Diastereotopic synthesis of 1- and 1,1-substituted 4-phenyl-2,3,4,9-tetrahydro-1H-β-carbolines

Abstract

547.759.3 V. N. Azev, 2 and V. V. Kachala 3A diastereotopic Pictet-Spengler reaction was performed to form previously unknown 1-and 1,1-substituted 4-phenyl-β-carbolines based on β-phenyltryptamine, aldehydes of various structure, and isatins. It has been demonstrated that the predominant diastereomers of the prepared β-carbolines have the (R*,R*) configuration. The diasteroselectivity (de) of the reaction varies from 44 to 88%.The Pictet-Spengler reaction, which occurs in plants and in humans, leads to the formation of various derivatives including isoquinoline and β-carboline.Some very simple alkaloids containing the β-carboline structural moiety and belonging to the harmane group are found in medicinal plants such as Passiflora fluidum [1], P. edulis, P. incarnata, Bansteriopsis caapi [2], and Peganum harmala [3], Zygophylaceae. They are used in traditional medicine to treat asthma, jaundice, and other diseases [3,4]. Harmaline is a known MAO inhibitor and powerful serotonin antagonist [5]. Harmane alkaloids have been detected in food plants [2] such as soy, rye, wheat, rice, barley, mushrooms, grape juice, wine [6], charred insects, and cigarette smoke. It has been reported that alcohol increases the harmane content in the brain and urine [7].Cytotoxic effects of harmane alkaloids have also been found [8]. These alkaloids are reported to affect the cardiovascular system [9, 10] and to have a hypotensive effect [10].The harmane alkaloids include also eleagnine [(1R)-1-methyl-2,3,4,9-tetrahydro-1H-β-carboline]. A synthesis of the racemate of eleagnine (1a) using the Pictet-Spengler reaction based on tryptamine (1) and acetaldehyde was previously proposed [11].Much later eleagnine was biosynthesized [12] and synthesized enantioselectively [13,14] and (1S)-1-methyl-2,3,4,9-tetrahydro-1H-β-carboline was synthesized enantioselectively (ee > 98%) [15]. The reaction proceeded through the formation of two diastereomers with subsequent fractional crystallization of one of them and removal of a sulfamide, which was known to be chiral.Recently the solid-phase chemistry of indole is rapidly developing with the Pictet-Spengler reaction being carried out on a polymeric support to synthesize 1,3-disubstituted β-carbolines. Diastereoselectivities (de) of 8-52% have been obtained from tryptophan [16][17][18][19][20][21][22][23][24][25]. It depended on the presence of a substituted nitrogen in the indole ring [20].Based on this, we carried out diastereotopic syntheses of previously unknown 4-phenyl-1-and 1,1-substituted β-carboline derivatives using the Pictet-Spengler reaction. The starting materials were β-phenyltryptamine (1) as the racemate and aliphatic, aromatic, and heterocyclic aldehydes.

Synthesis of 4-phenyl-1-(2-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline

“…3-(2-Nitro-1-phenylethyl)-1H-indole [7] (26.6 g, 0.1 mol) dissolved in alcohol (94%, 100 mL) and freshly prepared Raney nickel (1 g) were boiled, treated with hydrazine hydrate (1 mol) in alcohol (94%, 100 mL), and boiled for 60 h. If the boiling stopped, a new portion of catalyst was added. The solution was filtered.…”

“…We demonstrated that the Pictet-Spengler reaction can be made diastereospecific by using β-phenyltryptamine (1) and various carbonyl compounds as starting materials [7][8][9][10][11]. Herein the possibility of forming and preparing a diastereomeric excess of (1R * ,4R * )-4-phenyl-1-(2-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline using the Pictet-Spengler reaction and β-phenyltryptamine (1) and 2-thiophenecarbaldehyde (2) as starting materials was studied [12].…”

Synthesis of Quinolino[1,2-c]quinazolin-6-one Derivatives via Formal (4+2)-Cycloaddition of Alkenes to Quinazolinе-Derived N-Acyliminium Cations: An Experimental and Theoretical Study

“…Unless otherwise stated, all reagents were purchased from commercial suppliers and used as received. 5,7-Dibromoisatin 15 and 5,7-dichloroisatin 16 were prepared by halogenation of isatin with bromine and isocyanuric chloride, respectively. Isatoic anhydrides 1a-d were synthesized by oxidation of corresponding isatins with H 2 O 2 in glacial AcOH.…”

Russian olive (Elaeagnus angustifolia) as a herbal healer

“…Altogether, this plant with possible reduction of blood pressure and enhancing the recovery of I/R can be a good choice in cardiac diseases but more studies needed. 37,91 ROS production is one of the main mechanisms of myocardial dysfunction and necrosis after I/R. superoxide dismutase (SOD) enzymes can control the radical species or ROS in myocardium.…”