Manoel T. Rodrigues

Novel Supramolecular Palladium Catalyst for the Asymmetric Reduction of Imines in Aqueous Media

A novel approach to the asymmetric reduction of dihydro-beta-carboline derivatives to the corresponding tetrahydro-beta-carbolines is described based on the supramolecular lyophilized complex formed from beta-cyclodextrin/imines as an enzyme mimetic and palladium hydride as the reducing agent. The methodology allowed us to develop a short and efficient preparation of (R)-harmicine and (R)-deplancheine alkaloids in high overall yields and ee of 89 and 90%, respectively.

Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles

The cyclopenta[b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta[b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form β-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding β-hydroxy-esters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta[b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles, via an intramolecular Friedel-Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antitumoral profile.

The Asymmetric Total Synthesis of (+)- and (-)-Trypargine via Noyori Asymmetric Transfer Hydrogenation

Uma sintese total e eficiente da (+) e (-)-tripargina, alcaloide b-carbolinico isolado da pele da ra africana K. Senegalensis, foi realizada em 6 etapas e 38% de rendimento global, a partir da triptamina, tendo como base a construcao do sistema b-carbolinico via reacao de BischlerNapieralski e a reducao enantiosseletiva do intermediario diidro-b-carbolinico via reacao de transferencia de hidrogenio assimetrica usando o protocolo de Noyori. A concise and efficient total synhesis of (+)- and (-)-trypargine (6 steps and 38% overall yield), a 1-substituted b-carboline guanidine alkaloid isolated from the skin of the African frog K. senegalensis, was developed based on the construction of the b-carboline moiety via BischlerNapieralski reaction and the enantioselective reduction of the dihydro-b-carboline intermediate

Crystal structure of 3-(3,4,5-tri-meth-oxy-phen-yl)-1,2,3,4-tetra-hydro-cyclo-penta[b]indole-2-carb-oxy-lic acid.

In the title compound, C21H21NO5, obtained from a Morita–Baylis–Hillman adduct, the hydrogenated five-membered ring adopts a shallow envelope conformation, with the C atom bearing the carboxylic acid substituent deviating by 0.237 (1) Å from the mean plane of the other four atoms (r.m.s. deviation = 0.007 Å). The dihedral angle between the fused ring system (all atoms; r.m.s. deviation = 0.057 Å) and the pendant trimethoxy benzene ring is 66.65 (3)°. The C atoms of the meta-methoxy groups lie close to the plane of the benzene ring [deviations = 0.052 (1) and −0.083 (1) Å], whereas the C atom of the para-methoxy group is significantly displaced [deviation = −1.289 (1) Å]. In the crystal, carboxylic acid inversion dimers generate R 2 2(8) loops. The dimers are connected by N—H⋯O hydrogen bonds, forming [011] chains. A C—H⋯O interaction is also observed.