Manuela Schäffer

An improved degradation procedure for determination of the absolute configuration in chiral isoquinoline and β-carboline derivatives☆

A reliable method for the determination of the absolute configuration of chiral isoquinolines, naphthylisoquinolines, michellamines and β-carbolines is described. The ruthenium-mediated oxidative degradation of the di- or tetra-hydropyridine heterocycle in these structures provides simple amino acid derivatives, which can be analysed by GC after Mosher-type derivatization. The method allows for the secure determination of the absolute configuration at the stereocentres C-1 or C-3 in a single step. By using a mass-selective detector instead of a flame ionization detector for GC analysis of the amino acid derivatives, the procedure offers a more sensitive detection and unambiguous characterization of the degradation products. Because of this improved method, the required stereo-information is reliably available with as little as 0.5 mg of the analysate, even for complex natural products, such as the michellamines. The broad applicability of the procedure is demonstrated by a variety of examples taken mainly from the field of natural products chemistry.

Ancistrobertsonine A and related naphthylisoquinoline alkaloids from Ancistrocladus robertsoniorum

From the as yet unexplored East African Liana, Ancistrocladus robertsoniorum, several naphthylisoquinoline alkaloids have been isolated, based mainly on High Speed Countercurrent Chromatography (HSCCC). The structure of the new compound, ancistrobertsonine A, was elucidated by chemical and spectroscopic methods. Furthermore, the known alkaloids ancistrocladine, its atropo-diastereomer, hamatine, and its regioisomer, ancistrobrevine B, were isolated.

Yaoundamines A and B, new antimalarial naphthylisoquinoline alkaloids from Ancistrocladus korupensis

Abstract New monomeric naphthylisoquinoline alkaloids, yaoundamines A and B, were isolated from Ancistrocladus korupensis and their structures were determined by extensive chemical and spectroscopic analyses. The absolute configuration at C3 was established by chemical degradation, while the axial chirality was deduced by comparison of experimental and calculated CD spectra. Yaoundamine B has an unprecedented glycosylated naphthylisoquinoline structure. Yaoundamines A and B are active in vitro against the malaria parasite Plasmodium falciparum.

Naphthylisoquinoline alkaloids from Ancistrocladus cochinchinensis

Abstract From the leaves of Ancistrocladus cochinchinensis, besides the already known ancistrocladinine, the new naturally occurring alkaloids, 6-O-methylhamateine, hamatinine, 6-O-methylhamatinine, 6-O-demethyl-7-epi-ancistrobrevine D, 7-epi- ancistrobrevine D and 6-O-demethyl-8-O-methyl-7-epi-ancistrobrevine D have been isolated and their structures elucidated from spectroscopic data and chemical degradation.

Ancistrobrevine C from Ancistrocladus abbreviatus: The first mixed ‘ancistrocladaceae/dioncophyllaceae-type’ naphthylisoquinoline alkaloid

Abstract The isolation of a new naphthylisoquinoline alkaloid, ancistrobrevine C, from the stem bark and the roots of Ancistrocladus abbreviatus is described. Its complete structure was established by spectroscopic, chiroptical and degradative methods. For additional structural confirmation, the new alkaloid was transformed into ent -ancistrocladisine, a stereochemically well known naphthylisoquinoline. Accordingly, ancistrobrevine C is neither a real Ancistrocladaceae- nor a true Dioncophyllaceae-type alkaloid, but the first mixed, hybrid-like naphthylisoquinoline alkaloid.

Dioncophylline D and 8-O-Methyldioncophylline D, 7,8′-Coupled naphthylisoquinoline alkaloids from triphyophyllum PELTATUM

Abstract Theisolation and structural elucidation of two novel naphthylisoquinoline alkaloids, dioncophylline D and its 8- O -methyl analogue, from the West African liana Triphyophyllum peltatum are described. Their structures are based on the rare 7,8′-coupling between the two molecular moieties. The absolute configuration at the stereocentres of the isoquinoline half was established by oxidative degradation to give R -3-aminobutyric acid and d -alanine. Both alkaloids are characterized by a rapid rotation around the biaryl axis. The two new alkaloids are apparently found in young (carnivorous) plants, exclusively.

Dioncophylline A, the Principal Cytotoxin from Ancistrocladus letestui

Abstract Using bioassay-guided fractionation, dioncophylline A [1] was isolated from the leaves and twigs of the tropical liana Ancistrocladus letestui Pelligr. Dioncophylline A was previously known from Triphyophyllum peltatum and A. abbreviatus. The in vitro cytotoxicity profile of 1 was characterized against the NCI panel of human tumor cell lines.

5′-O-demethyl-8-O-methyl-7-epi-dioncophylline a and its ‘regularly’ configurated atropisomer from Triphyophyllum peltatum

Abstract The isolation and structure elucidation of two new minor naphthylisoquinoline alkaloids from the stem bark of Triphyophyllum peltatum is described. From extended spectroscopic investigations, mainly NMR and CD spectroscopy, one of the alkaloids is deduced to be 5′- O -demethyl-8- O -methyl-7- epi -dioncophylline A. This new natural product is, thus, the first dioncophylline A analogous naphthylisoquinoline alkaloid from T. peltatum with an opposite configuration at the biaryl axis. Moreover, low amounts of an additional new alkaloid were isolated, whose spectral data suggest 5′- O -demethyl-8- O -methyl-dioncophylline A, i.e. the corresponding ‘normal’ atropodiastereomer.

'1R,3R)-1,3-DIMETHYL-8-HYDROXY-6-METHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE HYDROCHLORIDE: AN ENANTIOMERICALLY PURE BUILDING BLOCK FOR THE SYNTHESIS OF NA PHTHYLISOQUINOLINE ALAKALOIDS

The title compound was prepared by hydrogenolytic deprotection of the corresponding Nbenzyl derivative, which had previously been synthesized by a Picted-Spengler condensation of the corresponding arylethylamine. It crystallizes from dichloromethane/methanol in the orthorhombic system, space group P212121 ; a = 1305.7(2), b = 1400.3(3), c = 727.4(1) pm. Hydrogen bonds between Cl and OH and NH2 groups cause a threedimensional arrangement.