Carbolines. Part 2: Comparison of some of the properties of α-, γ-, and δ-carbolines (Review)

Abstract

Published data on the chemical and biological properties of a-, g-, and d-carbolines are reviewed.Key words: Pyridoindoles (carbolines), chemical and biological properties of carbolines, pK a values of carbolines.Continuing our studies of the properties of carbolines [1], the present study reviews published data on the properties of a-, g-, and d-carbolines. Compounds belonging to different classes of carboline derivatives include many substances with marked biological activity [2, 3].The chemical and physicochemical properties of carbolines have as yet received only fragmentary and insufficient study.The ionization constants of a number of carbolines have been reported [4]. pK a values reflecting the ability of a proton to attach to the pyridine nitrogen atom were obtained, along with constants showing the extent of deprotonation of the indole NH group in carbolines. Table 1 shows that there are significant variations in the ionization constant depending on the structures of the carbolines studied.Information obtained from studies of ionization constants are important for comparing different carbolines. In relation to basicity (protonation of the pyridine nitrogen), it is important to note that the most basic compound in this series is g-carboline. This appears to be due to the greatest level of stabilization of the pyridinium cation due to delocalization of the positive charge by the electron pair of the indole nitrogen:The lowest level of basicity of a-carboline is probably associated with the appearance in the corresponding cation of non-binding interactions between the protons of the pyridinium and indole fragments which destabilize the forming cation.The greatest acidity of g-carboline probably arises by a similar mechanism (increased stabilization of the anion). 389 0091-150X/11/4507-0389

Donor N‐Substitution as Design Principle for Fast and Blue Luminescence in Carbene‐Metal‐Amides

“…These results indicate that Aza‐1 and Aza‐3 carbazoles are less efficient electron donors in CMA complexes than Aza‐2 and Aza‐4 carbazoles. [ 36 ] The 3,6‐Diaza complex shows the highest oxidation potential, with an E p value of +1.04 V, which is expected due to presence of two π‐deficient pyridine rings, thus indicating that the 3,6‐diazacarbazole moiety is the weakest electron donor in the CMA series. The resulting HOMO energy values and bandgaps increase in the order CMA1 (−5.61 eV), 1 Aza‐2 and Aza‐4 (−5.74 eV), Aza‐1 and Aza‐3 (−5.81 eV), and 3,6‐Diaza (−6.22 eV, Table S13, Supporting Information).…”

Recent Advances in the Synthesis of β-Carboline Alkaloids

“…This was followed by the Knoevenagel condensation of 353 with dimethyl malonate to afford the α,β-unsaturated malonate 354 . Using precursor 354 in the reaction with Yb(OTf) 3 , a Lewis acid-catalyzed [ 1 , 4 ]-hydride transfer and Mannich-type cascade cyclization was performed, which resulted in compound 355 containing the appropriate E-ring. The D-ring with the C14=C15 double bond was installed via alkene formation through diastereoselective ring-closing metathesis (from 355 to 358 ).…”

“…Carbolines are a remarkable family of heterocyclic natural products, with outstanding pharmacological potential. They are determined by their tricyclic, pyridine-fused indole framework (where the rings are identified as A, B and C), and classified according to the degree of saturation (fully saturated: 1,2,3,4-tetrahydro; partially saturated: 3,4-dihydro; and unsaturated β-carbolines) and the position of the N-atom in the C-ring as α-, β-, γ-or δ-carbolines ( Figure 1) [1,2]. β-Carboline alkaloids are widely distributed in nature including various plants, foodstuffs, marine creatures, insects, mammals as well as human tissues and body fluids.…”

A New Route to α-Carbolines Based on 6π-Electrocyclization of Indole-3-alkenyl Oximes

“…4,5 Nevertheless there are some important examples such as the naturally occurring anticancer compounds grossularine-1 and -2 6−9 and the neuronal cell protective agent mescengricin (Figure 1). 10 In the medicinal chemistry arena, α-carbolines such as the GABA modulator, 11 and the inhibitor of microsomal triglyceride transport protein implitapide, 12,13 have also been widely studied.…”

“…In contrast to β-carbolines that are widely represented among natural products and synthetic bioactive compounds, − α-carbolines (pyrido[2,3- b ]indoles) are considerably less well investigated. , Nevertheless there are some important examples such as the naturally occurring anticancer compounds grossularine-1 and -2 − and the neuronal cell protective agent mescengricin (Figure ) . In the medicinal chemistry arena, α-carbolines such as the GABA modulator, and the inhibitor of microsomal triglyceride transport protein implitapide, , have also been widely studied.…”