Synthesis and isolation of bromo‐β‐carbolines obtained by bromination of β‐carboline alkaloids

Abstract

β-Carbolines (1-5) undergo electrophilic aromatic substitution with N-bromosuccinimide under different experimental conditions. Although 6-bromo-nor-harmane (1a) obtained by bromination of nor-harmane (1) was isolated and fully characterized sometime ago, the other bromoderivatives of nor-harmane (1b-1e) and harmane (2a-2e) were partially described as part of the reaction mixtures. The preparation and subsequent isolation, purification and full characterization of 1b, 1c, 1d, 1e, 2a, 2b, 2c, 2d, 2e are reported (mp, R f , 1 H-nmr, 13 C-nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the bromoderivatives obtained from harmine (3a-3e), harmol (4a, 4b) and 7-acetylharmol (5a-5c). As brominating reagent N-bromosuccinimide and N-bromosuccinimide-silica gel in dichloromethane and in chloroform as well as the β-carboline -N-bomosuccinimide solid mixture have been used and their uses have been compared. Semiempirical AM1 and PM3 calculations have been performed in order to predict reactivity in terms of the energies of HOMO, HOMO-LUMO difference and in terms of the charge density of β-carbolines (1-5) and bromo-β-carbolines (1a-1e, 2a-2e, 3a-3e, 4a, 4b, 5a, 5b and 5c) (Scheme 1). Theoretical and experimental results are discussed briefly.

Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

“…First, harmine was brominated with N -bromosuccinimide in dichloromethane to obtain 8-bromo-harmine ( 7 ). The chemical shifts and intensities of the signals observed in the 1 H and 13 C NMR spectra (Figures S25–S27) are consistent with literature reports . Next, 7 was reacted under Suzuki conditions with vinylboronic acid pinacol ester in dioxane to give 8-vinyl-harmine ( 8 ).…”

“…The chemical shifts and intensities of the signals observed in the 1 H and 13 C NMR spectra (Figures S25−S27) are consistent with literature reports. 49 Next, 7 was reacted under Suzuki conditions with vinylboronic acid pinacol ester in dioxane to give 8-vinyl-harmine (8). In the 1 H NMR spectrum, three additional doublet-of-doublet signals were detected at 5.58, 6.20, and 7.27 ppm, originating from the three protons of the vinyl group (Figures S28 and S29).…”

β-Carboline derivatives as novel antivirals for herpes simplex virus

“…Norharmane, harmane, harmine, harmaline, 6-methoxy-harmane and Acyclovir (Sigma-Aldrich Co.) were of the highest purity available (>98%). Non-commercial derivative synthesis was described previously (purity >98%) [16][17][18][19]. Stock solutions of βCs were prepared in pH 2 sterile ultrapure water [11,20] and diluted (10%, vol/vol) to working concentrations in DMEM.…”

6‐Aryl‐Substituted Harmanium Derivatives as Light‐Up Probes for Fluorimetric DNA Detection and Staining of Eukaryotic Cells

“…The substituted harmane derivatives 3 a , 3 g – h were synthesized in 49–94 % yield with a Suzuki‐Miyaura coupling reaction [14] of 6‐bromoharmane ( 1 ) [15] with the arylboronic acids 2 a – h (Scheme 1). The literature‐known compounds 3 b – f were directly used for the next reaction step after column‐chromatographic pre‐purification [16] .…”