tait, 1962) (a), (Weinkam and Jorgensen, 1971) (d), (Cavrini et al, 1976) (a) (Fushiya et al, 1981a,b) (Baldwin et al, 1989a) (Itokawa et al, 1993) (a) (Szeto et al, 1995) (Stockman et al, 1996) (a) Synthesis of the aldehyde 1 is described in the experimental section. diate, apparently in low yield (Neuberger and Tait, 1962;Weinkam and Jorgensen, 1971;Cavrini et al, 1976).…”

Nitroxides. IX. Synthesis of nitroxide free radical α-amino acids

“…Relatively few data have been published on the synthesis of nitroxide free radical analogues of amino acids (6)(7)(8):…”