Isoreserpiline

Extraction of the aerial part of Rinorea yaundensis has led to the isolation of a new monoterpene indole alkaloid (1) along with 10 known compounds (2-11) for the first time from this plant. Their structures were determined by HRMS and NMR spectroscopic analyses as yaundentine hydrochloride (1), Nb-oxide of iso-reserpiline (2), iso-reserpiline (3), iso-carapanaubine (4), lichenxanthone (5), stigmastane-3,6-dione (6), methyl β-orcinol carboxylate (7), β-sitosterol-3-O-β-D-glucoside (8), betulinic acid (9), ursolic acid (10) and benzoic acid (11) while the stereochemistry and absolute configuration of 1 was confirmed by single crystal x-ray crystallography and circular dichroism CD spectrum. Yaundentine hydrochloride (1) exhibited pronounced antioxidant, urease and lipoxygenase inhibitory activities with IC50 values of 35.6 ± 0.23, 20.3 ± 0.58 and 29.6 ± 0.77 µM, respectively. Compound 1 also showed good antimicrobial activity against some Gram positive and negative bacteria.

Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10-methoxy tetrahydroalstonine (1), isoreserpiline (2), 10 and 11 demethoxyreserpiline (3), reserpiline (4), serpentine (5), ajmaline (6), ajmalicine (7), yohimbine (8), and α-yohimbine (9) was evaluated using microbroth dilution assay. Further, α-yohimbine (9) was chemically transformed into six semisynthetic derivatives (9A-9F), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E. coli strains CA8000 and DH5α were also evaluated. The IA 1, 2, 4, 5, 9 and the derivative 9F showed eightfold reduction in the MIC of NAL against the DH5α and four- to eightfold reduction against CA8000. These alkaloids also reduced MIC of another antibiotic, tetracycline up to 8folds, against the MDREC-KG4, a multidrug-resistant clinical isolate of E. coli. Mode of action study of these alkaloids showed efflux pumps inhibitory potential, which was supported by their in silico binding affinity and downregulation of efflux pump genes. These results may be of great help in the development of cost-effective antibacterial combinations for treating patients infected with multidrug-resistant Gram-negative infections.

pH-zone-refining centrifugal partition chromatography was successively applied in the large-scale separation of close R(f) antipsychotic indole alkaloids directly from CHCl(3) fraction of Rauwolfia tetraphylla leaves. Two experiments with increasing mass from 500 mg to 3 g of crude alkaloid extracts (1C) of R. tetraphylla were carried out in normal-displacement mode using a two-phase solvent system composed of methyl tert-butyl ether/ACN/water (4:1:5, v/v/v) where HCl (12 mM) was added to the lower aqueous stationary phase as a retainer and triethylamine (5 mM) to the organic mobile phase as an eluter. The two centrifugal partition chromatography separations afforded a total of 162.6 mg of 10-methoxytetrahydroalstonine (1) and 296.5 mg of isoreserpiline (2) in 97% and 95.5% purity, respectively, along with a 400.9 mg mixture of α-yohimbine and reserpiline (3 and 4). Further, this mixture was resolved over medium pressure LC using TLC grade silica gel H (average particle size 10 μm), which afforded 160.4 mg of α-yohimbine (3) and 150.2 mg of reserpiline (4) in >95% purities. The purity of the isolated antipsychotic alkaloids was analyzed by high-performance LC and their structures were characterized on the basis of their 1D, 2D NMR and electrospray ionization-mass spectroscopic data.