Cis‐Diastereoselectivity in Pictet–Spengler Reactions of L‐Tryptophan and Electronic Circular Dichroism Studies

Abstract

The diastereoselective synthesis of optically active 1,3-disubstituted tetrahydro-β-carbolines using polar protic Pictet-Spengler cyclization of (S)-tryptophan methyl ester with five aldehydes RCHO (R═CH(3), C(2)H(5), C(3)H(7), C(4)H(9), and C(6)H(5)) was studied. As an alternate route, the cyclization of (S)-tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro-β-carboline carboxylic acids were also performed for comparison. (13)C NMR and electronic circular dichroism (ECD) studies and time-dependent density functional theory ECD calculations data established the relative 1,3 cis/trans and the absolute configuration (1S,3S/ 1R,3S) of the synthesized compounds. The solid-state and solution ECD study of the prepared compounds, supported by ECD calculation and X-ray data, afforded a reliable ECD method for the configurational assignment of 1,3-disubstituted tetrahydro-β-carbolines and revealed the stereochemical factors that determine the characteristic ECD data.

Strong Intermolecular Exciton Couplings in Solid‐State Circular Dichroism of Aryl Benzyl Sulfoxides

“…Therefore, the comparison between the solid‐state CD spectrum measured on a microcrystalline sample and that calculated using the X‐ray geometry as input structure would lead to the configurational assignment in a very efficient way, avoiding any conformational ambiguity. We have exploited this possibility in a so‐called solid‐state CD/TDDFT approach for the assignment of the absolute configuration of several organic compounds, mostly natural products . The advantages of this method are especially evident when very flexible and complex natural products are concerned, and repay well the necessary additional care to be put into solid‐state CD measurements to avoid spectral artifacts …”

“…We have exploited this possibility in a so-called solid-state CD/TDDFT approach for the assignment of the absolute configuration of several organic compounds, mostly natural products. 2,[43][44][45] The advantages of this method are especially evident when very flexible and complex natural products are concerned, 46 and repay well the necessary additional care to be put into solid-state CD measurements to avoid spectral artifacts. 3,[47][48][49][50] During the course of application of the solid-state CD/ TDDFT approach, an interesting theoretical question arose.…”

Dynamic Kinetic Resolution of Ethyl 1,2,3,4‐Tetrahydro‐β‐carboline‐1‐carboxylate: Use of Different Hydrolases for Stereocomplementary Processes

“…The ECD spectra computed at the various levels of theory for both sets of conformers gave good mirror‐image agreement with the experimental spectrum (Figure ) allowing the unambiguous elucidation of the absolute configuration of (–)‐ 2 as R . According to literature data for related β‐carboline derivatives, ECD is mainly governed by the helicity of the saturated six‐membered ring . In our case, however, the positive charge in the ring of the cationic form makes a substantial contribution to the electronic transition moment vector, which was estimated in different ways in the gas phase and solvent model.…”

Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe)

“…The indole alkaloid 1 was demonstrated to have a more potent antithrombotic activity than heparin. Tetrahydro-b-carbolines 2-4 could be produced through a Pictet-Spengler condensation of tryptophan with aldehydes or a-oxo acids [33]. Although the antiplatelet activity of one of the tetrahydro-b-carbolines has been reported [34], intravital microscopic technique to study thrombus formation in real time has enabled us to establish a role for this molecule in the regulation of thrombus formation in vivo.…”