Stereospecific synthesis of -1,3-disubstituted-1,2,3,4-tetrahydro β-carbolines

The Pictet-Spengler condensation: a new direction for an old reaction

“…Following the initial assignment of stereochemistry attempts were made to corroborate the findings by another method. Chemical correlation of the cis isomer (via cyclization) was not possible, however, Ungemach et al 76 had reported earlier that IVb-benzyltryptophan methyl ester (21) reacted with either salicylaldehyde (43), glyoxal diethyl acetal (32), or propionaldehyde (68) to provide only the trans-1,3-disubstituted /3-carboline (e.g. 65, illustrated in Scheme 4).…”

Synthesis and Molecular Modeling of Novel Tetrahydro-β-carboline Derivatives with Phosphodiesterase 5 Inhibitory and Anticancer Properties

“…Conversely, an allyl ester favors the formation of the cis isomer upon reaction with an aldehyde. 18–21 We found that an aromatic aldehyde with bulky substituents at positions 2 and 6 of the benzene ring favors the formation of the cis isomer upon reaction with tryptophan methyl ester, probably due to restricted rotation. The Pictet–Spengler reaction was carried out at room temperature under nonstereospecific conditions.…”

“…As expected, the kinetics were in favor of the cis isomer. 18–21 Thus, the formation of diastereomers 3 , 5 , and 7 exceeded the formation of diastereomers 4 , 6 , and 8 , respectively, with % de = 11%, 27%, and 25%, respectively, meanwhile, for the isomers 1 and 9 , there was no preferentiality relative to 2 and 10. …”

Total Synthesis and Antibacterial Activity Evaluation of Griseofamine A and 16-epi-Griseofamine A

“…Selective prenylation of intermediate D could be achieved through the Suzuki–Miyaura cross-coupling reaction described by Buchwald, which would allow the highly α-selective coupling of 3,3-dimethyl allylboronate with an aryl bromide to afford a linear prenylated product with excellent regioselectivity − An appropriate modification was made in our study; that is, a p -methoxybenzyl group (PMB) was used instead of the benzyl group used in Cook’s method due to its tolerance of various harsh conditions and facile removal by cerium ammonium nitrate (CAN). Finally, intermediate E could be obtained from l -4-bromo tryptophan methyl ester and p -anisaldehyde via a reductive amination.…”

“…In most cases, the activities of griseofamine A and 16-epi-griseofamine A were slightly weaker than that of CIP. However, in the cases of MRSA (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and MRSE , both compounds exerted antibacterial activities significantly higher than that of CIP (entries 5 and 8, respectively). In addition, E. faecium and vancomycin-resistant E. faecium were not sensitive to CIP (MIC values of 64 and 128 μg/mL, respectively), whereas our compounds exhibited potential inhibitory activity toward these strains with MIC values of 16 μg/mL for griseofamine A and 8 μg/mL for 16-epi-griseofamine A (entries 13 −15).…”