Ornithine analogs as potential ornithine decarboxylase inhibitors. 1. N-Substituted ornithine derivatives

Abstract

. Compd 5 (7 g) was added to AcOH (16.7 ml), HC1 (33.4 ml), and H30 (2.2 ml); the mixt was heated at 100°for 4 hr, then cooled, and poured into crushed ice-H30. The solid (5.8 g, 97%) was filtered and recrysted from Me3CO-petr ether: mp 133-135°; *m!$H 224 (e 4620) and 272 µ (14,200). Anal. (C14H1604) C, H. 1.2.3.4-Tetrahydro-6-methoxy-l-naphthalenepropionic Acid (7). Hydrazine hydrate (2.5 ml, 80% soln) was added to a soln of 6 (3 g) and KOH (2.7 g) in 1,2-propanediol (15 ml), the mixt was heated to 120°, and H30 was distd off. After this distillation ceased, the temperature was gradually raised to 180-190°and was maintained there under reflux for 4 hr. The reaction product was then poured into ice-H30, and acidified with HC1. The precipitated acid 7 (1.67 g, 59%) was filtered and recrystd from Me3CO: mp 122-123°;Xmax 279 <e 2150) and 288 µ (1970). Anal. (C14H1803) C, H. 4-(l,2,3,4-Tetrahydro-6-methoxy-2-naphthyl)butan-2-one (8).To a stirred soln of 7 (5 g) in anhydrous THF (70 ml) maintained at 10°under N2 was added a soln of MeLi (50 ml, 1.6 M soln in Et30), drop wise over a period of 30 min. Stirring was continued for another 1.5 hr, then excess reagent was decompd with ice H20 and the product isolated with Et20.** From the crude reaction product the ketone 8 was purified through a bisulfite addition product and was obtained as an oil (1.75 g, 35%). A 2,4-DNP deriv of 8 was prepd and recrystd from EtOH: mp 106-108°. Anal (C31H34N405) C, , N.4-(l,2,3,4-Tetrahydro-6-hydroxy-2-naphthyl)butan-2-one (9).A mixt of 8 (1.18 g) and pyridine hydrochloride (1.5 g) was heated at 205°for 1 hr under N3, then cooled, and diluted with H30. The pptd material was filtered and purified by column chromatography (alumina). The fractions eluted with PhH and PhH-Et20 (8:2) were combined to give 9 (0.48 g) which was recrystallized from Me2CO-petr ether: mp 87-89°; 280 µ (e 2180). Anal. (Cl4H1803) C, H.4-(l,2,3,4-Tetrahydro-6-hydroxy-2-naphthyl)butan-2-ol (1). To a soln of the above ketone 9 (0.262 g) in MeOH (20 ml) was added NaBH" (0.145 g), and the soln was stirred at room temp

Polyamine biosynthesis in rat prostate. Substrate and inhibitor properties of 7-deaza analogs of decarboxylated S-adenosylmethionine and 5'-methylthioadenosine

“…As an initial step in establishing the ability of tubercidin to form 9b via this pathway, we chose to study the reaction catalyzed by spermidine synthase. This enzyme catalyzes the transfer of a propylamino group from 7a to putrescine (8). The products of the reaction are the polyamine spermidine (10) and 9a.…”

“…When the concentration of 7a was varied (0.01-1.0 mM), while maintaining a constant, high concentration (1 mM) of putrescine, a marked substrate inhibition was observed (Figure2). When the concentration of the second substrate, putrescine(8), was varied (0.1-2.0 mM), while…”

Analogs of ornithine as inhibitors of ornithine decarboxylase. New deductions concerning the topography of the enzyme's active site

“…The residue was dissolved in absolute ethanol (180 mL) and the pH of the solution was adjusted to 4 by adding a solution of triethylamine in ethanol (1 M) (56 mL). The solid which formed was collected by filtration, washed with ethanol, and recrystallized (H20-EtOH) to yield 10.4 g (87%) -78 °C was added slowly under nitrogen a solution of methylbenzaldimine alanate (29) (1.91 g, 0.01 mol) in anhydrous THF.…”

Oxidative DNA cleavage, cytotoxicity and antimicrobial studies of l-ornithine copper (II) complexes

“…L-Ornithine is a non-protein, basic amino acid and it is most potent for stimulating, production and release of growth hormones, in maintaining arterial flexibility and defeating hypertension [40][41][42]. Ornithine decarboxylase activity is higher in rapidly growing tumors than in non-malignant tumors [43][44][45]. This activity may be reduced by chelating the carboxylate group of ornithine.…”