Brucine N-oxide

The virtue of performing the PKR in an enantioselective manner has been extensively elaborated during the last decade. As a result, different powerful procedures were developed, spanning both auxiliary-based approaches and catalytic asymmetric reactions. For instance, the use of chiral N-oxides was reported by Kerr et al., who examined the effect of the chiral brucine N-oxide in the intermolecular PKR of propargylic alcohols and norbornadiene [59]. Under optimized conditions, ee values up to 78% at - 60 °C have been obtained (Eq. 10). Chiral sparteine N-oxides are also able to induce chirality, but the observed enantioselectivity was comparatively lower [60]. 

Tab. 14.3 Chemical shift assignments for strychnine (1), brucine (51), holstiine (52), strychnine N-oxide (54), and brucine N-oxide (55) in deuterochloroform.

Two pieces of chemical evidence support the three-membered ring formulation. The bifunctional oxazirane prepared from glyoxal, tert-butylamine, and peracetic acid (6) can be obtained in two crystalline isomeric forms. According to the three-membered ring formula there should be two asymmetric carbon atoms which should allow the existence of meso and racemic forms. A partial optical resolution was carried out with 2-7i-propyl-3-methyl-3-isobutyloxazirane. Brucine was oxidized to the N-oxide with excess of the oxazirane. It was found that the unused oxazirane was optically active. 

However, as investigation progressed, ethnobotanical and pharmacological works have revealed that alkaloids of Strychnos species display a broad spectrum of biological activities [3, 4]. This has attracted the interests of phytochemists over the last three decades as evidenced by the continued publication of several review articles devoted to this series of alkaloids [5, 6, 7]. While 150 years were necessary to completely elucidate the structure of 1, structure determination has considerably benefited from the progress of NMR techniques, especially H- H and 2D-NMR experiments. Based on their particular structures, the Strychnos alkaloids have been the focal point of considerable spectroscopic efforts. More recently some selected Strychnos alkaloids, 1 and brucine (2), and their N-oxide derivatives, have been used successfully as model compounds for the application of the 15N NMR methods [8, 9]. 

Wieland s Cn-acid has been derived from brucine by an alternate method. Brucine is oxidized by cold 5 N nitric acid to a quinone, bisdesmethylbrucine (bruciquinone) (C21H20O4N2) (XXX) (159), and by warm nitric acid to cacotheline (the nitrate of nitrobruciquinone hydrate)... 

Groups of reportedly photochromic systems which deserve further study include (a) disulfoxides (123,124), (b) hydrazones (125-129), (c) osazones (130-133), (d ) semicarbazones (134-143), (e) stilbene derivatives (144), (/) succinic anhydrides (145-148), and (g) various dyes (149,150). A number of individual compounds also remain unclassified as to their mechanism of photochromic activity. These include o-nitro-benzylidine isonicotinic acid hydrazide (151), 2,3-epoxy-2-ethyl-3-phenyl-1-indanone (152), p-diethyl- and p-dimethyl-aminophenyli-minocamphor (153), brucine salts of bromo- and chloro-nitromethionic acid (154), diphenacyldiphenylmethane (155,156), 2,4,4,6-tetraphenyl-1,4,-dihydropyridine (155,156), 2,4,4,6-3,5-dibenzoyltetrahydropyran (155,156), o-nitrobenzylidenedesoxybenzoin (157), p-nitrobenzylidene-desoxybenzoin (157), N-(3-pyridyl)sydnone (158,159), tetrabenzoyl-ethylene (160), and the oxidation product of 2,4,5-triphenylimidazole (161,162). 

Nitrate is reduced to nitrite (by cadmium reduction reaction), which is then determined by diazotization (pH = 2.0-2.5) with sulfanilamide and coupling N-( 1 -naphthyl)-1,2-ethylendiamine hydrochloride to form an intensely pink colored azo dye (540 nm) Brucine oxidation by nitrate ion in H2S04 at 100°C to form a yellow compound (cacoteline), which is measured at 410 nm... 

In practically all the instances of its use, attack of a double bond and of C-20 (between Nb and the C-21 to C-22 double bond) occurs. There is no instance of the simple oxidative disruption of a benzene nucleus indeed, the most vigorous conditions, aqueous alkaline permanganate at 50°-70°, lead to the oxidation of strychnine to N-oxalylanthranilic acid in about 8% yield. Brucine likewise gives 4,5-dimethoxy-iV-oxalyl-anthranilic acid, but in much lower yield (0.1 to 0.2%) (18). a-Colubrine (3-methoxystrychnine) gave a 2.7% yield of 4-methoxy- and /J-colubrine (2-methoxystrychnine) a 5.5% yield of 5-methoxy-iV-oxalylanthranilic acid (125). These oxidations fixed the positions of the methoxyl groups in the last three alkaloids. 

The aldonic acids of the pentose series were prepared similarly. L-Arabonic acid was isolated by Kiliani as the calcium salt, and Ruff prepared calcium n-arabonate. In the latter case almost quantitative yields were reported. n-Lyxonic acid was isolated as the basic lead salt and converted to the crystalline lactone by Wohl and List. n-Ribose was oxidized to the crystalline cadmium n-ribonate by Levene and Jacobs the yield was less than 50%. The well-known boat-shaped crystals of the double salt of cadmium n-xylonate-cadmium bromide were prepared by the oxidation of n-xylose with an excess of bromine by Ruff, followed by a subsequent treatment with cadmium carbonate. Ruff also prepared L-erythronic acid, isolating it as the brucine salt the starting material was a crude n-erythrose sirup prepared by degradation of calcium L-arabonate. 

Another method of preparing keto aldonic acids, those of the 2-keto type, is by oxidation of the corresponding osone. Neuberg and Kitasato obtained 18 g. of calcium 2-keto-D-gluconate from 20 g. of the osone by the action of bromine at 20 . Similarly, 2-keto-n-galactonic and 2-keto-maltobionic acids were prepared by Kitasato. The substances were characterized generally as the brucine salts because of the amorphous nature of the calcium salts. 

Bergmann and Wolff S reported a small yield (1 g.) of menthol a-D-glucuronide by the oxidation of 12 g. of menthol a-n-glucoside in pyridine solution with sodium hypobromite. Better yields were obtained by Smolenski, who oxidized methyl a-n-glucopyranoside with bromine and sodium carbonate a 30% yield of the methyl n-glucuronide (as the brucine salt) was reported. Jackson and Hudson obtained a 12% yield of the brucine salt of methyl a-n-mannuronide by the barium hypobromite oxidation of methyl a-n-mannopyranoside. 

Ingles heated a solution of n-glucose, sodium sulfite, and bisulfite, removed the cations, and steam-distilled the residue. The product, free of carbonyl-bisulfite addition compounds, was chromatographed on an ion-exchange resin, giving a sulfonic acid. This acid yields a crystalline brucine salt and phenyl- and (2,4-dinitrophenyl)-osazones. The osazones consume 1 mole of periodate per mole, liberating 1 mole of formaldehyde but no formic acid. The (2,4-dinitrophenyl)osazone also forms a diacetate. The acid is oxidized by sodium hypoiodite, taking up 1 mole of oxidant per mole. From these reactions and the possible reaction mechanisms for its formation, structure (41), a 3,4-dideoxy-4-sulfo-n-hexosulose, was proposed for the sulfonic acid. ... 

Phillipson, J. D. and Bisset, N. G. (1972) Quatemisation and oxidation of strychnine and brucine during plant extraction. Phytochemistry 11,2547—2553. 

---