Comparative evaluation of a Pictet–Spengler protocol in microwave-assisted conversions of tryptamine with aryl- and carboxyaryl aldehydes: role of ring strain in cyclocondensation of the primarily formed carboxyaryl-substituted β-carbolines

2,3-Dihydroferroceno[3,4]pyrrolo[2,1-b]thiazol-5(8b)-ones: Synthesis, Structure and DFT Study on the Mechanism of Chemo- and Diastereoslective Annulations of (Sp)-2-Formylferrocenecarbonyl Fluoride and (Sp)-2-Formylferrocenecarboxylic Acid

“…Scheme 2 ). Thus, after heating at reflux in acetic acid containing boric acid for 6 h, representing the conditions we have successfully used to promote Biginelli reactions [ 36 ] and Pictet-Spengler condensations [ 37 ], this amide was recovered a with retained structure in 54% yield from the reaction mixture by means of an aqueous workup. The resistance of 13 to cyclocondensation was rationalized by comparative DFT studies performed by B3PW91 functional [ 38 ] employing a DGTZVP basis set [ 39 ].…”

Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

“…Prompted by the aforementioned highly promising precedents, in the frame of our ongoing research aimed at identification of novel leads including ferrocene hybrids [22][23][24][25][26][27][28][29] we envisaged atryptamine-and tryptophan-based synthesis, detailed structural analysis and preliminary in vitro evaluation of 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2',3':3,4]pyrido [1,2-c]quinazolines (I), 5,5b,17,18-tetrahydroindolo [2',3':3,4]pyrido [1,2-c]isoindolo[2,1-a]quinazolin-11(15bH)-ones (II), and (Sp)-2-formyl-1-ferrocenecarboxylate-derived 5,5b, 11,14b,16,17- A straightforward retrosynthetic analysis of pentacycles type I set up an obvious synthetic pathway starting with a Pictet-Spengler (PS) annelation involving tryptophan-based precursors and Molecules 2020, 25, 1599 3 of 25 2-nitrobenzaldehyde followed by nitro group reduction and subsequent aldehyde-mediated cyclisation of the resulting 2-aminophenyl-substituted β-carboline framework to construct the targeted pentacyclic products (Scheme 1). Accordingly, tryptamine (1) was first converted into the nitrophenyl derivative 3 by an efficient PS protocol using an acetic acid/boric acid system at reflux temperature to promote the reaction [30] which practically went to completion within 4 h and allowed the isolation of the product as a racemic mixture in 85% yield. The analogous reaction of the methyl ester of l-tryptophan (2), conducted under the same conditions, gave a hardly separable 1/2 mixture of cisand trans-diastereomer esters 4/C and 4/T.…”

“…A straightforward retrosynthetic analysis of pentacycles type I set up an obvious synthetic pathway starting with a Pictet-Spengler (PS) annelation involving tryptophan-based precursors and 2-nitrobenzaldehyde followed by nitro group reduction and subsequent aldehyde-mediated cyclisation of the resulting 2-aminophenyl-substituted β-carboline framework to construct the targeted pentacyclic products (Scheme 1). Accordingly, tryptamine (1) was first converted into the nitrophenyl derivative 3 by an efficient PS protocol using an acetic acid/boric acid system at reflux temperature to promote the reaction [30] which practically went to completion within 4 h and allowed the isolation of the product as a racemic mixture in 85% yield. The analogous reaction of the methyl ester of L-tryptophan (2), conducted under the same conditions, gave a hardly separable 1/2 mixture of cis-and trans-diastereomer esters 4/C and 4/T.…”