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.
