5′-O-Methyldioncophylline D, a 7,8′-coupled naphthylisoquinoline alkaloid from callus cultures of Triphyophyllum peltatum, and its biosynthesis from a late-stage tetrahydroisoquinoline precursor

Ealamines A–H, a Series of Naphthylisoquinolines with the Rare 7,8′-Coupling Site, from the Congolese Liana Ancistrocladus ealaensis, Targeting Pancreatic Cancer Cells

“…Again, the half-chair conformation was not predominant. This corroborated that such a previously unrecognized conformational preference of the tetrahydro­isoquinoline portion, with both the nitrogen atom and C-3 “down”, was linked to the spatial orientation of the two chromophores within the series of so far quite rare M -configured 7,8′-coupled naphthyl­isoquinoline alkaloids. ,, The new alkaloid thus possessed the full stereostructure 5 (Figure ) and was named ealamine C.…”

“…Naphthylisoquinoline alkaloids − are the only di- and tetrahydroisoquinoline natural products that are not, as usual, built up from aromatic amino acids, but from acetate/malonate units, following a novel, polyketidic pathway to isoquinolines in plants . Their two molecular halves, the naphthalene and the isoquinoline subunits, are formed separately, both from joint polyketide precursors, and are connected to each other at a quite late stage of the biosynthetic route, ,, by phenol-oxidative cross-coupling, which occurs ortho or para relative to free phenolic oxygen functions. Based on this principle, eight C , C-coupling types are imaginable, of which seven (viz., 5,1′, 5,3′, 5,8′, 7,1′, 7,3′, 7,6′, and 7,8′) have so far been discovered in Nature. − …”

“…The elucidation of the axial configuration of the new hybrid-type 7,8′-coupled naphthyl­tetrahydroisoquinolines with R -configuration at C-3 by 2D NMR measurements proved to be unexpectedly challenging, since the energetically preferred conformers of the tetrahydropyrido parts of the M -configured alkaloids ealamines B ( 4b ) and C ( 5 ) were found to adopt an arrangement with both the nitrogen atom and C-3 being “down”, and not, as in other investigated cases, , a half-chair conformation, i.e., with the nitrogen atom “up” and C-3 “down”. This led to unexpected cross-peaks in the NOESY spectra, which seemed to be contradictory to the ones anticipated for 4b and 5 regarding the initially assumed half-chair confirmation of their tetrahydroisoquinoline portions.…”

A Near-Complete Series of Four Atropisomeric Jozimine A2-Type Naphthylisoquinoline Dimers with Antiplasmodial and Cytotoxic Activities and Related Alkaloids from Ancistrocladus abbreviatus

“…This “invention” was achieved by using the same presumed monocyclic hexaketide precursor 11 , which leads to the naphthalene portion 12 (by two aldol condensation steps) and, in parallel, to the isoquinoline part 13 (by an aldol condensation followed by a nitrogen incorporation). These two bicyclic molecular portions are then joined together by phenol-oxidative coupling . Thus, the naphthylisoquinolines that are found in Dioncophyllaceae plants are probably the phylogenetically “oldest”, all lacking an oxygen function at C-6 (which, in the corresponding C-7 position in the naphthalene, is always missing, too) and throughout with R -configuration.…”

Ancistrolikokines E–H and related 5,8′-coupled naphthylisoquinoline alkaloids from the Congolese lianaAncistrocladus likokowith antiausterity activities against PANC-1 human pancreatic cancer cells

“…4,5 These secondary metabolites are the rst natural polyketide-derived isoquinoline alkaloids since not only the naphthalene part, but also the isoquinoline moiety originates from acetate-malonate units. [6][7][8] Depending on their individual structures, they display pronounced antiplasmodial, [9][10][11][12] antitrypanosomal, 9,13,14 antileishmanial, 9,[14][15][16] antileukemic, [17][18][19] or anti-HIV activities. 20,21 Previous phytochemical investigations on the roots and leaves of A. likoko had led to the isolation of six naphthylisoquinoline alkaloids, 22,23 viz., korupensamine A (1a), the ancistrolikokines A-D (2-4 and 6), and ancistroealaine A (7), along with the biosynthetically related tetralone cis-isoshinanolone (8) (Fig.…”