First Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine.

The first regio- and stereoselective total synthesis of the axially chiral 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (1) and ancistrotectorine (2) has been described. Both possess a 7,3'-coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis-array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the "lactone method": the two molecular halves, which were activated in an "inverse-halogenated" form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold.

Axially Chiral Dimeric Naphthalene and Naphthoquinone Metabolites, from Root Cultures of the West African Liana Triphyophyllum peltatum.

Root cultures of the West African liana Triphyophyllum peltatum were initiated from stem explants of in vitro cultivated shoots. From these organ cultures, three new binaphthalenes, one binaphthoquinone, and two (bi)naphthalene glucosides were isolated, with substitution patterns related to those of the naphthylisoquinoline alkaloids, which are the "normal" main metabolites of T. peltatum. The structures of the diglucoside dioncoquinoside A (1) and of the axially chiral biaryls triphyoquinols A1 (3), A2 (4), and B (5), triphyoquinoside A (6), and triphyoquinone A (7) were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and by application of electronic circular dichroism (ECD) spectroscopy in combination with the exciton chirality method and quantum-chemical ECD calculations. The root cultures likewise produced the known alkaloids dioncophylline A (8), 5'-O-demethyldioncophylline A (9), dioncopeltine A (10), habropetaline A (11), and 5'-O-methyldioncophylline D (12a/b), the naphthalene glucoside plumbaside A (2), and the naphthoquinones plumbagin (13), droserone (14), and 8-hydroxydroserone (15).

Jozimine A2: the first dimeric Dioncophyllaceae-type naphthylisoquinoline alkaloid, with three chiral axes and high antiplasmodial activity.

A new dimeric naphthylisoquinoline alkaloid, jozimine A(2) (2), was isolated from the root bark of an Ancistrocladus species from the Democratic Republic of Congo. Its absolute stereostructure was determined by chemical, spectroscopic, and chiroptical methods, and confirmed by X-ray crystallography. Jozimine A(2) (2) is one of the as yet very rare naphthylisoquinoline dimers whose central biaryl axis is rotationally hindered. Moreover, it is the first natural dimer of a Dioncophyllaceae-type alkaloid, that is, lacking oxygen functions at C6, and bearing R configurations at C3 in its two isoquinoline portions. Despite this decreased steric hindrance, the outer biaryl axes are chiral, too, so that jozimine A(2) (2) has three consecutive stereogenic axes and, together with the four stereogenic centers, seven elements of chirality and is C(2)-symmetric. The new dimer exhibits excellent, and specific, antiplasmodial activity. To further confirm its stereostructure and for likewise testing the bioactivities of its (unnatural) atropo-diastereomer, compound 2 was prepared by semi-synthesis from the co-occurring (and likewise synthetically available) dioncophylline A (5), along with its atropo-diastereomer, 3'-epi-2.