“…S3 in the Supplementary Material). For the (10R*,10aS*)-isomer (10), there are three minima for the C10b-C10 dihedral at ,142-1448. For the (10R*,10aR*)-isomer (12), similarly three minima are seen but the dihedral ranges from À12 to À208.…”
Section: Resultsmentioning
confidence: 99%
“…[9] Since then, there have been sporadic reports on PictetSpengler reactions between various aldehydes and ketones and histamine, histidine or histinol. [10] Notably, these reactions are generally reported as base-catalysed, probably going through a mechanism like that shown in Fig. 3.…”
The diastereoselective Pictet-Spengler reaction of aminopropyl-2-aminoimidazole with enantiopure aldehydes has been investigated. With amino acid-derived aldehydes, anti stereochemistry is favoured, with a diastereoselectivity up to 92 % achievable. The absolute stereochemistry of the products was determined through synthesis of a rigid derivative and from NMR data in combination with molecular modelling. The diastereoselectivity was shown to be dependent on the steric bulk of the amino acid side chain and independent of the nitrogen protecting group. Lewis acids catalysed the reaction but did not affect the diastereoselectivity.
“…S3 in the Supplementary Material). For the (10R*,10aS*)-isomer (10), there are three minima for the C10b-C10 dihedral at ,142-1448. For the (10R*,10aR*)-isomer (12), similarly three minima are seen but the dihedral ranges from À12 to À208.…”
Section: Resultsmentioning
confidence: 99%
“…[9] Since then, there have been sporadic reports on PictetSpengler reactions between various aldehydes and ketones and histamine, histidine or histinol. [10] Notably, these reactions are generally reported as base-catalysed, probably going through a mechanism like that shown in Fig. 3.…”
The diastereoselective Pictet-Spengler reaction of aminopropyl-2-aminoimidazole with enantiopure aldehydes has been investigated. With amino acid-derived aldehydes, anti stereochemistry is favoured, with a diastereoselectivity up to 92 % achievable. The absolute stereochemistry of the products was determined through synthesis of a rigid derivative and from NMR data in combination with molecular modelling. The diastereoselectivity was shown to be dependent on the steric bulk of the amino acid side chain and independent of the nitrogen protecting group. Lewis acids catalysed the reaction but did not affect the diastereoselectivity.
“…DL-3-Amino-4-(4-imidazolyl)-2-butanone dihydrochloride and DL-3-amino-4-phenyl-2-butanone hydrochloride were synthesized via the Dakin-West reaction of L-histidine or L-phenylalanine with acetic anhydride (Smissman & Weiss, 1971). L-Histidine was cyclized with formaldehyde, and histamine was cyclized with benzaldehyde in base-catalyzed Pictet-Spengler reactions (Neuberger, 1944;Stocker et al, 1966). Synthesized products were obtained as crystalline solids and exhibited the expected nuclear magnetic resonance spectra.…”
L-Histidine methyl ester inactivates histidine decarboxylase in a time-dependent manner. The possibility was considered that an irreversible reaction between enzyme and inhibitor occurs [Recsei, P. A., & Snell, E. E. (1970) Biochemistry 9, 1492-1497]. We have confirmed time-dependent inactivation by histidine methyl ester and have investigated the structure of the enzyme-inhibitor complex. Upon exposure to either 8 M guanidinium chloride or 6% trichloroacetic acid, unchanged histidine methyl ester is recovered. Formation of the complex involves Schiff base formation, most likely with the active site pyruvyl residue [Huynh, Q. K., & Snell, E. E. (1986) J. Biol. Chem. 261, 4389-4394], but does not involve additional irreversible covalent interaction between inhibitor and enzyme. Complex formation is a two-step process involving rapidly reversible formation of a loose complex and essentially irreversible formation of a tight complex. For the formation of the tight complex, Ki = 80 nM and koff = 2.5 X 10(-4) min-1. Time-dependent inhibition was also observed with L-histidine ethyl ester, L-histidinamide, and DL-3-amino-4-(4-imidazolyl)-2-butanone. No inactivation was observed with glycine methyl ester or histamine. We propose that in the catalytic reaction the carboxyl group of the substrate is in a hydrophobic region. The unfavorable interaction between the carboxylate group and the hydrophobic region facilitates decarboxylation [Crosby, J., Stone, R., & Liehard, G. E. (1970) J. Am. Chem. Soc. 92, 2891-2900]. With histidine methyl ester this unfavorable interaction is no longer present; hence, there is tight binding.(ABSTRACT TRUNCATED AT 250 WORDS)
“…For the last ∼100 years, the Pictet−Spengler reaction has been widely used for C−C bond formation in ring systems referred to as tetrahydro-β-carbolines (THBCs) and tetrahydroisoquinolines (THIQs). However, despite being an attractive strategy, its application is limited to only the following three amine prototypes: Trp/tryptamine, His/histamine, and dopamine/tyramine . A typical Pictet−Spengler reaction involves condensation of an aldehyde with amine (Trp or dopamine) to form an imine, which is often activated by Bronsted acids .…”
mentioning
confidence: 99%
“…Final cyclization between a sufficiently reactive aromatic moiety and activated iminium ion results in a new carbon−carbon bond, forming a heterocyclic ring (Figure ). In contrast, alkaline catalyst is used for Pictet−Spengler reaction involving His/histamine derived from imidazoles (Figure ). 3d,e 1 Typical acid-catalyzed Pictet−Spengler reaction. 2 Typical base-catalyzed Pictet−Spengler reaction.…”
A novel strategy for the Pictet-Spengler reaction is reported. Our strategy involves reaction of arylamines, linked to the N-1 of disubstituted imidazoles, with aldehydes in the presence of p-TsOH. The iminium ion generated in situ undergoes C-C bond formation with the C-5 of the imidazoles to furnish triazabenzoazulenes as a novel heterosystem. Our strategy differs from conventional Pictet-Spengler reaction since the latter utilizes only aliphatic amines in which the amine functionality is linked to a C instead of N of the activated aromatic moiety.
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