Alkaloids from Cephalotaxus lanceolata and Their Cytotoxicities

Abstract

A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D (1, 2, and 4, resp.), together with ten known alkaloids, 3 and 5-13. The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, and HR-ESI-MS, and single-crystal X-ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK-BR-3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines.

Integrating yeast chemical genomics and mammalian cell pathway analysis

“…Interestingly, by merging the chemical-genetic profiles of FH535 and 3305-2 G4 and weighting the interaction scores to emphasize the overlap between their profiles, we predicted direct target yeast genes (CDC73 and MRK1) whose human homologs are key players in Wnt signaling pathway which either bind to β-catenin directly to activate expression of target genes upon transduction of the signal into the nucleus (parafibromin, homolog of CDC73), or stimulate cytoplasmic degradation of β-catenin by phosphorylation (GSK-3, homolog of MRK1). Furthermore, 3305-2 G4 is a known natural compound (drupacine) that is capable of suppressing cancer cell growth in vitro [51]. Whether this effect is related to Wnt/β-catenin signaling pathway remains to be explored.…”

Collective Asymmetric Total Synthesis of C‐11 Oxygenated Cephalotaxus Alkaloids

“…[13c-e] Fort he high diastereoselectivity during the N-quaternization with allylic electrophiles,o ne method employed ar igid nitrogen-fused bicyclic derivative H in which the nitrogen lone-pair electrons were forced to be located on the convex face. [13c] Unlike [5,5]-bicyclic compound H,t he designed [5,6]-bicyclic system E would be conformationally flexible.T hus,u nclear was the stereoselectivity in the Nquaternization of E which was critical to conserve the chirality of proline.…”

“…11‐Hydroxycephalotaxine ( 4 ), which is readily converted to 3 under acidic conditions, was also isolated from the same plant from which 3 was isolated [4] . To date, ten C‐11 oxygenated Cephalotaxus alkaloids have been isolated, including three ester derivatives of 3 ( 5 – 7 ) [5] and an N ‐oxide derivative cephalancetine B ( 8 ) [6] . A dimeric alkaloid cephalancetine D ( 9 ) [6] and pentacyclic cephalocyclidin A ( 10 ) [7] also belong to this subset.…”

Collective Asymmetric Total Synthesis of C‐11 Oxygenated Cephalotaxus Alkaloids

“…[13c-e] Fort he high diastereoselectivity during the N-quaternization with allylic electrophiles,o ne method employed ar igid nitrogen-fused bicyclic derivative H in which the nitrogen lone-pair electrons were forced to be located on the convex face. [13c] Unlike [5,5]-bicyclic compound H,t he designed [5,6]-bicyclic system E would be conformationally flexible.T hus,u nclear was the stereoselectivity in the Nquaternization of E which was critical to conserve the chirality of proline. Assuming success in our synthetic plan especially the chirality transferring transformations,s ynthetic efforts commenced with the preparation of the newly designed bicyclic proline derivative 16 and its N-alkylation partner cinnamyl halide 17 (Scheme 3a).…”

“…[4] To date,ten C-11 oxygenated Cephalotaxus alkaloids have been isolated, including three ester derivatives of 3 (5-7) [5] and an N-oxide derivative cephalancetine B(8). [6] Adimeric alkaloid cephalancetine D( 9) [6] and pentacyclic cephalocyclidin A (10) [7] also belong to this subset. Recently,torreyafargesine A (11)a nd 11-hydroxycephalotaxinone hemiketal (12)w ere identified from Torreya fargesii Franch as new members of the C-11 oxygenated subset.…”