Hélène Guinaudeau

The protoberberine alkaloids of Stephania suberosa

Abstract Six new protoberberines were found in Stephama suberosa root extracts: (−)-tetrahydrostephabine, (−)-stephabinamine, stephabine, 8-oxypseudopalmatine, (−)- trans -xylopinine N -oxide and (−)- cis -xylopinine N -oxide. Ten known alkaloids were also detected: (−)-tetrahydropalmatine, (−)-tetrahydropalmatrubine, (−)-stepholidine, (−)-kikemanine, (−)-capaurimine, (−)-coreximine, (−)-corytenchine, (−)-discretine, pseudopalmatine and (−)-xylopinine.

Trypanocidal Bisbenzylisoquinoline Alkaloids are Inhibitors of Trypanothione Reductase

Eleven bisbenzylisoquinoline (BBIQ) alkaloids were studied for in vitro trypanocidal activity against trypomastigote forms of the Y strain of Trypanosoma cruzi. The inhibitory activity of these compounds against trypanothione reductase (TR), a target enzyme for chemotherapy against Chagas disease, was also studied. Six BBIQ alkaloids (antioquine, cepharanthine, daphnoline, limacine, cycleanine and (-) curine) displayed a 50% lethal concentration (LC50) against T. cruzi of less than 100 microM. Daphnoline and curine, with LC50 values of 10 microM, are attractive for further investigation as potential anti-Chagasic drugs. Kinetic analyses suggested the BBIQ alkaloids are mixed inhibitors of TR. These compounds are reasonably potent inhibitors of TR; the best TR inhibitor, cepharanthine, had an IC50 of 15 microM, which is in the same order of magnitude as its LC50 against T. cruzi. The similar magnitudes of the IC50 and LC50 values suggest that inhibition of TR could contribute to the trypanocidal activity exhibited by the BBIQ alkaloids.

Faralatroside and faratroside, two flavonol triglycosides from Colubrina faralaotra

Abstract Two new flavonol triosides have been isolated from the leaves of Colubrina faralaotra (Rhamnaceae) and their structures elucidated as kaempferol-3- O -[β- d -glucopyranosyl-(1 → 3)-4″′- O -acetyl-α- l -rhamnopyranosyl-(1 → 6)-β- d -galactopyranoside] and the corresponding quercetin analogue mainly by 1 H and 13 C NMR spectroscopy (including T 1 , measurements).

The effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice

Five bisbenzylisoquinoline (BBI) alkaloids, curine, cycleanine, isotet:andrine, limacine and pheanthine were tested for trypanocidal activity in C 3H He mice infected with Y or CL strain of Trypanosoma cruzi. The activity was compared with the baseline drug, benznidazole. Oral treatment was more effective with curine at 10 mg/kg or with cycleanine at 2 mg/kg daily for 10 days in mice infected with Y or CL strain. In these groups, the parasitemias were negative after 5-7 weeks after inoculation and mortality time 50 (MT(50)) was significantly higher than untreated mice. Benznidazole was effective in mice infected with CL strain but not in mice infected with Y strain. The other BBI showed a relative efficacy against both strains. The effect of BBI alkaloids could be due to a blocking of the Ca2+ channel for the regulation of T. cruzi infectivity to invade host cells or their selective immunosuppressive properties.

Essential Oils from Zanthoxylum chiloperone and Z. riedelianum Growing in Paraguay

Essential oils from aerial parts of Zanthoxylum chiloperone var. angustifolium Engl. and Z. riedelianum Engl. have been analyzed by GC/MS. Twenty-four compounds were identified, representing 80% of essential oils. The main components of these essential oils are, respectively, cis -nerolidol (71.0%) and spathulenol (65.2%).

A new subgroup of bisbenzylisoquinoline alkaloids: (+)-cycleatjehenine and (+)-cycleatjehine

The leaves of Cyclea atjehensis Forman (Menispermaceae) of Thai origin have yielded the bisbenzylisoquinolines (+)-cycleatjehenine(1a) and (+)-cycleatjehine(6) . These alkaloids incorporate the unusual methyleneoxy bridge, and belong to a new bisbenzylisoquinoline subgroup.

New proaporphine alkaloids from roemeria hybrida

Abstract Roemeria hybrida (L.) DC. (Papaveraceae) of Turkish origin has yielded the new prosporphine alkaloids (-)-roemerialinone ( 3 ), (-)-isoorientalinone ( 4 ), (-)-isoroemerialinone ( 5 ), (-)- 11,12-dihydroorientalinone ( 6 ), (+)-8, 9-dihydroisoroemerialinone ( 9 ) and (-)-α-roemehybrine ( 11 ). Catalytic reduction of (-)-isoorientalinone ( 4 ) led to (+)-8, 9-dihydroisoorientalinone ( 8 ) which corresponds to the partly characterized “(+)-dihydroorientalinone” originally obtained from Papaver orientale . The previously known (-)-roehybrine ( 10 ) of undetermined structure was also reisolated, and its structure was elucidated. Known proaporphines present are (-)-mecambrine ( 1 ) and (-)-orientalinone ( 2 ). The isolation of such pairs of diastereomeric proaporphines as 2 and 4 , and 3 and 5 , points to the fact that enzyme catalyzed intramolecular oxidative coupling of a specific tetraoxygenated tetrahydrobenzylisoquinoline may occur in either of two modes, depending upon the folding of the pendant benzylic ring.

The stereochemistry of reduced proaporphines

Abstract Controlled catalytic hydrogenation of the proaporphine (+)-stepharine ( 1 ) proceeded by preferential approach of the catalyst from the side opposite H-6a to provide (+)-8,9-dihydrostepharine ( 3 ), accompanied by smaller amounts of (-)-11,12-dihydrostepharine ( 4 ) and (+)-tetrahydrostepharine ( 5 ). NaBH 4 reduction of 5 led to (+)-α- and (+)- β-hexahydrostepharine ( 6 and 7 ). Complete spectral and optical data were obtained for all reduction products, thus supplying reliable standards for the characterization of reduced proaporphine alkaloids.

Importance of steric factors in the conversion of proaporphines into aporphines. Stereochemistry of the dienone–phenol and dienol–benzene rearrangements

Proaporphines belongong to the C-6a-(R) configuration will undergo counter-clockwise rotation of the dienone system during their acid-catalysed rearrangement to aporphines, while proaporphines of the (S) configuration will suffer a corresponding clockwise rotation; the aryl ring thus migrates from the C-13 spiro-centre to that carbon of the dienone which is syn to 6a-H.

Coyhaiquine: an oxidized proaporphine–benzylisoquinoline alkaloid

The study of the n.m.r. spectrum of (+)-coyhaiquine (1), the first known oxidized proaporphine–benzylisoquinoline, has led to a simple method for the assignment of stereochemistry at C-13 for the proaporphines.