Convenient synthesis of 1-aryl-9H-β-carboline-3-carbaldehydes and their transformation into dihydropyrimidinone derivatives by Biginelli reaction

1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

“…[59] Abranyi-Balogh et al also describedasimilarf our-step synthesis of b-carboline-3-carbaldehydes (158)s tartingf rom racemic tryptophan methyl ester through aP ictet-Spengler cyclization reactionw ith aromatic carbaldehydes under acidic conditions, followed by 2-iodoxybenzoic acid (IBX)-mediated dehydrogenation of tetrahydro-b-carbolines (155)a nd subsequent reduction of the ester moiety in compound 156 with NaBH 4 to afford an alcohol (157). [60] Finally,o xidation of compound 157 with MnO 2 afforded the 1-aryl-9H-b-carboline-3-carbaldehydes (158)i n3 0-57 %y ield, as shown in Scheme 54. [60] The same group demonstrated the applicability of these versatile building blocks (158)for aBiginelli reaction, as shown in Scheme 55.…”

“…[60] Finally,o xidation of compound 157 with MnO 2 afforded the 1-aryl-9H-b-carboline-3-carbaldehydes (158)i n3 0-57 %y ield, as shown in Scheme 54. [60] The same group demonstrated the applicability of these versatile building blocks (158)for aBiginelli reaction, as shown in Scheme 55. Thus, the b-carboline-3-carbaldehydes (158)w ere treated with various b-diketones or b-keto esters and urea in the presence of NiCl 2 ·6H 2 Ot os moothly generate the b-carboline-substituted dihydropyrimidine derivatives (159)a tt he C3 positioni nm oderate-to-excellent yields.…”

“…The side product was aK noevenagel-type by-product, with E stereochemistry across the double bond, and it wasu nable to react with urea to give the anticipated dihydropyrimidines (159). [60] Kamal et al designeda nd synthesized ac lass of C3-linked b-carbolineÀchalcone (163)a nd b-carbolineÀ(N-acetyl)-pyrazole derivatives (164)f rom 3-formyl-9H-carbolines (158)a nd evaluated their anticancer activity (Scheme 57). [61] These new hybrid molecules showeds ignificant cytotoxic activity,w ith IC 50 values from < 2.0 to 80 mm.…”

“…More recently,L iu et al described the synthesiso fN-methyl b-carboline-3-carbaldehydes (168)b yu sing as lightly modified procedure of that first reported by Abranyi-Balogha nd coworkers. [60] This synthesis was accomplished by using aP ictet-Spengler condensation reactiono fl-tryptophan methyl ester, which wasg enerated from l-tryptophan, with diversely substituted carbaldehydes, followed by oxidation with trichloroisocynuric acid (TCCA) to afford b-carboline derivatives 162.Furthermore, N-methylation with methyl iodide,f ollowedbyreduction of the ester moiety( 167)w ith LiAlH 4 and oxidation of resulting carbinolw ith MnO 2 ,f urnished the N-methylated b-carboline-3-carbaldehydes (168)i n8 4-98 %y ield, as shown in Scheme59. [63] Bai and co-workers reported the first synthesis of bis-b-carbolines( N-oxide esters, alcohols, acetates, and benzyloxy derivatives) and demonstrated their application as catalysts for asymmetrica llylation reactions.…”

“…Synthesis of dimeric b-carboline derivatives as anticancer agents.Scheme22. Synthesis of C1-imidazo[1,2-a]azine-substituted b-carboline conjugates(59)(60).Scheme23. Reactionmechanism for the formation of b-carboline-imidazo[1,2-a]azines.…”